PA R T I V

Learning and Developmental Disorders

OUTLINE

Chapter 48 Neurodevelopmental and Executive Function and

Dysfunction
Chapter 49 Attention-Deficit/Hyperactivity Disorder
Chapter 50 Dyslexia
Chapter 51 Math and Writing Disabilities
Chapter 52 Language Development and Communication Disorders
Chapter 53 Developmental Delay and Intellectual Disability
Chapter 54 Autism Spectrum Disorder
CHAPTER 48

Neurodevelopmental and Executive

Function and Dysfunction
Desmond P. Kelly, Mindo J. Natale

Terminology and Epidemiology

A neurodevelopmental function is a basic brain process needed for learning
and productivity. Executive function (EF) is an umbrella term used to describe
specific neurocognitive processes involved in the regulating, guiding,
organizing, and monitoring of thoughts and actions to achieve a specific goal.
Processes considered to be “executive” in nature include inhibition/impulse
control, cognitive/mental flexibility, emotional control, initiation skills, planning,
organization, working memory, and self-monitoring. Neurodevelopmental
and/or executive dysfunctions reflect any disruptions or weaknesses in these
processes, which may result from neuroanatomic or psychophysiologic
malfunctioning. Neurodevelopmental variation refers to differences in
neurodevelopmental functioning. Wide variations in these functions exist within
and between individuals. These differences can change over time and need not
represent pathology or abnormality.
Neurodevelopmental and/or executive dysfunction places a child at risk for
developmental, cognitive, emotional, behavioral, psychosocial, and adaptive
challenges. Preschool-age children with neurodevelopmental or executive
dysfunction may manifest delays in developmental domains such as language,
motor, self-help, or social-emotional development and self-regulation. For the
school-age child, an area of particular focus is academic skill development. The
Diagnostic and Statistical Manual of Mental Disorder, Fifth Edition (DSM-5)
classifies academic disorder within the group of neurodevelopmental disorders
as specific learning disorder (SLD) , with broadened diagnostic criteria
recognizing impairments in reading, written expression, and mathematics. In the
International Classification of Diseases, Tenth Edition (ICD-10),
neurodevelopmental disorders include specific developmental disorders of
scholastic skills with specific reading disorder, mathematics disorder, and
disorder of written expression. Dyslexia is categorized separately in ICD-10
under “Symptoms and Signs Not Elsewhere Classified.” Frontal lobe and
executive function deficit is also included in this category. Disorders of
executive function have traditionally been viewed as a component of attention-
deficit/hyperactivity disorder ( ADHD) , which is also classified in DSM-5 as
a neurodevelopmental disorder.
There are no prevalence estimates specifically for neurodevelopmental
dysfunction, but overall estimates for learning disorders range from 3–10% with
a similar range reported for ADHD. These disorders frequently co-occur. The
range in prevalence is likely related to differences in definitions and criteria used
for classification and diagnosis, as well as differences in methods of assessment.

Etiology and Pathogenesis

Neurodevelopmental and executive dysfunction may result from a broad range
of etiologic factors, including genetic, medical, psychological, environmental,
and sociocultural influences.
There is a high degree of heritability reported in learning and attention
disorders, with estimates ranging from 45–80%. Specific genes have been
identified that are associated with reading disorders, including the DYX2 locus
on chromosome 6p22 and the DYX3 locus on 2p12. Neuroimaging studies have
confirmed links between gene variations and variations in cortical thickness in
areas of the brain known to be associated with learning and academic
performance, such as the temporal regions. Chromosomal abnormalities can lead
to unique patterns of dysfunction, such as visual-spatial deficits in girls
diagnosed with Turner syndrome (see Chapter 98.4 ) or executive and language
deficits in children with fragile X syndrome (Chapter 98.5 ). Chromosome
22q11.2 deletion syndrome (velocardiofacial-DiGeorge syndrome; Chapter 98.3
) has been associated with predictable patterns of neurodevelopmental and
executive dysfunction that can be progressive, including a higher prevalence of
intellectual disability, as well as deficits in visual-spatial processing, attention,
working memory, verbal learning, arithmetic, and language.
Genetic vulnerabilities may be further influenced by perinatal factors,
including very low birthweight, severe intrauterine growth restriction, perinatal
hypoxic-ischemic encephalopathy, and prenatal exposure to substances such as
alcohol and drugs. Increased risk of neurodevelopmental and executive
dysfunction has also been associated with environmental toxins, including lead
(see Chapter 739 ); drugs such as cocaine; infections such as meningitis, HIV,
and Zika; and brain injury secondary to intraventricular hemorrhage,
periventricular leukomalacia, or head trauma. The academic effects of
concussion in children and adolescents, although usually temporary, have been
well characterized, including impaired concentration and slowed processing
speed. Repeated injuries have a much higher likelihood of long-term negative
neurocognitive effects.
Early psychological trauma may result in both structural and neurochemical
changes in the developing brain, which may contribute to neurodevelopmental
and executive dysfunction. Findings suggest that the effects of exposure to
trauma or abuse early in the developmental course can induce disruption of the
brain's regulatory system and may influence right hemisphere function with
associated risk for problems with information processing, memory, focus, and
self-regulation. Environmental and sociocultural deprivation can lead to, or
potentiate, neurodevelopmental and executive dysfunction, and numerous
studies have indicated that parent/caregiver executive functioning impacts the
development of EFs in offspring.
With regard to pathogenesis , investigations of neuroanatomic substrates have
yielded important information about the underlying mechanisms in
neurodevelopmental and executive dysfunction. Multiple neurobiologic
investigations have identified differences in the left parietotemporal and left
occipitotemporal brain regions of individuals with dyslexia compared to those
without reading difficulties (see Chapter 50 ). Studies have also described the
neural circuitry, primarily in the parietal cortex, underlying mathematical
competencies such as the processing of numerical magnitude and mental
arithmetic. The associations between executive dysfunction and the
prefrontal/frontal cortex have been well established, and insults to the frontal
lobe regions often result in dysfunction of executive abilities (e.g., poor
inhibitory control). Although the prefrontal/frontal cortex may be the primary
control region for EFs, there is considerable interconnectivity between the
brain's frontal regions and other areas, such as arousal systems (reticular
activating system), motivational and emotional systems (limbic system), cortical
association systems (posterior/anterior; left/right hemispheres), and input/output
systems (frontal motor/posterior sensory areas).
Core Neurodevelopmental Functions
The neurodevelopmental processes that are critical to a child's successful
functioning may best be understood as falling within core neurodevelopmental
domains . Notwithstanding such classification of domains, the clinical
distinctions often made regarding “cognitive” processes (e.g., intelligence, EF,
attention, language, memory) are relatively artificial because these brain
functions are highly integrated.

Sensory and Motor Function

Sensory development (e.g., auditory, visual, tactile, proprioceptive) begins well
before birth. This neurodevelopmental process is crucial in helping children
experience, understand, and manipulate their environments. Sensory
development progresses in association with environmental exposure and with the
development of other cognitive processes, such as motor development. Through
sensory experiences, children's brains mature as new neuronal pathways are
created and existing pathways are strengthened.
There are three distinct, yet related, forms of neuromotor ability: fine motor,
graphomotor, and gross motor coordination. Fine motor function reflects the
ability to control the muscles and bones to produce small, exact movements.
Deficits in fine motor function can disrupt the ability to communicate in written
form, to excel in artistic and crafts activities, and can interfere with learning a
musical instrument or mastering a computer keyboard. The term dyspraxia
relates to difficulty in developing an ideomotor plan and activating coordinated
and integrated visual-motor actions to complete a task or solve a motor problem,
such as assembling a model. Graphomotor function refers to the specific motor
aspects of written output. Several subtypes of graphomotor dysfunction can
significantly impede writing. Children who harbor weaknesses of visualization
during writing have trouble picturing the configurations of letters and words as
they write (orthographics), with poorly legible written output with inconsistent
spacing between words. Others have weaknesses in orthographic memory and
may labor over individual letters and prefer printing (manuscript) to cursive
writing. Some exhibit signs of finger agnosia and have trouble localizing their
fingers while they write, needing to keep their eyes very close to the page and
applying excessive pressure to the pencil. Others struggle producing the highly
coordinated motor sequences needed for writing, a phenomenon also described
as dyspraxic dysgraphia . It is important to emphasize that a child may show
excellent fine motor dexterity (as revealed in mechanical or artistic domains) but
very poor graphomotor fluency (with labored or poorly legible writing).
Gross motor function refers to control of large muscles. Children with gross
motor incoordination often have problems in processing “outer spatial”
information to guide gross motor actions. Affected children may be inept at
catching or throwing a ball because they cannot form accurate judgments about
trajectories in space. Others demonstrate diminished body position sense. They
do not efficiently receive or interpret proprioceptive and kinesthetic feedback
from peripheral joints and muscles. They are likely to evidence difficulties when
activities demand balance and ongoing tracking of body movement. Others are
unable to satisfy the motor praxis demands of certain gross motor activities. It
may be difficult for them to recall or plan complex motor procedures such as
those needed for dancing, gymnastics, or swimming.

Language
Language is one of the most critical and complex cognitive functions and can be
broadly divided into receptive (auditory comprehension/understanding) and
expressive (speech and language production and/or communication) functions.
Children who primarily experience receptive language problems may have
difficulty understanding verbal information, following instructions and
explanations, and interpreting what they hear. Expressive language weaknesses
can result from problems with speech production and/or problems with higher-
level language development. Speech production difficulties include oromotor
problems affecting articulation, verbal fluency, and naming. Some children have
trouble with sound sequencing within words. Others find it difficult to regulate
the rhythm or prosody of their verbal output. Their speech may be dysfluent,
hesitant, and inappropriate in tone. Problems with word retrieval can result in
difficulty finding exact words when needed (as in a class discussion) or
substituting definitions for words (circumlocution).
The basic components of language include phonology (ability to process and
integrate the individual sounds in words), semantics (understanding the meaning
of words), syntax (mastery of word order and grammatical rules), discourse
(processing and producing paragraphs and passages), metalinguistics (ability to
think about and analyze how language works and draw inferences), and
pragmatics (social understanding and application of language). Children who
evidence higher-level expressive language impediments have trouble
formulating sentences, using grammar acceptably, and organizing spoken (and
possibly written) narratives.
To one degree or another, all academic skills are taught largely through
language, and thus it is not surprising that children who experience language
dysfunction often experience problems with academic performance. In fact,
some studies suggest that up to 80% of children who present with a specific
learning disorder also experience language-based weaknesses. Additionally, the
role of language in executive functioning cannot be understated, since language
serves to guide cognition and behavior.

Visual-Spatial/Visual-Perceptual Function
Important structures involved in the development and function of the visual
system include the retina, optic cells (e.g., rods and cones), the optic chiasm, the
optic nerves, the brainstem (control of automatic responses, e.g., pupil dilation),
the thalamus (e.g., lateral geniculate nucleus for form, motion, color), and the
primary (visual space and orientation) and secondary (color perception) visual
processing regions located in and around the occipital lobe. Other brain areas,
considered to be outside of the primary visual system, are also important to
visual function, helping to process what (temporal lobe) is seen and where it is
located in space (parietal lobe). It is now well documented that the left and right
cerebral hemispheres interact considerably in visual processes, with each
hemisphere possessing more specialized functions, including left hemisphere
processing of details, patterns, and linear information and right hemisphere
processing of the gestalt and overall form.
Critical aspects of visual processing development in the child include
appreciation of spatial relations (ability to perceive objects accurately in space
in relation to other objects), visual discrimination (ability to differentiate and
identify objects based on their individual attributes, e.g., size, shape, color, form,
position), and visual closure (ability to recognize or identify an object even
when the entire object cannot be seen). Visual-spatial processing dysfunctions
are rarely the cause of reading disorders, but some investigations have
established that deficits in orthographic coding (visual-spatial analysis of
character-based systems) can contribute to reading disorders. Spelling and
writing can emerge as a weakness because children with visual processing
problems usually have trouble with the precise visual configurations of words. In
mathematics, these children often have difficulty with visual-spatial orientation,
with resultant difficulty aligning digits in columns when performing calculations
and difficulty managing geometric material. In the social realm, intact visual
processing allows a child to make use of visual or physical cues when
communicating and interpreting the paralinguistic aspects of language. Secure
visual functions are also necessary to process proprioceptive and kinesthetic
feedback and to coordinate movements during physical activities.

Intellectual Function
A useful definition of intellectual function is the capacity to think in the
abstract, reason, problem-solve, and comprehend. The concept of intelligence
has had many definitions and theoretical models, including Spearman's unitary
concept of “the g-factor,” the “verbal and nonverbal” theories (e.g., Binet,
Thorndike), the 2-factor theory from Catell (crystallized vs fluid intelligence),
Luria's simultaneous and successive processing model, and more recent models
that view intelligence as a global construct composed of more-specific cognitive
functions (e.g., auditory and visual-perceptual processing, spatial abilities,
processing speed, working memory).
The expression of intellect is mediated by many factors, including language
development, sensorimotor abilities, genetics, heredity, environment, and
neurodevelopmental function. When an individual's measured intelligence is >2
standard deviations below the mean (a standard score of <70 on most IQ tests)
and accompanied by significant weaknesses in adaptive skills, the diagnosis of
intellectual disability may be warranted (see Chapter 53 ).
Functionally, some common characteristics distinguish children with deficient
intellectual functioning from those with average or above-average abilities.
Typically, those at the lowest end of the spectrum (e.g., profound or severe
intellectual deficiencies) are incapable of independent function and require a
highly structured environment with constant aid and supervision. At the other
end of the spectrum are those with unusually well-developed intellect (“gifted”).
Although this level of intellectual functioning offers many opportunities, it can
also be associated with functional challenges related to socialization and learning
and communication style. Individuals whose intellect falls in the below-average
range (sometimes referred to as the “borderline” or “slow learner” range) tend to
experience greater difficulty processing and managing information that is
abstract, making connections between concepts and ideas, and generalizing
information (e.g., may be able to comprehend a concept in one setting but are
unable to carry it over and apply it in different situation). In general, these
individuals tend to do better when information is presented in more concrete and
explicit terms, and when working with rote information (e.g., memorizing
specific material). Stronger intellect has been associated with better-developed
concept formation, critical thinking, problem solving, understanding and
formulation of rules, brainstorming and creativity, and metacognition (ability to
“think about thinking”).

Memory
Memory is a term used to describe the cognitive mechanism by which
information is acquired, retained, and recalled. Structurally, some major brain
areas involved in memory processing include the hippocampus, fornix, temporal
lobes, and cerebellum, with connections in and between most brain regions. The
memory system can be partitioned into subsystems based on processing
sequences; the form, time span, and method of recall; whether memories are
conscious or unconsciously recalled; and the types of memory impairments that
can occur.
Once information has been identified (through auditory, visual, tactile, and/or
other sensory processes), it needs to be encoded and registered , a mental
process that constructs a representation of the information into the memory
system. The period (typically seconds) during which this information is being
held and/or manipulated for registration, and ultimately encoded, consolidated,
and retained, is referred to as working memory . Other descriptors include
short-term memory and immediate memory . Consolidation and storage
represent the process by which information in short-term memory is transferred
into long-term memory . Information in long-term memory can be available for
hours or as long as a life span. Long-term memories are generally thought to be
housed, in whole or in part, in specific brain regions (e.g., cortex, cerebellum).
Ordinarily, consolidation in long-term memory is accomplished in 1 or more of 4
ways: pairing 2 bits of information (e.g., a group of letters and the English sound
it represents); storing procedures (consolidating new skills, e.g., the steps in
solving mathematics problems); classifying data in categories (filing all insects
together in memory); and linking new information to established rules, patterns,
or systems of organization (rule-based learning).
Once information finds its way into long-term memory, it must be accessed. In
general, information can be retrieved spontaneously (a process known as free
recall ) or with the aid of cues (cued or recognition recall ). Some other
common descriptors of memory include anterograde memory (capacity to learn
from a single point in time forward), retrograde memory (capacity to recall
information that was already learned), and explicit memory (conscious
awareness of recall), implicit memory (subconscious recall: no awareness that
the memory system is being activated), procedural memory (memory for how
to do things), and prospective memory or remembering to remember .
Automatization reflects the ability to instantaneously access what has been
learned in the past with no expenditure of effort. Successful students are able to
automatically form letters, master mathematical facts, and decode words.

Social Cognition
The development of effective social skills is heavily dependent on secure social
cognition, which consists of mental processes that allow an individual to
understand and interact with the social environment. Although some evidence
shows that social cognition exists as a discrete area of neurodevelopmental
function, multiple cognitive processes are involved with social cognition. These
include the ability to recognize, interpret, and make sense of the thoughts,
communications (verbal and nonverbal), and actions of others; the ability to
understand that others' perceptions, perspectives, and intentions might differ
from one's own (commonly referred to as “theory of mind”); the ability to use
language to communicate with others socially (pragmatic language); and the
ability to make inferences about others and the environment based on contextual
information. It can also be argued that social cognition involves processes
associated with memory and EFs such as flexibility.

Executive Function
The development of EFs begins very early on in the developmental course (early
indications of inhibitory control and even working memory have been found in
infancy), matures significantly during the preschool years, and continues to
develop through adolescence and well into adulthood. Some studies suggest that
secure EF may be more important than intellectual ability for academic success
and have revealed that a child's ability to delay gratification early in life predicts
competency, attention, self-regulation, frustration tolerance, aptitude, physical
and mental health, and even substance dependency in adolescence and
adulthood. Conversely, deficits in other areas of neurodevelopment, such as
language development, impact EF.
Attention is far from a unitary, independent, or specific brain function. This
may be best illustrated through the phenotype associated with ADHD) (see
Chapter 49 ). Disordered attention can result from faulty mechanisms in and
across subdomains of attention. These subdomains include selective attention
(ability to focus attention on a particular stimulus and to discriminate relevant
from irrelevant information), divided attention (ability to orient to more than one
stimulus at a given time), sustained attention (ability to maintain one's focus),
and alternating attention (capacity to shift focus between stimuli).
Attention problems in children can manifest at any point, from arousal
through output. Children with diminished alertness and arousal can exhibit signs
of mental fatigue in a classroom or when engaged in any activity requiring
sustained focus. They are apt to have difficulty allocating and sustaining their
concentration, and their efforts may be erratic and unpredictable, with extreme
performance inconsistency. Weaknesses of determining saliency often result in
focusing on the wrong stimuli, at home, in school, and socially, and missing
important information. Distractibility can take the form of listening to
extraneous noises instead of a teacher, staring out the window, or constantly
thinking about the future. Attention dysfunction can affect the output of work,
behavior, and social activity. It is important to appreciate that most children with
attentional dysfunction also harbor other forms of neurodevelopmental
dysfunction that can be associated with academic disorders (with some estimates
suggesting up to 60% comorbidity).
Inhibitory control (IC) can be described as one's ability to restrain, resist,
and not act (cognitively or behaviorally/emotionally) on a thought. IC may also
be seen as one's ability to stop thoughts or ongoing actions. Deficits in this
behavioral/impulse regulation mechanism are a core feature of the combined or
hyperactive impulsive presentation of ADHD and have a significant adverse
impact on a child's overall functioning. In everyday settings, children with weak
IC may exhibit difficulties with self-control and self-monitoring of their
behavior and output (e.g., impulsivity), may not recognize their own errors or
mistakes, and often act prematurely and without consideration of the potential
consequences of their actions. In the social context, disinhibited children may
interrupt others and demonstrate other impulsive behaviors that often interfere
with interpersonal relationships. The indirect consequences of poor IC often lead
to challenges with behavior, emotional, and academic functioning and social
interaction (Table 48.1 ).

Table 48.1

Symptom Expression of Executive Dysfunction

EXECUTIVE FUNCTION
SYMPTOM EXPRESSION
DEFICIT
Disinhibition Impulsivity/poor behavioral regulation
Interrupts
“Blurts things out”
Shifting Problems with transitioning from one task/activity to another
Unable to adjust to unexpected change
Repeats unsuccessful problem-solving approaches
Initiation Difficulty independently beginning tasks/activities
Lacks initiative
Difficulty developing ideas or making decisions
Working memory Challenges following multistep instruction (e.g., only completes 1 of 3
steps)
Forgetfulness
Organization and planning Fails to plan ahead
Work is often disorganized
Procrastinates and does not complete tasks
“Messy” child
Self-monitoring Fails to recognize errors and check work
Does not appreciate impact of actions on others
Poor self-awareness
Affect control Experiences behavioral and emotional outbursts (e.g., tantrums)
Easily upset/frustrated
Frequent mood changes

Working memory (WM) can be defined as the ability to hold, manipulate,

and store information for short periods. This function is critical to be able to
complete multistep problems and more complex instructions and tasks. In its
simplest form, WM involves the interaction of short-term verbal and visual
processes (e.g., memory, phonologic, awareness, and spatial skills) with a
centralized control mechanism that is responsible for coordinating all the
cognitive processes involved (e.g., temporarily suspending information in
memory while working with it). Developmentally, WM capacity can double or
triple between the preschool years and adolescence. When doing math, a child
with WM dysfunction might carry a number and then forget what he intended to
do after carrying that number. WM is an equally important underlying function
for reading, where it enables the child to remember the beginning of a paragraph
when she arrives at the end of it. In writing, WM helps children remember what
they intend to express in written form while they are performing another task,
such as placing a comma or working on spelling a word correctly. WM also
enables the linkage between new incoming information in short-term memory
with prior knowledge or skills held in longer-term memory.
Initiation refers to the ability to independently begin an activity, a task, or
thought process (e.g., problem-solve). Children who present with initiation
difficulties often have trouble “getting going” or “getting started.” This can be
exhibited behaviorally, such that the child struggles to start on physical activities
such as getting out of bed or beginning chores. Cognitively, weaknesses in
initiation may manifest as difficulty coming up with ideas or generating plans. In
school, children who have poor initiation abilities may be delayed in or unable to
start homework assignments or tests. In social situations, initiation challenges
may cause a child to have difficulty beginning conversations, calling on friends,
or going out to be with friends.
Deficits in “primary” initiation are relatively rare and are often associated with
significant neurologic conditions and treatments (e.g., traumatic brain injury,
anoxia, effects of radiation treatment in childhood cancer). More often, initiation
deficits are secondary to other executive problems (e.g., disorganization) or
behavioral (e.g., oppositional/defiant behaviors), developmental (e.g., autism
spectrum disorder), or emotional (e.g., depression, anxiety) disorders.
Planning refers to the ability to effectively generate, sequence, and put into
motion the steps and procedures necessary to realize a specific goal. In real-
world settings, children who struggle with planning are typically described by
caregivers and teachers as being inept at independently gathering what is
required to solve a problem, or as unable to complete more weighty assignments.
Another common complaint is that these children exhibit poor time management
skills. Organization is an ability that represents a child's proficiency in
arranging, ordering, classifying, and categorizing information. Common daily
life challenges associated with organizational difficulties in childhood include
problems with gathering and managing materials or items. When children
struggle with organization, indirect consequences may include becoming
overwhelmed with information and being unable to complete a task or activity.
Effective organization is a vital component in learning (more specifically, in
memory/retention); many studies along with clinical experience have shown that
poor organization significantly impacts how well a child recalls information.
Planning and organizing depend on discrimination ability, which refers to the
child's ability to determine what is and is not valuable when trying to problem-
solve or organize.
 Emotional control is the ability to regulate emotions in order to realize goals
and direct one's behavior, thoughts, and actions. It has been well established that
affective/emotional states have an impact on many aspects of functioning.
Conversely, executive function or dysfunction often contributes to modulation or
affect. While emotional control is highly interrelated with different EFs (e.g.,
disinhibition, self-monitoring), separating it conceptually facilitates an
appreciation for and recognition of the often-overlooked role that a child's
emotional state plays in cognitive and behavioral functioning. Children with
weak emotional control may exhibit explosive outbursts, poor temper/anger
control, and oversensitivity. Clearly, understanding a child's emotional state is
vital to understanding its impact not only on executive functioning, but also on
functioning as a whole (e.g., socially, mentally, behaviorally, academically).
Any discussion involving emotional control should also recognize motivation
. Motivation/effort may be defined as the reason or reasons one acts or behaves
in a certain way. Less motivated children are less likely to engage and utilize all
their abilities. Such a disposition not only interferes with application of
executive skills, but also results in less than optimal performance and
functioning. The less success a child feels, the less likely the child is to put forth
effort and to persevere when things become more challenging. If a child's initial
efforts are met with a negative reaction, the likelihood that the child will
continue putting forth adequate effort diminishes. If left unchecked, a child's
overall level of functioning will likely be compromised. More importantly, the
child's sense of personal efficacy (e.g., self-esteem) and competence may suffer.

Clinical Manifestations
The symptoms and clinical manifestations of neurodevelopmental and executive
dysfunction differ with age. Preschool-age children might present with delayed
language development, including problems with articulation, vocabulary
development, word finding, and rhyming. They often experience early
challenges with learning colors, shapes, letters, and numbers; the alphabet; and
days of the week. Children with visual processing deficits may have difficulty
learning to draw and write and have problems with art activities. These children
might also have trouble discriminating between left and right. They might
encounter problems recognizing letters and words. Difficulty following
instructions, overactivity, and distractibility may be early symptoms of emerging
executive dysfunction. Difficulties with fine motor development (e.g., grasping
crayons/pencils, coloring, drawing) and social interaction may develop.
School-age children with neurodevelopmental and executive dysfunctions
can vary widely in clinical presentations. Their specific patterns of academic
performance and behavior represent final common pathways of
neurodevelopmental strengths and deficits interacting with environmental,
social, or cultural factors; temperament; educational experience; and intrinsic
resilience (Table 48.2 ). Children with language weaknesses might have
problems integrating and associating letters and sounds, decoding words,
deriving meaning, and being able to comprehend passages. Children with early
signs of a mathematics weakness might have difficulty with concepts of quantity
or with adding or subtracting without using concrete representation (e.g., their
fingers when calculating). Difficulty learning time concepts and confusion with
directions (right/left) might also be observed. Poor fine motor control and
coordination and poor planning can lead to writing problems. Attention and
behavioral regulation weaknesses observed earlier can continue, and together
with other executive functioning weaknesses (e.g., organization, initiation skills),
further complicate the child's ability to acquire and generalize new knowledge.
Children with weaknesses in WM may struggle to remember the steps necessary
to complete an activity or problem-solve. In social settings, these children often
have difficulty keeping up with more complex conversations.

Table 48.2

Neurodevelopmental Dysfunction Underlying Academic Disorders*

ACADEMIC DISORDER POTENTIAL UNDERLYING NEURODEVELOPMENTAL DYSFUNCTION
Reading Language
Phonologic processing
Verbal fluency
Syntactic and semantic skills
Memory
Working memory
Sequencing
Visual-spatial
Attention
Written expression, spelling Language
Phonologic processing
Syntactic and semantic skills
Graphomotor
Visual-spatial
Memory
Working memory
Sequencing
Attention
 Mathematics Visual-spatial
Memory
Working memory
Language
Sequencing
Graphomotor
Attention
* Isolated neurodevelopmental dysfunction can lead to a specific academic disorder, but more
often there is a combination of factors underlying weak academic performance. In addition to the
dysfunction in neurodevelopmental domains as listed in the table, the clinician must also consider
the possibility of limitations of intellectual and cognitive abilities or associated social and emotional
problems.

In middle school children the shift in cognitive, academic, and regulatory

demands can cause further difficulties for those with existing
neurodevelopmental and executive challenges. In reading and writing, middle
school children might present with transposition and sequencing errors; might
struggle with root words, prefixes, and suffixes; might have difficulty with
written expression; and might avoid reading and writing altogether. Challenges
completing word problems in math are common. Difficulty with recall of
information might also be experienced. Although observable in both lower and
more advanced grades, behavioral, emotional, and social difficulties tend to
become more salient in middle school children who experience cognitive or
academic problems.
High school students can present with deficient reading comprehension,
written expression, and slower processing efficiency. Difficulty in answering
open-ended questions, dealing with abstract information, and producing
executive control (e.g., self-monitoring, organization, planning, self-starting) is
often reported.

Academic Problems
Reading disorders (see Chapter 50 ) can stem from any number of
neurodevelopmental dysfunctions, as described earlier (see Table 48.2 ). Most
often, language and auditory processing weaknesses are present, as evidenced by
poor phonologic processing that results in deficiencies at the level of decoding
individual words and, consequently, a delay in automaticity (e.g., acquiring a
repertoire of words readers can identify instantly) that causes reading to be slow,
laborious, and frustrating. Deficits in other core neurodevelopmental domains
might also be present. Weak WM might make it difficult for a child to hold
sounds and symbols in mind while breaking down words into their component
sounds, or might cause reading comprehension problems. Some children
experience temporal-ordering weaknesses and struggle with reblending
phonemes into correct sequences. Memory dysfunction can cause problems with
recall and summarization of what was read. Some children with higher-order
cognitive deficiencies have trouble understanding what they read because they
lack a strong grasp of the concepts in a text. Although relatively rare as a cause
of reading difficulty, problems with visual-spatial functions (e.g., visual
perception) can cause children difficulty in recognizing letters. It is not unusual
for children with reading problems to avoid reading practice, and a delay in
reading proficiency becomes increasingly pronounced and difficult to remediate.
Spelling and writing impairments share many related underlying processing
deficits with reading, so it is not surprising that the 2 disorders often occur
simultaneously in school-age children (see Table 48.2 ). Core
neurodevelopmental weaknesses that underlie spelling difficulties include
phonologic and decoding difficulties, orthographic problems (coding letters and
words into memory), and morphologic deficits (use of suffixes, prefixes, and
root words). Problems in these areas can manifest as phonetically poor, yet
visually comparable approximations to the actual word (faght for fight ), spelling
that is phonetically correct but visually incorrect (fite for fight ), and inadequate
spelling patterns (played as plade). Children with memory disorders might
misspell words because of coding weaknesses. Others misspell because of poor
auditory WM that interferes with their ability to process letters. Sequencing
weaknesses often result in transposition errors when spelling.
Writing difficulties have been classified as disorder of written expression , or
dysgraphia (see Table 48.2 ). Although many of the same dysfunctions
described for reading and spelling can contribute to problems with writing,
written expression is the most complex of the language arts, requiring synthesis
of many neurodevelopmental functions (e.g., auditory, visual-spatial, memory,
executive; see Chapter 51.2 ). Weaknesses in these functions can result in written
output that is difficult to comprehend, disjointed, and poorly organized. The
child with WM challenges can lose track of what the child intended to write.
Attention deficits can make it difficult for a child to mobilize and sustain the
mental effort, pacing, and self-monitoring demands necessary for writing. In
many cases, writing is laborious because of an underlying graphomotor
dysfunction (e.g., fluency does not keep pace with ideation and language
production). Thoughts may also be forgotten or underdeveloped during writing
because the mechanical effort is so taxing.
 Weaknesses in mathematical ability, known as mathematics disorder or
dyscalculia , require early intervention because math involves the assimilation
of both procedural knowledge (e.g., calculations) and higher-order cognitive
processes (e.g., WM) (see Table 48.2 ). There are many reasons why children
experience failure in mathematics (see Chapter 51.1 ). It may be difficult for
some to grasp and apply math concepts effectively and systematically; good
mathematicians are able to use both verbal and perceptual conceptualization to
understand such concepts as fractions, percentages, equations, and proportion.
Children with language dysfunctions have difficulty in mathematics because
they have trouble understanding their teachers' verbal explanations of
quantitative concepts and operations and are likely to experience frustration in
solving word problems and in processing the vast network of technical
vocabulary in math. Mathematics also relies on visualization. Children who have
difficulty forming and recalling visual imagery may be at a disadvantage in
acquiring mathematical skills. They might experience problems writing numbers
correctly, placing value locations, and processing geometric shapes or fractions.
Children with executive dysfunction may be unable to focus on fine detail (e.g.,
operational signs), might take an impulsive approach to problem solving, engage
in little or no self-monitoring, forget components of the problem, or commit
careless errors. When a child's memory system is weak, the child might have
difficulty recalling appropriate procedures and automatizing mathematical facts
(e.g., multiplication tables). Moreover, children with mathematical disabilities
can have superimposed mathematics phobias ; anxiety over mathematics can be
especially debilitating.

Nonacademic Problems
The impulsivity and lack of effective self-monitoring of children with executive
dysfunction can lead to unacceptable actions that were unintentional. Children
struggling with neurodevelopmental dysfunction can experience excessive
performance anxiety, sadness, or clinical depression; declining self-esteem; and
chronic fatigue. Some children lose motivation. They tend to give up and exhibit
learned helplessness, a sense that they have no control over their destiny.
Therefore they feel no need to exert effort and develop future goals. These
children may be easily led toward dysfunctional interpersonal relationships,
detrimental behaviors (e.g., delinquency), and the development of mental health
disorders, such as mood disorders (see Chapter 39 ) or conduct disorder (Chapter
42 ).

Assessment and Diagnosis

Pediatricians have a critical role in identifying and treating the child with
neurodevelopmental or executive dysfunction (Fig. 48.1 ). They have knowledge
of the child's medical and family history and social-environmental circumstances
and have the benefit of longitudinal contact over the course of routine health
visits. Focused surveillance and screening will lead to early identification of
developmental-behavioral and preacademic difficulties and interventions to
facilitate optimal outcomes.
 FIG. 48.1 Primary care approach to neurodevelopmental and executive
dysfunction.

A family history of a parent who still struggles with reading or time

management, or an older sibling who has failed at school, should spur an
increased level of monitoring. Risk factors in the medical history, such as
extreme prematurity or chronic medical conditions, should likewise be flagged.
Children with low birthweight and those born prematurely who appear to have
been spared more serious neurologic problems might only manifest academic
problems later in their school career. Nonspecific physical complaints or
unexpected changes in behavior might be presenting symptoms. Warning signs
might be subtle or absent, and parents might have concerns about their child's
learning progress but may be reluctant to share these with the pediatrician unless
prompted, such as through completion of standardized developmental
screening questionnaires or direct questioning regarding possible concerns.
There should be a low threshold for initiating further school performance
screening and assessment if there are any “red flags.”
Review of school report cards can provide very useful information. In
addition to patterns of grades in the various academic skill areas, it is also
important to review ratings of classroom behavior and work habits. Group-
administered standardized tests provide further information, although
interpretation is required because poor scores could result from a learning
disorder, ADHD, anxiety, lack of motivation, or some combination. Conversely,
a discrepancy between above-average scores on standardized tests and
unsatisfactory classroom performance could signal motivation or adjustment
issues. Challenges related to homework can provide further insight regarding
executive, academic skill, and behavioral factors.
Underlying or associated medical problems should be ruled out. Any
suspicion of sensory difficulty should warrant referral for vision or hearing
testing . The influence of chronic medical problems or potential side effects of
medications should be considered. Sleep deprivation is increasingly being
recognized as a contributor to academic problems, especially in middle and high
school. Substance abuse must always be a consideration as well, especially in
the adolescent previously achieving well who has shown a rapid decline in
academic performance.
The physician should be alert for dysmorphic physical features, minor
congenital anomalies, or constellations of physical findings (e.g., cardiac and
palatal anomalies in velocardiofacial syndrome) and should perform a detailed
neurologic examination, including an assessment of fine and gross motor
coordination and any involuntary movements or soft neurologic signs. Special
investigations (e.g., genetic deletion-duplication microarray,
electroencephalogram, MRI) are not always indicated in the absence of specific
medical findings or a family history. Measures of brain function, such as
functional MRI, offer insight into possible areas of neurodevelopmental
dysfunction but remain primarily research tools.
Early signs of executive dysfunction can also be subtle and easily overlooked
or misinterpreted. Informal inquiry might include questions about how children
complete schoolwork or tasks, how organized or disorganized they are, how
much guidance they need, whether they think through problems or respond and
react too quickly, what circumstances or individuals affect their ability to employ
EFs, how easily they begin tasks and activities, and how well they plan, manage
belongings, and control their emotions.
Pediatricians who are interested in performing further assessment before
referral, or who are practicing in areas where psychological testing resources are
limited, can utilize standardized rating scales and inventories or brief,
individually administered tests to narrow potential diagnoses and guide next
steps in diagnosis and treatment. Such instruments, completed by the parents,
teachers, and the child (if old enough), can provide information about emotions
and behavior, patterns of academic performance, and traits associated with
specific neurodevelopmental dysfunctions (see Chapter 32 ). Screening
instruments such as the Pediatric Symptom Checklist and behavioral
questionnaires such as the Child Behavior Checklist (CBCL) and Behavior
Assessment System for Children, Second Edition (BASC-2) can aid in evaluation.
Instruments more specifically focused on academic disorders, such as the
Learning Disabilities Diagnostic Inventory, can be completed by the child's
teacher to reveal the extent to which skill patterns in a particular area (e.g.,
reading, writing) are consistent with those of individuals known to have a
learning disability.
Executive functions can be further assessed by instruments such as the
Behavior Rating Inventory of Executive Function, Second Edition (BRIEF2),
which provides a comprehensive measure of real-world behaviors that are
closely tied to executive functioning in children age 5-18 yr. An alternative
rating inventory of EF in children is the Comprehensive Executive Function
Inventory (CEFI). Tests that can be directly administered to gauge intellectual
functioning include the Kaufman Brief Intelligence Test, Second Edition (KBIT-
2) and Peabody Picture Vocabulary Test, Fourth Edi tion (PPVT 4; assessing
receptive vocabulary). A relatively brief test of academic skills is the Wide
Range Achievement Test 4 (WRAT4). It should be recognized that these are
midlevel tests that can provide descriptive estimates of function but are not
diagnostic.
Children who are struggling academically are entitled to evaluations in school.
Such assessments are guaranteed in the United States under Public Law 101-476,
the Individuals with Disabilities Education Act (IDEA) . One increasingly
common type of evaluation supported by IDEA is referred to as a response to
intervention (RtI) model (see Chapter 51.1 ). In this model, students who are
struggling with academic skills are initially provided research-based instruction.
If a child does not respond to this instruction, an individualized evaluation by a
multidisciplinary team is conducted. Children found to have attentional
dysfunction and other disorders might qualify for educational accommodations
in the regular classroom under Section 504 of the Rehabilitation Act of 1973
(504 plan ).
The pediatrician should advise and support parents regarding steps to request
evaluations by the school. Multidisciplinary evaluations are focused primarily on
determining whether a student meets the eligibility criteria for special education
services and to assist in developing an individualized educational plan (IEP)
for those eligible for these services. Independent evaluations can provide second
opinions outside the school setting. The multidisciplinary team should include a
psychologist and preferably an educational diagnostician who can undertake a
detailed analysis of academic skills and subskills to pinpoint where breakdowns
are occurring in the processes of reading, spelling, writing, and mathematics.
Other professionals should become involved, as needed, such as a speech-
language pathologist, occupational therapist, and social worker. A mental health
specialist can be valuable in identifying family-based issues or psychiatric
disorders that may be complicating or aggravating neurodevelopmental
dysfunctions.
In some cases, more in-depth examination of a child's neurocognitive status
is warranted. This is particularly true for children who present with
developmental or cognitive difficulties in the presence of a medical condition
(e.g., epilepsy, traumatic brain injury, childhood cancers/brain tumors, genetic
conditions). A neuropsychological evaluation involves comprehensive
assessment to understand brain functions across domains. Neuropsychological
data are often analyzed together with other tests, such as MRI, to look for
supporting evidence of any areas of difficulty (e.g., memory weaknesses
associated with temporal lobe anomalies). Neuropsychologists can also provide
more in-depth evaluation of EFs. Assessment of EFs is typically completed in an
examination setting using tools specifically designed to identify any weaknesses
in these functions. Although few tools are currently available to assess EF in
preschool-age children, the assessment of school-age children is better
established. Problems with EFs should be evaluated across measures and in
different settings, particularly within the context of the child's daily demands.

Treatment
In addition to addressing any underlying or associated medical problems, the
pediatrician can play an important role as a consultant and advocate in
overseeing and monitoring the implementation of a comprehensive
multidisciplinary management plan for children with neurodevelopmental
dysfunctions. Most children require several of the following forms of
intervention.

Demystification
Many children with neurodevelopmental dysfunctions have little or no
understanding of the nature or sources of their academic difficulties. Once an
appropriate descriptive assessment has been performed, it is important to explain
to the child the nature of the dysfunction while delineating the child's strengths.
This explanation should be provided in nontechnical language, communicating a
sense of optimism and a desire to be helpful and supportive.

Bypass Strategies (Accommodations)

Numerous techniques can enable a child to circumvent neurodevelopmental
dysfunctions. Such bypass strategies are ordinarily used in the regular classroom.
Examples of bypass strategies include using a calculator while solving
mathematical problems, writing essays with a word processor, presenting oral
instead of written reports, solving fewer mathematical problems, being seated
near the teacher to minimize distraction, presenting correctly solved
mathematical problems visually, and taking standardized tests untimed. These
bypass strategies do not cure neurodevelopmental dysfunctions, but they
minimize their academic and nonacademic effects and can provide a scaffold for
more successful academic achievement.

Treatment of Neurodevelopmental Dysfunctions

Interventions can be implemented at home and in school to strengthen the weak
links in academic skills. Reading specialists, mathematics tutors, and other
professionals can use diagnostic data to select techniques that use a student's
neurodevelopmental strengths to improve decoding skills, writing ability, or
mathematical computation skills. Remediation need not focus exclusively on
specific academic areas. Many students need assistance in acquiring study skills,
cognitive strategies, and productive organizational habits.
Early identification is critical so that appropriate instructional interventions
can be introduced to minimize the long-term effects of academic disorders. Any
interventions should be empirically supported (e.g., phonologically based
reading intervention has been shown to significantly improve reading skills in
school-age children). Remediation may take place in a resource room or learning
center at school and is usually limited to children who have met the educational
criteria for special education resource services described earlier.
Interventions that can be implemented at home could include drills to aid the
automatization of subskills, such as arithmetic facts or letter formations, or the
use of phonologically based reading programs.

Treatment of Executive Dysfunction

Interventions to strengthen EFs can be implemented throughout childhood but
are most effective if started at a young age. Preschool-age children first
experience EFs by way of the modeling, boundaries, and rules observed and
put in place by their parents/caregivers, and this modeled behavior must
gradually become “internalized” by the child. Early play has been shown to be
effective in promoting executive skills in younger children with games such as
peek-a-boo (WM); pat-a-cake (WM and IC); follow the leader, Simon says, and
“ring around the rosie” (self-control); imitation activities (attention and impulse
control); matching and sorting games (organization and attention); and
imaginary play (attention, WM, IC, self-monitoring, cognitive flexibility).
 In school-age children it is crucial to establish consistent cognitive and
behavioral routines that foster and maximize independent, goal-oriented
problem solving and performance through mechanisms that include modification
of the child's environment, modeling and guidance with the child, and positive
reinforcement strategies. Interventions should promote generalization (teaching
executive routines in the context of a problem, not as a separate skill) and should
move from the external to the internal (from “external support” with active and
directive modeling to an “internal process”). An intervention could proceed from
external modeling of multistep problem-solving routines and external guidance
in developing and implementing everyday routines, to practicing application and
use of routines in everyday situations, to a gradual fading of external support and
cueing of internal generation and use of executive skills. Such approaches should
make the child a part of intervention planning, should avoid labeling, reward
effort not outcomes, make interventions positive, and hold the child responsible
for his or her efforts. Studies have consistently shown that a combination of
medication and behavioral treatments are most effective, although evidence for
long term efficacy is lacking. It is important that any treatment plans aimed at
bolstering attention and executive functioning also include interventions that
address the specific deficits associated with any comorbid diagnoses.
In addition to behavioral approaches, computerized training programs have
been shown to strengthen WM skills in children using a computer game model.
Generalized and lasting improvements in WM have been reported. Also
evidencing positive outcomes are curriculum-based classroom programs , such
as the Tools of the Mind (Tools) and Promoting Alternative Thinking Strategies
(PATHS). Other promising approaches to EF intervention include aerobic
exercise, shown to improve EFs through prefrontal cortex stimulation. Martial
arts such as tae kwon do, which stresses discipline and self-regulation, has
demonstrated improvements that generalize in many aspects of EFs and attention
(e.g., sustained focus). Approaches that use mindfulness techniques are also
gaining prominence. Formal parenting interventions have also demonstrated
strong evidence for effectiveness. Four programs that have the most empirical
support are the Triple P, Parent-Child Interaction Therapy (PCIT), Incredible
Years, and New Forest Parenting Programme .
Table 48.3 outlines interventions to target the specific components of EF.
Although interventions may target each component separately, success will be
determined by how well treatments can be integrated across settings and
generalized to other areas of function. Whenever possible, working with more
than one EF simultaneously is encouraged as a means of scaffolding intervention
and building on previously mastered skills.

Table 48.3

Executive Function Categories: Presenting Symptoms, Suggested Dysfunction, and

Potential Interventions
SYMPTOM/PRESENTING SUSPECTED AREA
POSSIBLE “REAL WORLD” INTERVENTIONS
COMPLAINT OF DYSFUNCTION
Acts before thinking Disinhibition/impulsivity Increase structure in environment to set limits for
Interrupts inhibition problems.
Poor behavioral and/or Make behavior and work expectations clear and
emotional control explicit; review with child.
Post rules in view; point to them when child breaks
rule.
Teach response-delay techniques (e.g., counting to
10 before acting).
Cannot follow multistep Working memory Repeat instructions as needed.
instructions Keep instructions clear and concise.
Forgetful Provide concrete references.
Struggles starting Initiation Increase structure of tasks.
assignments/tasks Establish and rely on routine.
Lacks Break tasks into smaller, manageable steps.
initiative/motivation Place child with partner or group for modeling and
Has trouble developing cuing from peers.
ideas/strategies
Does not plan ahead Planning Practice with tasks with only a few steps first.
Uses trial-and-error Teach simple flow charting as a planning tool.
approach Practice with planning tasks (e.g., mazes).
Ask child to verbalize plan before beginning work.
Ask child to verbalize second plan if first does not
work.
Ask child to verbalize possible consequences of
actions before beginning.
Review incidents of poor planning/anticipation
with child.
Work/belongings is/are Organization Increase organization of classroom and activities to
“messy” serve as model, and help child grasp structure of
Random/haphazard new information.
problem solving Present framework of new information to be
Procrastinates/does not learned at the outset, and review again at the end of
complete tasks a lesson.
Begin with tasks with only few steps and increase
gradually.
Gets “stuck” Flexibility/shifting Increase routine to the day.
Trouble transitioning Make schedule clear and public.
Does not adapt to change Forewarn of any changes in schedule.
Give “2-minute warning” of time to change.
Make changes from one task to the next or one
topic to the next, clear and explicit.
Shifting may be a problem of inhibiting, so apply
 strategies for inhibition problems.

Developmental Therapy
Speech-language pathologists offer intervention for children with various forms
of language disability. Occupational therapists focus on sensorimotor skills,
including the motor skills of students with writing problems, and physical
therapists address gross motor incoordination.

Curriculum Modifications
Many children with neurodevelopmental dysfunctions require alterations in the
school curriculum to succeed, especially as they progress through secondary
school. Students with memory weaknesses might need to have their courses
selected for them so that they do not have an inordinate cumulative memory load
in any single semester. The timing of foreign language learning, the selection of
a mathematics curriculum, and the choice of science courses are critical issues
for many of these struggling adolescents.

Strengthening of Strengths
Affected children need to have their affinities, potentials, and talents identified
clearly and exploited widely. It is as important to augment strengths as it is to
attempt to remedy deficiencies. Athletic skills, artistic inclinations, creative
talents, and mechanical abilities are among the potential assets of certain
students who are underachieving academically. Parents and school personnel
need to create opportunities for such students to build on these assets and to
achieve respect and praise for their efforts. These well-developed personal assets
can ultimately have implications for the transition into young adulthood,
including career or college selection.

Individual and Family Counseling

When academic difficulties are complicated by family problems or identifiable
psychiatric disorders, psychotherapy may be indicated. Mental health
professionals may offer long-term or short-term therapy. Such intervention may
involve the child alone or the entire family. Cognitive-behavioral therapy is
especially effective for mood and anxiety disorders. It is essential that the
therapist have a firm understanding of the nature of a child's neurodevelopmental
dysfunctions.

Nonstandard Therapies
A variety of treatment methods for neurodevelopmental dysfunctions have been
proposed that currently have little to no known scientific evidence of efficacy.
This list includes dietary interventions (vitamins, elimination of food additives
or potential allergens), neuromotor programs or medications to address
vestibular dysfunction, eye exercises, filters, tinted lenses, and various
technologic devices. Parents should be cautioned against expending the
excessive amounts of time and financial resources usually demanded by these
remedies. In many cases, it is difficult to distinguish the nonspecific beneficial
effects of increased support and attention paid to the child from the supposed
target effects of the intervention.

Medication
Psychopharmacologic agents may be helpful in lessening the toll of some
neurodevelopmental dysfunctions. Most often, stimulants are used in the
treatment of children with attention deficits. Although most children with
attention deficits have other associated dysfunctions, such as language disorders,
memory problems, motor weaknesses, or social skill deficits, medications such
as methylphenidate, dextroamphetamine, lisdexamfetamine, and mixed
amphetamine salts, as well as nonstimulants such as α2 -adrenergic agonists
and atomoxetine , can be important adjuncts to treatment by helping some
children focus more selectively and control their impulsivity. When depression
or excessive anxiety is a significant component of the clinical picture,
antidepressants or anxiolytics may be helpful. Other drugs may improve
behavioral control (see Chapter 33 ). Children receiving medication need regular
follow-up visits that include a history to check for side effects, a review of
current behavioral checklists, a complete physical examination, and appropriate
modifications of the medication dose. Periodic trials off medication are
recommended to establish whether the medication is still necessary.
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CHAPTER 49

Attention-Deficit/Hyperactivity
Disorder
David K. Urion

Attention-deficit/hyperactivity disorder (ADHD) is the most common

neurobehavioral disorder of childhood, among the most prevalent chronic health
conditions affecting school-aged children, and one of the most extensively
studied neurodevelopmental disorders of childhood. ADHD is characterized by
inattention, including increased distractibility and difficulty sustaining attention;
poor impulse control and decreased self-inhibitory capacity; and motor
overactivity and motor restlessness (Table 49.1 and Fig. 49.1 ). Definitions vary
in different countries (Table 49.2 ). Affected children usually experience
academic underachievement, problems with interpersonal relationships with
family members and peers, and low self-esteem. ADHD often co-occurs with
other emotional, behavioral, language, and learning disorders (Table 49.3 ).
Evidence also suggests that for many people, the disorder continues with varying
manifestations across the life cycle, leading to significant under- and
unemployment, social dysfunction and increased risk of antisocial behaviors
(e.g., substance abuse), difficulty maintaining relationships, encounters with the
law, death from suicide, and, if untreated, accidents (Figs. 49.2 and 49.3 ).
Table 49.1
DSM-5 Diagnostic Criteria for Attention-
Deficit/Hyperactivity Disorder (ADHD)

A. A persistent pattern of inattention and/or hyperactivity/impulsivity that

interferes with functioning or development, as characterized by (1) and/or
(2):
1. Inattention: Six (or more) of the following symptoms of
inattention have persisted for ≥6 mo to a degree that is
inconsistent with development level and that negatively impacts
directly on social and academic/occupational activities:
a. Often fails to give close attention to details or makes
careless mistakes in schoolwork, at work, or during other
activities (e.g., overlooks or misses details, work is
inaccurate).
b. Often has difficulty sustaining attention in tasks or play
activities.
c. Often does not seem to listen when spoken to directly.
d. Often does not follow through on instructions and fails
to finish schoolwork, chores, or duties in the workplace
(not due to oppositional behavior or failure to understand
instructions).
e. Often has difficulty organizing tasks and activities.
f. Often avoids, dislikes, or is reluctant to engage in tasks
that require sustained mental effort (e.g., schoolwork,
homework).
g. Often loses things necessary for tasks or activities (e.g.,
toys, school assignments, pencils, books, tools).
h. Is often easily distracted by extraneous stimuli.
i. Is often forgetful in daily activities.
2. Hyperactivity/impulsivity: Six (or more) of the following
symptoms of inattention have persisted for ≥6 mo to a degree that
is inconsistent with development level and that negatively
impacts directly on social and academic/occupational activities.
a. Often fidgets with hands or feet or squirms in seat.
b. Often leaves seat in classroom or in other situations in
which remaining seated is expected.
c. Often runs about or climbs excessively in situations in
which it is inappropriate (in adolescents or adults, may
be limited to subjective feelings of restlessness).
d. Often has difficulty playing or engaging in leisure
activities quietly.
e. Is often “on the go” or often acts as if “driven by a
motor.”
 f. Often talks excessively.
Impulsivity.
g. Often blurts out answers before questions have been
completed.
h. Often has difficulty awaiting turn.
i. Often interrupts or intrudes on others (e.g., butts into
conversations or games).
B. Several inattentive or hyperactive/impulsive symptoms were present
before 12 yr of age.
C. Several inattentive or hyperactive/impulsive symptoms are present in 2 or
more settings (e.g., at school [or work] or at home) and is documented
independently.
D. There is clear evidence of clinically significant impairment in social,
academic, or occupational functioning.
E. Symptoms do not occur exclusively during the course of schizophrenia, or
another psychotic disorder, and are not better accounted for by another
mental disorder (e.g., mood disorder, anxiety disorder, dissociative
disorder, personality disorder, substance intoxication or withdrawal).

Code Based on Type

314.01 Attention-deficit/hyperactivity disorder, combined presentation: if

both Criteria A1 and A2 are met for the past 6 mo.
314.00 Attention-deficit/hyperactivity disorder, predominantly inattentive
presentation: if Criterion A1 is met but Criterion A2 is not met for the
past 6 mo.
314.01 Attention-deficit/hyperactivity disorder, predominantly hyperactive-
impulsive presentation: if Criterion A2 is met but Criterion A1 is not met
for the past 6 mo.
Specify if:
Mild: Few, if any, symptoms in excess of those required to make
the diagnosis are present, and if the symptoms result in no more
than minor impairments in social and occupational functioning.
Moderate: Symptoms or functional impairment between “mild”
and “severe” are present.
Severe: Many symptoms in excess of those required to make the
 diagnosis, or several symptoms that are particularly severe, are
present, or the symptoms result in marked impairment in social
or occupational functioning.

From the Diagnostic and Statistical Manual of Mental Disorders, Fourth

Edition, Text Revision, Washington, DC, 2000, and Fifth Edition, (Copyright
2013). American Psychiatric Association.

FIG. 49.1 How to assess children for attention-deficit/hyperactivity

disorder. (From Verkuijl N, Perkins M, Fazel M: Childhood attention-
deficit/hyperactivity disorder, BMJ 350:h2168, 2015, Fig 2, p 146.)

Table 49.2
Differences Between U.S. and European Criteria for ADHD
or HKD

DSM-5 ADHD ICD-10 HKD

SYMPTOMS
Either or both of the following: All of the following:
At least 6 of 9 inattentive symptoms At least 6 of 8 inattentive symptoms
At least 6 of 9 hyperactive or impulsive symptoms At least 3 of 5 hyperactive symptoms
At least 1 of 4 impulsive symptoms
 PERVASIVENESS
Some impairment from symptoms is present in >1 setting Criteria are met for >1 setting
ADHD, Attention-deficit/hyperactivity disorder; HKD, hyperkinetic disorder; DSM-5, Diagnostic and
Statistical Manual of Mental Disorders, Fifth Edition ; ICD-10, International Classification of
Diseases, Tenth Edition .
From Biederman J, Faraone S: Attention-deficit hyperactivity disorder, Lancet 366:237–248, 2005.

Table 49.3
Differential Diagnosis of Attention-
Deficit/Hyperactivity Disorder (ADHD)
Psychosocial Factors

Response to physical or sexual abuse

Response to inappropriate parenting practices
Response to parental psychopathology
Response to acculturation
Response to inappropriate classroom setting

Diagnoses Associated With ADHD Behaviors

Fragile X syndrome
Fetal alcohol syndrome
Pervasive developmental disorders
Obsessive-compulsive disorder
Gilles de la Tourette syndrome
Attachment disorder with mixed emotions and conduct

Medical and Neurologic Conditions

Thyroid disorders (including general resistance to thyroid hormone)

Heavy metal poisoning (including lead)
Adverse effects of medications
Effects of abused substances
Sensory deficits (hearing and vision)
Auditory and visual processing disorders
Neurodegenerative disorder, especially leukodystrophies
 Posttraumatic head injury
Postencephalitic disorder

Note: Coexisting conditions with possible ADHD presentation include

oppositional defiant disorder, anxiety disorders, conduct disorder, depressive
disorders, learning disorders, and language disorders. Presence of one or more
of the symptoms of these disorders can fall within the spectrum of normal
behavior, whereas a range of these symptoms may be problematic but fall short
of meeting the full criteria for the disorder.

From Reiff MI, Stein MT: Attention-deficit/hyperactivity disorder evaluation

and diagnosis: a practical approach in office practice, Pediatr Clin North Am
50:1019–1048, 2003. Adapted from Reiff MI: Attention-deficit/hyperactivity
disorders. In Bergman AB, editor: 20 Common problems in pediatrics, New
York, 2001, McGraw-Hill, p 273.

FIG. 49.2 Possible developmental impacts of attention-deficit/hyperactivity

disorder. (From Verkuijl N, Perkins M, Fazel M: Childhood attention-
deficit/hyperactivity disorder, BMJ 350:h2168, 2015, Fig 1, p 145.)
 FIG. 49.3 Pathways to premature death in persons with attention-
deficit/hyperactivity disorder (ADHD). (From Faraone SV: Attention deficit
hyperactivity disorder and premature death, Lancet 385:2132–2133,
2015.)

Etiology
No single factor determines the expression of ADHD; ADHD may be a final
common pathway for a variety of complex brain developmental processes.
Mothers of children with ADHD are more likely to experience birth
complications, such as toxemia, lengthy labor, and complicated delivery.
Maternal drug use has also been identified as a risk factor in the development of
ADHD. Maternal smoking, alcohol use during pregnancy, and prenatal or
postnatal exposure to lead are frequently linked to the attentional difficulties
associated with development of ADHD, but less clearly to hyperactivity. Food
coloring and preservatives have inconsistently been associated with increased
hyperactivity in children with ADHD.
There is a strong genetic component to ADHD. Genetic studies have primarily
implicated 2 candidate genes, the dopamine transporter gene (DAT1) and a
particular form of the dopamine 4 receptor gene (DRD4), in the development of
ADHD. Additional genes that might contribute to ADHD include DOCK2,
associated with a pericentric inversion 46N inv(3)(p14:q21) involved in cytokine
regulation; a sodium-hydrogen exchange gene; and DRD5, SLC6A3, DBH,
SNAP25, SLC6A4, and HTR1B.
Structural and functional abnormalities of the brain have been identified in
children with ADHD. These include dysregulation of the frontal subcortical
circuits, small cortical volumes in this region, widespread small-volume
reduction throughout the brain, and abnormalities of the cerebellum, particularly
midline/vermian elements (see Pathogenesis ). Brain injury also increases the
risk of ADHD. For example, 20% of children with severe traumatic brain injury
are reported to have subsequent onset of substantial symptoms of impulsivity
and inattention. However, ADHD may also increase the risk of traumatic brain
injury.
Psychosocial family stressors can also contribute to or exacerbate the
symptoms of ADHD, including poverty, exposure to violence, and
undernutrition or malnutrition.

Epidemiology
Studies of the prevalence of ADHD worldwide have generally reported that 5–
10% of school-age children are affected, although rates vary considerably by
country, perhaps in part because of differing sampling and testing techniques.
Rates may be higher if symptoms (inattention, impulsivity, hyperactivity) are
considered in the absence of functional impairment. The prevalence rate in
adolescent samples is 2–6%. Approximately 2% of adults meet criteria for
ADHD. ADHD is often underdiagnosed in children and adolescents. Youth with
ADHD are often undertreated with respect to what is known about the needed
and appropriate doses of medications. Many children with ADHD also present
with comorbid neuropsychiatric diagnoses, including oppositional defiant
disorder, conduct disorder, learning disabilities, and anxiety disorders. The
incidence of ADHD appears increased in children with neurologic disorders such
as the epilepsies, neurofibromatosis, and tuberous sclerosis (see Table 49.3 ).

Pathogenesis
Brain MRI studies in children with ADHD indicate a reduction or even loss of
the normal hemispheric asymmetry in the brain, as well as smaller brain volumes
of specific structures, such as the prefrontal cortex and basal ganglia. Children
with ADHD have approximately a 5–10% reduction in the volume of these brain
structures. MRI findings suggest low blood flow to the striatum. Functional MRI
data suggest deficits in dispersed functional networks for selective and sustained
attention in ADHD that include the striatum, prefrontal regions, parietal lobe,
and temporal lobe. The prefrontal cortex and basal ganglia are rich in dopamine
receptors. This knowledge, plus data about the dopaminergic mechanisms of
action of medication treatment for ADHD, has led to the dopamine hypothesis,
which postulates that disturbances in the dopamine system may be related to the
onset of ADHD. Fluorodopa positron emission tomography (PET) scans also
support the dopamine hypothesis through the identification of low levels of
dopamine activity in adults with ADHD.

Clinical Manifestations
Development of the Diagnostic and Statistical Manual of Mental Disorders,
Fifth Edition (DSM-5) criteria leading to the diagnosis of ADHD has occurred
mainly in field trials with children 5-12 yr of age (see Table 49.1 and Fig. 49.1 ).
The DSM-5 notably expanded the accepted age of onset for symptoms of
ADHD, and studies utilizing these broader criteria demonstrate a good
correlation with data from DSM-IV criteria–based studies. The current DSM-5
criteria state that the behavior must be developmentally inappropriate
(substantially different from that of other children of the same age and
developmental level), must begin before age 12 yr, must be present for at least 6
mo, must be present in 2 or more settings and reported as such by independent
observers, and must not be secondary to another disorder. DSM-5 identifies three
presentations of ADHD. The inattentive presentation is more common in
females and is associated with relatively high rates of internalizing symptoms
(anxiety and low mood). The other two presentations, hyperactive-impulsive
and combined , are more often diagnosed in males (see Fig. 49.1 ).
Clinical manifestations of ADHD may change with age (see Fig. 49.2 ). The
symptoms may vary from motor restlessness and aggressive and disruptive
behavior, which are common in preschool children, to disorganized, distractible,
and inattentive symptoms, which are more typical in older adolescents and
adults. ADHD is often difficult to diagnose in preschoolers because
distractibility and inattention are often considered developmental norms during
this period.

Diagnosis and Differential Diagnosis

A diagnosis of ADHD is made primarily in clinical settings after a thorough
evaluation, including a careful history and clinical interview to rule in or to
identify other causes or contributing factors; completion of behavior rating
scales by different observers from at least 2 settings (e.g., teacher and parent); a
physical examination; and any necessary or indicated laboratory tests that arise
from conditions suspected based on history and/or physical examination. It is
important to systematically gather and evaluate information from a variety of
sources, including the child, parents, teachers, physicians, and when appropriate,
other caretakers, over the course of both diagnosis and subsequent management.

Clinical Interview and History

The clinical interview allows a comprehensive understanding of whether the
symptoms meet the diagnostic criteria for ADHD. During the interview, the
clinician should gather information pertaining to the history of the presenting
problems, the child's overall health and development, and the social and family
history. The interview should emphasize factors that might affect the
development or integrity of the central nervous system or reveal chronic illness,
sensory impairments, sleep disorders, or medication use that might affect the
child's functioning. Disruptive social factors, such as family discord, situational
stress, and abuse or neglect, can result in hyperactive or anxious behaviors. A
family history of first-degree relatives with ADHD, mood or anxiety disorders,
learning disability, antisocial disorder, or alcohol or substance abuse might
indicate an increased risk of ADHD and comorbid conditions.

Behavior Rating Scales

Behavior rating scales are useful in establishing the magnitude and
pervasiveness of the symptoms, but are not sufficient alone to make a diagnosis
of ADHD. A variety of well-established behavior rating scales have obtained
good results in discriminating between children with ADHD and controls. These
measures include, but are not limited to, the Vanderbilt ADHD Diagnostic
Rating Scale, the Conner Rating Scales (parent and teacher), ADHD Rating
Scale 5, the Swanson, Nolan, and Pelham Checklist (SNAP), and the ADD-H:
Comprehensive Teacher Rating Scale (ACTeRS). Other broad-band checklists,
such as the Achenbach Child Behavior Checklist (CBCL) or Behavioral
Assessment Scale for Children (BASC), are useful, particularly when the child
may be experiencing coexisting problems in other areas (anxiety, depression,
conduct problems). Some, such as the BASC, include a validation scale to help
determine the reliability of a given observer's assessment of the child.

Physical Examination and Laboratory Findings

No laboratory tests are available to identify ADHD in children. The presence of
hypertension, ataxia, or symptoms of a sleep or thyroid disorder should prompt
further neurologic or endocrine diagnostic evaluation. Impaired fine motor
movement and poor coordination and other subtle neurologic motor signs
(difficulties with finger tapping, alternating movements, finger-to-nose,
skipping, tracing a maze, cutting paper) are common but not sufficiently specific
to contribute to a diagnosis of ADHD. The clinician should also identify any
possible vision or hearing problems. The clinician should consider testing for
elevated lead levels in children who present with some or all of the diagnostic
criteria, if these children are exposed to environmental factors that might put
them at risk (substandard housing, old paint, proximity to highway with
deposition of lead in topsoil from automobile exhaust years ago). Behavior in the
structured laboratory setting might not reflect the child's typical behavior in the
home or school environment. Thus, computerized attentional tasks and
electroencephalographic assessments are not needed to make the diagnosis, and
compared to the clinical gold standard, these are subject to false-positive and
false-negative errors. Similarly, observed behavior in a physician's office is not
sufficient to confirm or rule-out the diagnosis of ADHD.

Differential Diagnosis
Chronic illnesses, such as migraine headaches, absence seizures,
asthma/allergies, hematologic disorders, diabetes, and childhood cancer, affect
up to 20% of U.S. children and can impair children's attention and school
performance, because of either the disease itself or the medications used to treat
or control the underlying illness (medications for asthma, corticosteroids,
anticonvulsants, antihistamines) (see Table 49.3 ). In older children and
adolescents, substance abuse can result in declining school performance and
inattentive behavior (see Chapter 140 ).
Sleep disorders , including those secondary to chronic upper airway
obstruction from enlarged tonsils and adenoids, often result in behavioral and
emotional symptoms that can resemble or exacerbate ADHD (see Chapter 31 ).
Periodic leg movements of sleep/restless leg syndrome has been associated with
attentional symptoms, and inquiry regarding this should be made during the
history. Behavioral and emotional disorders can cause disrupted sleep patterns as
well.
Depression and anxiety disorders can cause many of the same symptoms as
ADHD (inattention, restlessness, inability to focus and concentrate on work,
poor organization, forgetfulness) but can also be comorbid conditions (see
Chapters 38 and 39 ). Obsessive-compulsive disorder can mimic ADHD,
particularly when recurrent and persistent thoughts, impulses, or images are
intrusive and interfere with normal daily activities. Adjustment disorders
secondary to major life stresses (death of a close family member, parents'
divorce, family violence, parents' substance abuse, a move, shared social trauma
such as bombings or other attacks) or parent–child relationship disorders
involving conflicts over discipline, overt child abuse and/or neglect, or
overprotection can result in symptoms similar to those of ADHD.
Although ADHD is believed to result from primary impairment of attention,
impulse control, and motor activity, there is a high prevalence of comorbidity
with other neuropsychiatric disorders (see Table 49.3 ). Of children with ADHD,
15–25% have learning disabilities, 30–35% have developmental language
disorders, 15–20% have diagnosed mood disorders, and 20–25% have coexisting
anxiety disorders. Children with ADHD can also have concurrent diagnoses of
sleep disorders, memory impairment, and decreased motor skills.

Treatment
Psychosocial Treatments
Once the diagnosis of ADHD has been established, the parents and child should
be educated with regard to the ways ADHD can affect learning, behavior, self-
esteem, social skills, and family function. The clinician should set goals for the
family to improve the child's interpersonal relationships, develop study skills,
and decrease disruptive behaviors. Parent support groups with appropriate
professional consultation to such groups can be very helpful.

Behaviorally Oriented Treatments

Treatments geared toward behavioral management often occur in the time frame
of 8-12 sessions. The goal of such treatment is for the clinician to identify
targeted behaviors that cause impairment in the child's life (disruptive behavior,
difficulty in completing homework, failure to obey home or school rules) and for
the child to work on progressively improving his or her skill in these areas. The
clinician should guide the parents and teachers in setting appropriate
expectations, consistently implementing rewards to encourage desired behaviors
and consequences to discourage undesired behaviors. In short-term comparison
trials, stimulants have been more effective than behavioral treatments used alone
in improving core ADHD symptoms for most children. Behavioral interventions
are modestly successful at improving core ADHD symptoms and are considered
the first-line treatment in preschool-age children with ADHD. In addition,
behavioral treatment may be particularly useful for children with comorbid
anxiety, complex comorbidities, family stressors, and when combined with
medication.

Medications
The most widely used medications for the treatment of ADHD are the
presynaptic dopaminergic agonists, commonly called psychostimulant
medications, including methylphenidate, dexmethylphenidate, amphetamine, and
various amphetamine and dextroamphetamine preparations. Longer-acting,
once-daily forms of each of the major types of stimulant medications are
available and facilitate compliance with treatment and coverage over a longer
period (see Table 49.3 ). When starting a stimulant, the clinician can select either
a methylphenidate-based or an amphetamine-based compound. If a full range of
methylphenidate dosages is used, approximately 25% of patients have an
optimal response on a low dose (<0.5 mg/kg/day for methylphenidate, <0.25
mg/kg/day for amphetamines), 25% on a medium dose (0.5-1.0 mg/kg/day for
methylphenidate, 0.25-0.5 mg/kg/day for amphetamines), and 25% on a high
dose (1.0-1.5 mg/day for methylphenidate, 0.5-0.75 mg/kg/day for
amphetamine); another 25% will be unresponsive or will have side effects,
making that drug particularly unpalatable for the family (See Table 33.2 for more
information on dosing).
Over the first 4 wk of treatment, the physician should increase the medication
dose as tolerated (keeping side effects minimal to absent) to achieve maximum
benefit. If this strategy does not yield satisfactory results, or if side effects
prevent further dose adjustment in the presence of persisting symptoms, the
clinician should use an alternative class of stimulants that was not used
previously. If a methylphenidate compound is unsuccessful, the clinician should
switch to an amphetamine product. If satisfactory treatment results are not
obtained with the 2nd stimulant, clinicians may choose to prescribe atomoxetine,
a noradrenergic reuptake inhibitor that has been approved by the U.S. Food and
Drug Administration (FDA) for the treatment of ADHD in children, adolescents,
and adults. Atomoxetine should be initiated at a dose of 0.3 mg/kg/day and
titrated over 1-3 wk to a maximum total daily dosage of 1.2-1.4 mg/kg/day. The
dose should be divided into twice-daily portions. Once-daily dosing appears to
be associated with a high incidence of treatment failure. Long-acting guanfacine
and clonidine are also FDA approved for the treatment of ADHD (see Chapter
33 ). These medications can also treat motor and vocal tics and so may be a
reasonable choice in a child with a comorbid tic disorder. Drugs to treat ADHD
do not increase the incidence of tics in children predisposed to a tic disorder. In
the past, tricyclic antidepressants have been used to treat ADHD, but TCAs are
rarely used now because of the risk of sudden death, particularly if an overdose
is taken.
The clinician should consider careful monitoring of medication a necessary
component of treatment in children with ADHD. When physicians prescribe
medications for the treatment of ADHD, they tend to use lower-than-optimal
doses. Optimal treatment usually requires somewhat higher doses than tend to be
found in routine practice settings. All-day preparations are also useful to
maximize positive effects and minimize side effects, and regular medication
follow-up visits should be offered (≥4 times/yr) as opposed to the twice-yearly
medication visits often used in standard community care settings.
Medication alone may not be sufficient to treat ADHD in children,
particularly when children have multiple psychiatric disorders or a stressed home
environment. When children do not respond to medication, it may be appropriate
to refer them to a mental health specialist. Consultation with a child psychiatrist,
developmental-behavioral pediatrician, or psychologist can also be beneficial to
determine the next steps for treatment, including adding other components and
supports to the overall treatment program. Evidence suggests that children who
receive careful medication management, accompanied by frequent treatment
follow-up, all within the context of an educative, supportive relationship with the
primary care provider, are likely to experience behavioral gains.
Stimulant drugs used to treat ADHD may be associated with an increased risk
of adverse cardiovascular events, including sudden cardiac death, myocardial
infarction, and stroke, in young adults and rarely in children. In some of the
reported cases, the patient had an underlying disorder, such as hypertrophic
obstructive cardiomyopathy, which is made worse by sympathomimetic agents.
These events are rare but nonetheless warrant consideration before initiating
treatment and during monitoring of therapy with stimulants. Children with a
positive personal or family history of cardiomyopathy, arrhythmias, or syncope
require an electrocardiogram and possible cardiology consultation before a
stimulant is prescribed (Fig. 49.4 ).

FIG. 49.4 Cardiac evaluation of children and adolescents with ADHD

receiving or being considered for stimulant medications. (From Perrin JM,
Friedman RA, Knilans TK: Cardiovascular monitoring and stimulant drugs
for attention-deficit/hyperactivity disorder, Pediatrics 122:451–453, 2008.)

Prognosis
A childhood diagnosis of ADHD often leads to persistent ADHD throughout the
life span. From 60–80% of children with ADHD continue to experience
symptoms in adolescence, and up to 40–60% of adolescents exhibit ADHD
symptoms into adulthood. In children with ADHD, a reduction in hyperactive
behavior often occurs with age. Other symptoms associated with ADHD can
become more prominent with age, such as inattention, impulsivity, and
disorganization, and these exact a heavy toll on young adult functioning. Risk
factors in children with untreated ADHD as they become adults include
engaging in risk-taking behaviors (sexual activity, delinquent behaviors,
substance use), educational underachievement or employment difficulties, and
relationship difficulties. With proper treatment, the risks associated with ADHD,
including injuries, can be significantly reduced. Consistent treatment with
medication and adjuvant therapies appears to lower the risk of adverse outcomes,
such as substance abuse.

Prevention
Parent training can lead to significant improvements in preschool children with
ADHD symptoms, and parent training for preschool youth with ADHD can
reduce oppositional behavior. To the extent that parents, teachers, physicians,
and policymakers support efforts for earlier detection, diagnosis, and treatment,
prevention of long-term adverse effects of ADHD on affected children's lives
should be reconsidered within the lens of prevention. Given the effective
treatments for ADHD now available, and the well-documented evidence about
the long-term effects of untreated or ineffectively treated ADHD on children and
youth, prevention of these consequences should be within the grasp of
physicians and the children and families with ADHD for whom we are
responsible.

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CHAPTER 50

Dyslexia
Sally E. Shaywitz, Bennett A. Shaywitz

The most current definition of dyslexia is now codified in U.S. Federal law (First
Step Act of 2018, PL: 115–391): “The term dyslexia means an unexpected
difficulty in reading for an individual who has the intelligence to be a much
better reader, most commonly caused by a difficulty in the phonological
processing (the appreciation of the individual sounds of spoken language), which
affects the ability of an individual to speak, read, and spell.” In typical readers,
development of reading and intelligence quotient (IQ) are dynamically linked
over time. In dyslexic readers, however, a developmental uncoupling occurs
between reading and IQ (Fig. 50.1 ), such that reading achievement is
significantly below what would be expected given the individual's IQ. The
discrepancy between reading achievement and IQ provides the long-sought
empirical evidence for the seeming paradox between cognition and reading in
individuals with developmental dyslexia, and this discrepancy is now recognized
in the Federal definition as unexpected difficulty in reading.
 FIG. 50.1 Uncoupling of reading and IQ over time: empirical evidence for a definition
of dyslexia. Left , In typical readers, reading and IQ development are dynamically linked
over time. Right, In contrast, reading and IQ development are dissociated in dyslexic
readers, and one does not influence the other. (Data adapted from Ferrer E, Shaywitz
BA, Holahan JM, et al: Uncoupling of reading and IQ over time: empirical evidence for a
definition of dyslexia, Psychol Sci 21(1):93–101, 2010.)

Etiology
Dyslexia is familial, occurring in 50% of children who have a parent with
dyslexia, in 50% of the siblings of dyslexic persons, and in 50% of the parents of
dyslexic persons. Such observations have naturally led to a search for genes
responsible for dyslexia, and at one point there was hope that heritability would
be related to a small number of genes. Genome-wide association studies
(GWAS), however, have demonstrated that a large number of genes are involved,
each producing a small effect. Advances in genetics have confirmed what the
GWAS suggested, that complex traits such as reading are the work of thousands
of genetic variants, working in concert (see Chapter 99 ). Thus, pediatricians
should be wary of recommending any genetic test to their patients that purports
to diagnose dyslexia in infancy or before language and reading have even
emerged. It is unlikely that a single gene or even a few genes will reliably
identify people with dyslexia. Rather, dyslexia is best explained by multiple
genes , each contributing a small amount toward the expression of dyslexia.
Epidemiology
Dyslexia is the most common and most comprehensively studied of the learning
disabilities, affecting 80% of children identified as having a learning disability.
Dyslexia may be the most common neurobehavioral disorder affecting children,
with prevalence rates ranging from 20% in unselected population-based samples
to much lower rates in school-identified samples. The low prevalence rate in
school-identified samples may reflect the reluctance of schools to identify
dyslexia. Dyslexia occurs with equal frequency in boys and girls in survey
samples in which all children are assessed. Despite such well-documented
findings, schools continue to identify more boys than girls, probably reflecting
the more rambunctious behavior of boys who come to the teacher's attention
because of misbehavior, while girls with reading difficulty, who are less likely to
be misbehaving, are also less likely to be identified by the schools. Dyslexia fits
a dimensional model in which reading ability and disability occur along a
continuum, with dyslexia representing the lower tail of a normal distribution of
reading ability.

Pathogenesis
Evidence from a number of lines of investigation indicates that dyslexia reflects
deficits within the language system, and more specifically, within the
phonologic component of the language system engaged in processing the
sounds of speech. Individuals with dyslexia have difficulty developing an
awareness that spoken words can be segmented into smaller elemental units of
sound (phonemes), an essential ability given that reading requires that the reader
map or link printed symbols to sound. Increasing evidence indicates that
disruption of attentional mechanisms may also play an important role in reading
difficulties.
Functional brain imaging in both children and adults with dyslexia
demonstrates an inefficient functioning of left hemisphere posterior brain
systems, a pattern referred to as the neural signature of dyslexia (Fig. 50.2 ).
Although functional magnetic resonance imaging (fMRI) consistently
demonstrates differences between groups of dyslexic compared to typical
readers, brain imaging is not able to differentiate an individual case of a dyslexic
reader from a typical reader and thus is not useful in diagnosing dyslexia.
 FIG. 50.2 A neural signature for dyslexia. The left side of the figure shows a schematic
of left hemisphere brain systems in in typical (nonimpaired) readers. The 3 systems for
reading are an anterior system in the region of the inferior frontal gyrus (Broca's area),
serving articulation and word analysis, and 2 posterior systems, 1 in the
occipitotemporal region serving word analysis, and a 2nd in the occipitotemporal
region (the word-form area) serving the rapid, automatic, fluent identification of words.
In dyslexic readers (right side of figure), the 2 posterior systems are functioning
inefficiently and appear underactivated. This pattern of underactivation in left posterior
reading systems is referred to as the neural signature for dyslexia. (Adapted from
Shaywitz S: Overcoming dyslexia: a new and complete science-based program for
reading problems at any level. New York, 2003, Alfred A. Knopf. Copyright 2003 by S.
Shaywitz. Adapted with permission.)

Clinical Manifestations
Reflecting the underlying phonologic weakness, children and adults with
dyslexia manifest problems in both spoken and written language. Spoken
language difficulties are typically manifest by mispronunciations, lack of
glibness, speech that lacks fluency with many pauses or hesitations and “ums,”
word-finding difficulties with the need for time to summon an oral response, and
the inability to come up with a verbal response quickly when questioned; these
reflect sound-based, not semantic or knowledge-based, difficulties.
Struggles in decoding and word recognition can vary according to age and
developmental level. The cardinal signs of dyslexia observed in school-age
children and adults are a labored, effortful approach to reading involving
decoding, word recognition, and text reading. Listening comprehension is
typically robust. Older children improve reading accuracy over time, but without
commensurate gains in reading fluency; they remain slow readers. Difficulties in
spelling typically reflect the phonologically based difficulties observed in oral
reading. Handwriting is often affected as well.
History often reveals early subtle language difficulties in dyslexic children.
During the preschool and kindergarten years, at-risk children display difficulties
playing rhyming games and learning the names for letters and numbers.
Kindergarten assessments of these language skills can help identify children at
risk for dyslexia. Although a dyslexic child enjoys and benefits from being read
to, the child might avoid reading aloud to the parent or reading independently.
Dyslexia may coexist with attention-deficit/hyperactivity disorder (see
Chapter 49 ); this comorbidity has been documented in both referred samples
(40% comorbidity) and nonreferred samples (15% comorbidity).

Diagnosis
A large achievement gap between typical and dyslexic readers is evident as early
as 1st grade and persists (Fig. 50.3 ). These findings provide strong evidence and
impetus for early screening and identification of and early intervention for young
children at risk for dyslexia. One source of potentially powerful and highly
accessible screening information is the teacher's judgment about the child's
reading and reading-related skills. Evidence-based screening can be carried out
as early as kindergarten, and also in grades 1-3, by the child's teacher. The
teachers' responses to a small set of questions (10-12 questions) predict a pool of
children who are at risk for dyslexia with a high degree of accuracy. Screening
takes less than 10 minutes, is completed on a tablet, and is extremely efficient
and economical. Children found to be at-risk will then have further assessment
and, if diagnosed as dyslexic, should receive evidence-based intervention.
 FIG. 50.3 Reading from grades 1 through 9 in typical and dyslexic readers. The
achievement gap between typical and dyslexic readers is evident as early as 1st grade
and persists through adolescence. (Adapted from Ferrer E, Shaywitz BA, Holahan JM, et
al: Achievement gap in reading is present as early as first grade and persists through
adolescence, J Pediatr 167:1121–1125, 2015.)

Dyslexia is a clinical diagnosis, and history is especially critical. The clinician

seeks to determine through history, observation, and psychometric assessment, if
there are unexpected difficulties in reading (based on the person's intelligence,
chronological/grade, level of education or professional status) and associated
linguistic problems at the level of phonologic processing. No single test score is
pathognomonic of dyslexia. The diagnosis of dyslexia should reflect a thoughtful
synthesis of all clinical data available.
Dyslexia is distinguished from other disorders that can prominently feature
reading difficulties by the unique, circumscribed nature of the phonologic deficit,
one that does not intrude into other linguistic or cognitive domains. A core
assessment for the diagnosis of dyslexia in children includes tests of language,
particularly phonology; reading, including real and pseudowords; reading
fluency; spelling; and tests of intellectual ability. Additional tests of memory,
general language skills, and mathematics may be administered as part of a more
comprehensive evaluation of cognitive, linguistic, and academic function. Some
schools use a response to intervention (RtI) approach to identifying reading
disabilities (see Chapter 51.1 ). Once a diagnosis has been made, dyslexia is a
permanent diagnosis and need not be reconfirmed by new assessments.
 For informal screening, in addition to a careful history, the primary care
physician in an office setting can listen to the child read aloud from the child's
own grade-level reader. Keeping a set of graded readers available in the office
serves the same purpose and eliminates the need for the child to bring in
schoolbooks. Oral reading is a sensitive measure of reading accuracy and
fluency. The most consistent and telling sign of a reading disability in an
accomplished young adult is slow and laborious reading and writing. In
attempting to read aloud, most children and adults with dyslexia display an
effortful approach to decoding and recognizing single words, an approach in
children characterized by hesitations, mispronunciations, and repeated attempts
to sound out unfamiliar words. In contrast to the difficulties they experience in
decoding single words, persons with dyslexia typically possess the vocabulary,
syntax, and other higher-level abilities involved in comprehension.
The failure either to recognize or to measure the lack of fluency in reading is
perhaps the most common error in the diagnosis of dyslexia in older children and
accomplished young adults. Simple word identification tasks will not detect
dyslexia in a person who is accomplished enough to be in honors high school
classes or to graduate from college or obtain a graduate degree. Tests relying on
the accuracy of word identification alone are inappropriate to use to diagnose
dyslexia because they show little to nothing of the struggle to read. Because they
assess reading accuracy but not automaticity (speed), the types of reading tests
used for school-age children might provide misleading data on bright
adolescents and young adults. The most critical tests are those that are timed ;
they are the most sensitive in detecting dyslexia in a bright adult. Few
standardized tests for young adult readers are administered under timed and
untimed conditions; the Nelson-Denny Reading Test is an exception. The helpful
Test of Word Reading Efficiency (TOWRE) examines simple word reading under
timed conditions. Any scores obtained on testing must be considered relative to
peers with the same degree of education or professional training.

Management
The management of dyslexia demands a life-span perspective. Early in life the
focus is on remediation of the reading problem. Applying knowledge of the
importance of early language, including vocabulary and phonologic skills, leads
to significant improvements in children's reading accuracy, even in predisposed
children. As a child matures and enters the more time-demanding setting of
middle and then high school, the emphasis shifts to the important role of
providing accommodations. Based on the work of the National Reading Panel,
evidence-based reading intervention methods and programs are identified.
Effective intervention programs provide systematic instruction in 5 key areas:
phonemic awareness, phonics, fluency, vocabulary, and comprehension
strategies. These programs also provide ample opportunities for writing, reading,
and discussing literature.
Taking each component of the reading process in turn, effective interventions
improve phonemic awareness: the ability to focus on and manipulate phonemes
(speech sounds) in spoken syllables and words. The elements found to be most
effective in enhancing phonemic awareness , reading, and spelling skills
include teaching children to manipulate phonemes with letters; focusing the
instruction on 1 or 2 types of phoneme manipulations rather than multiple types;
and teaching children in small groups. Providing instruction in phonemic
awareness is necessary but not sufficient to teach children to read. Effective
intervention programs include teaching phonics , or making sure that the
beginning reader understands how letters are linked to sounds (phonemes) to
form letter-sound correspondences and spelling patterns. The instruction should
be explicit and systematic; phonics instruction enhances children's success in
learning to read, and systematic phonics instruction is more effective than
instruction that teaches little or no phonics or teaches phonics casually or
haphazardly. Important but often overlooked is starting children on reading
connected text early on, optimally at or near the beginning of reading instruction.
Fluency is of critical importance because it allows the automatic, rapid
recognition of words, and while it is generally recognized that fluency is an
important component of skilled reading, it has proved difficult to teach.
Interventions for vocabulary development and reading comprehension are not as
well established. The most effective methods to teach reading comprehension
involve teaching vocabulary and strategies that encourage active interaction
between the reader and the text. Emerging science indicates that it is not only
teacher content knowledge but the teacher's skill in engaging the student and
focusing the student's attention on the reading task at hand that is required for
effective instruction.
For those in high school, college, and graduate school, provision of
accommodations most often represents a highly effective approach to dyslexia.
Imaging studies now provide neurobiologic evidence of the need for extra time
for dyslexic students; accordingly, college students with a childhood history of
dyslexia require extra time in reading and writing assignments as well as
examinations. Many adolescent and adult students have been able to improve
their reading accuracy, but without commensurate gains in reading speed. The
accommodation of extra time reconciles the individual's often high cognitive
ability and slow reading, so that the exam is a measure of that person's ability
rather than his disability. Another important accommodation is teaching the
dyslexic student to listen to texts. Excellent text-to-speech programs and apps
available for Apple and Android systems include Voice Dream Reader,
Immersive Reader (in OneNote as part of Microsoft Office), Kurzweil Firefly,
Read & Write Gold, Read: OutLoud, and Natural Reader. Voice-to-text programs
are also helpful, often part of the suite of programs as well as the popular Dragon
Dictate. Voice to text is found on many smartphones. Other helpful
accommodations include the use of laptop computers with spelling checkers,
access to lecture notes, tutorial services, and a separate quiet room for taking
tests.
In addition, the impact of the primary phonologic weakness in dyslexia
mandates special consideration during oral examinations so that students are not
graded on their lack of glibness or speech hesitancies but on their content
knowledge. Unfortunately, speech hesitancies or difficulties in word retrieval
often are wrongly confused with insecure content knowledge. The major
difficulty in dyslexia, reflecting problems accessing the sound system of spoken
language, causes great difficulty learning a 2nd language. As a result, an often-
necessary accommodation is a waiver or partial waiver of the foreign language
requirement; the dyslexic student may enroll in a course on the history or culture
of a non–English-speaking country.

Prognosis
Application of evidence-based methods to young children (kindergarten to grade
3), when provided with sufficient intensity and duration, can result in
improvements in reading accuracy and, to a much lesser extent, fluency. In older
children and adults, interventions result in improved accuracy, but not an
appreciable improvement in fluency. Accommodations are critical in allowing
the dyslexic child to demonstrate his or her knowledge. Parents should be
informed that with proper support, dyslexic children can succeed in a range of
future occupations that might seem out of their reach, including medicine, law,
journalism, and writing.
Bibliography
Ferrer E, Shaywitz BA, Holahan JM, et al. Uncoupling of
reading and IQ over time: empirical evidence for a definition
of dyslexia. Psychol Sci . 2010;21(1):93–101.
Ferrer E, Shaywitz BA, Holahan JM, et al. Achievement gap in
reading is present as early as first grade and persists through
adolescence. J Pediatr . 2015;167:1121–1125.
Herrera-Araujo D, Shaywitz BA, Holahan JM, et al. Evaluating
willingness to pay as a measure of the impact of dyslexia in
adults. J Benefit Cost Anal . 2017;8(1):4–48.
Hulme C, Snowling MJ. Reading disorders and dyslexia. Curr
Opin Pediatr . 2016;28:731–735.
National Reading Panel. Teaching children to read: an evidence
based assessment of the scientific research literature on
reading and its implications for reading instruction, NIH Pub
No 00-4754 . US Department of Health and Human Services,
Public Health Service, National Institutes of Health, National
Institute of Child Health and Human Development: Bethesda,
MD; 2000.
Romberg F, Shaywitz BA, Shaywitz SE. How should medical
schools respond to students with dyslexia? AMA J Ethics .
2016;18(10):975–984.
Shaywitz S. Overcoming dyslexia: a new and complete science-
based program for reading problems at any level . Alfred A
Knopf: New York; 2003.
Shaywitz SE: Shaywitz DyslexiaScreen. The Shaywitz
DyslexiaScreen is an efficient, reliable, and user-friendly
dyslexia test for K-1. This screening tool identifies students
who are at risk for dyslexia. Available from Pearson Clinical.
Shaywitz SE, Shaywitz BA. Dyslexia (specific reading
disability). Biol Psychiatry . 2005;57:1301–1309.
Shaywitz BA, Weiss LG, Saklofske DH, Shaywitz SE.
 Translating scientific progress in dyslexia into 21st century
diagnosis and interventions. Weiss LG, Saklofske DH,
Holdnack JA, Prifitera A. WISC-V Clinical use and
interpretation: a scientist-practitioner perspective . Elsevier:
San Diego; 2016:269–286.
Shaywitz S, Shaywitz B, Wietecha L, et al. Effect of
atomoxetine treatment on reading and phonological skills in
children with dyslexia or attention-deficit/hyperactivity
disorder and comorbid dyslexia in a randomized, placebo-
controlled trial. J Child Adolesc Psychopharmacol .
2017;27(1):19–28.
US Senate Resolution 576. Calling on Congress, schools, and
State and local educational agencies to recognize the
significant educational implications of dyslexia that must be
addressed . [Washington, DC] 2016 [114th Congress, 2nd
Session ed].
CHAPTER 51

Math and Writing Disabilities

51.1
Math Disabilities
Kenneth L. Grizzle

Keywords
dyscalculia
math disability
Individual with Disabilities Education Act
IDEA
individualized education plan
IEP
response to intervention
specific learning disorder with impairment in mathematics

Data from the U.S. National Center for Educational Statistics for 2009 showed
that 69% of U.S. high school graduates had taken algebra 1, 88% geometry, 76%
algebra 2/trigonometry, and 35% precalculus. These percentages are
considerably higher than those for 20 years earlier. However, concerns remain
about the limited literacy level in mathematics for children, adolescents, and
those entering the workforce; poor math skills predict numerous social,
employment, and emotional challenges. The need for number and math literacy
extends beyond the workplace and into daily lives, and weaknesses in this area
can negatively impact daily functioning. Research into the etiology and
treatment of math disabilities falls far behind the study of reading disabilities
(see Chapter 50 ). Therefore the knowledge needed to identify, treat, and
minimize the impact of math challenges on daily functioning and education is
limited.

Math Learning Disability Defined

Understanding learning challenges associated with mathematics requires a basic
appreciation of domain-specific terminology and operations. The Diagnostic and
Statistical Manual for Mental Disorders, Fifth Edition (DSM-5) has published
diagnostic criteria for learning disorders. Specific types of learning challenges
are subsumed under the broad term of specific learning disorder (SLD) . The
DSM identifies the following features of a SLD with an impairment in math:
difficulties mastering number sense, number facts, or fluent calculation and
difficulties with math reasoning. Symptoms must be present for a minimum of 6
mo and persist despite interventions to address the learning challenges. Number
sense refers to a basic understanding of quantity, number, and operations and is
represented as nonverbal and symbolic. Examples of number sense include an
understanding that each number is 1 more or 1 less than the previous or
following number; knowledge of number words and symbols; and the ability to
compare the relative magnitude of numbers and perform simple arithmetic
calculations.
The DSM-5 definition can be contrasted with an education-defined learning
disability in mathematics . Two math-related areas are identified as part of the
Individuals with Disabilities Education Act (IDEA): mathematics calculation
and mathematics problem solving. Operationally, this is reflected in age-level
competency in arithmetic and math calculation, word problems, interpreting
graphs, understanding money and time concepts, and applying math concepts to
solve quantitative problems. The federal government allows states to choose the
way a learning disability (LD) is identified if the procedure is “research based.”
Referred to specifically in IDEA as methods for identifying an LD are a
discrepancy model and “use of a process based on the child's response to
scientific, research-based intervention.” The former refers to identifying a LD
based on a pronounced discrepancy between intellectual functioning and
academic achievement. The latter, referred to as a response to intervention
(RtI) model, requires school systems to screen for a disability, intervene using
empirically supported treatments for the identified disability, closely monitor
progress, and make necessary adjustments to the intervention as needed. If a
child is not responding adequately, a multidisciplinary team evaluation is used to
develop an individualized educational plan (IEP) .
It is important that primary care providers understand the RtI process because
many states require or encourage this approach to identifying LDs. Confusion
can be avoided by helping concerned parents understand that a school may
review their child's records, screen the skills of concern, and provide
intervention with close progress monitoring, before initiating the process for an
IEP. Traditional psychoeducation testing (IQ and achievement) may only be
completed if a child has not responded well to specific interventions. The RtI
approach is a valuable, empirically supported way to approach and identify a
potential learning disability, but very different from a medical approach to
diagnosis and treatment.

Terminology
The term dyscalculia , often used in medicine and research but seldom used by
educators, is reserved for children with a SLD in math when there is a pattern of
deficits in learning arithmetic facts and accurate, fluent calculations. The term
math learning disability (MLD ) is used generically here, with dyscalculia used
when limiting the discussion to children with deficient math calculation skills. A
distinction is also made between children with a MLD and those who are low
achieving (LA) in math; both groups have received considerable research
focus. Although not included in either definition above, research into math
deficits typically requires that individuals identified with MLD have math
achievement scores below the 10th percentile across multiple grade levels. These
children start out poorly in math and continue poor performance across grades,
despite interventions. LA math students consistently score below the 25th
percentile on math achievement tests across grades, but show more typical entry-
level math skills.

Epidemiology
Prevalence
Depending on how MLD is defined and assessed, the prevalence varies. Based
on findings from multiple studies, approximately 7% of children will show a
MLD profile before high school graduation. An additional 10% of students will
be identified as LA. Because research in the area typically requires that
individuals show deficits for consecutive years, the respective prevalence
estimates are lower than the 10th percentile cutoff for being identified as MLD
or the 25th percentile cutoff for being identified as LA. It is not unusual for
children to score below the criterion one year and above the criterion in
subsequent years. These children do not show the same cognitive deficits
associated with a MLD. Unlike dyslexia, boys are at greater risk to experience
MLD. This is found in epidemiologic research in the United States (risk ratio,
1.6-2.2 : 1) and various European countries.

Risk Factors
Genetics
The heritability of math skills is estimated to be approximately 0.50. The
heritability or genetic influence on math skills is consistent across the continuum
from high to low math skills. This research emphasizes that although math skills
are learned across time, the stability of math performance is the result of genetic
influences. Math heritability appears to be the product of multiple genetic
markers, each having a small effect.

Medical/Genetic Conditions
Numerous genetic syndromes are associated with math problems. Although most
children with fragile X syndrome have an intellectual disability (ID),
approximately 50% of girls with the condition do not. Of those without an ID,
≥75% have a math disability by the end of 3rd grade and are already scoring
below average in mathematics in kindergarten and 1st grade. For girls with
fragile X MLD, weak working memory seems to play an important role. The
frequency of MLD in girls with Turner syndrome (TS) is the same as found in
girls with fragile X syndrome. A consistent finding is girls with TS complete
math calculations at significantly slower speed than typically developing
students. Although girls with TS have weak calculation skills, their ability to
complete math problems not requiring explicit calculation is similar to that of
their peers. The percentage of children with the 22q11.2 deletion syndrome
(22q11.2ds) with MLD is not clear. Younger children with this genetic condition
(6-10 yr old) showed similar number sense and calculation skills as typically
developing children but weaker math problem solving. Older children with
22q11.2ds showed slower speed in their general number sense and calculations,
but accuracy was maintained. Weak counting skills and magnitude comparison
have been found in this group of children, suggesting weak visual-spatial
processing. Children with myelomeningocele are at greater risk for math
difficulties than their unaffected peers. Almost 30% of these children have MLD
without an additional diagnosed learning disorder, and >50% have both math
and reading learning disorders. While broad, deficits are most pronounced in
speed of math calculation and written computation.

Comorbidities
It is estimated that 30–70% of those with MLD will also have reading disability.
This is especially important because children with MLD are less likely to be
referred for additional educational assistance and intervention than students with
reading problems. Unfortunately, children identified with both learning
challenges perform poorer across psychosocial and academic measures than
children with MLD alone. Having a MLD places a child at greater risk for not
only other learning challenges but also psychiatric disorders, including attention-
deficit/hyperactivity disorder, oppositional defiant disorder, conduct disorder,
generalized anxiety disorder, and major depressive disorder. Individuals with
MLD have been found to have increased social isolation and difficulties
developing social relationships in general.

Causes of Math Learning Disability

There is a consensus that individuals with MLD are a heterogeneous group, with
multiple potential broad and specific deficits driving their learning difficulties.
Research into the causes of MLD has focused on math-specific processes and
broad cognitive deficits, with an appreciation that these two factors are not
always independent.

Broad Cognitive Processes

Intelligence
Intelligence affects learning, but if intellectual functioning were the primary
driver of poor math performance, the math skills of low-IQ children would be
similar or worse than individuals with MLD. On the contrary, children with
MLD have significantly poorer math achievement than children with low IQ.
Children with MLD have severe deficits in math not accounted for by their
cognitive functioning. Individuals with lower cognition may have difficulty
learning mathematics, but their math skills are likely to be commensurate with
their intelligence.

Working Memory
Working memory refers to the ability to keep information in mind while using
the information in other mental processes. Working memory is composed of 3
core systems: the central executive, the language-related phonologic loop, and
the visual-based sketch pad. The central executive coordinates the functioning of
the other two systems. All three play a role in various aspects of learning and in
the development and application of math skills in particular; children with MLD
have shown deficits in each area.

Processing Speed
Individuals with MLD are often slower to complete math problems than their
typically developing peers, a result of their poor fact retrieval rather than broader
speed of processing deficits. However, young children later identified with a
MLD when beginning school have number-processing speed that is considerably
slower than same-age same-grade peers.

Math-Specific Processes
Procedural Errors
The type of errors made by children with a MLD are typical for any child, the
difference being that children with a learning disability show a 2-3 yr lag in
understanding the concept. An example of a common error a 1st grade child with
a MLD might make when “counting on” is to undercount: “6 + 2= ?;” “6, 7”
rather than starting at 6 and counting an additional 2 numbers. As children with
math deficits get older, it is common to subtract a larger number from a smaller
number. For example, in the problem “63 − 29 = 46,” the child makes the
mistake of subtracting 3 from 9. Another common error is not decreasing the
number in the 10s column when borrowing: “64 − 39 = 35.” For both adding and
subtracting, there is a lack of understanding of the commutative property of
numbers and a tendency to use repeated addition rather than fact retrieval. It is
not that children with a MLD do not develop these skills, it is that they develop
them much later than their peers, thereby making the transition to complicated
math concepts much more challenging.

Memory for Math Facts

Committing math facts to or retrieving facts from memory have consistently
been found to be problematic for children with MLD. Weak fact encoding or
retrieval alone do not determine a MLD diagnosis. Many math curricula in the
United States do not include development of math facts as a part of the
instructional process, resulting in children not knowing basic facts.
Unlike dyslexia, in which deficits have been isolated and identified as causal
(see Chapter 50 ), factors involved in the development of a MLD are much more
heterogeneous. Alone, none of the processes previously outlined fully accounts
for MLD, although all have been implicated as problematic for those struggling
with math.

Treatment and Interventions

The most effective interventions for MLD are those that include explicit
instruction on solving specific types of problems and that take place over several
weeks to several months. Skill-based instruction is a critical component; general
math problem solving will not carry over across various math skills, unless the
skill is part of a more complex math concept. Clear, comprehensive guidelines
for effective interventions for students struggling with math have been provided
by the U.S. Department of Education in the form of a Practice Guide released
through the What Works Clearinghouse. This document gives excellent direction
in the identification and treatment of children with math difficulties in the
educational system. Although not intended for medical personnel or parents, the
guide is available free of charge and can be helpful for parents when talking to
teachers about their child's learning. Table 51.1 lists additional resources for
parents concerned about their young child's development of math facts.
Table 51.1
Parent Resources for the Child With Math
Learning Disability
Let's Talk About Math . Available from:
http://www.zerotothree.org/parenting-resources/early-math-video-series .
Accessed January 2, 2017.
Mixing in Math . Available from:
https://mixinginmath.terc.edu/aboutMiM/what_isMiM.php . Accessed
January 2, 2017.
PBS Parents. Math resources available to parents through the Public
Broadcasting Service website. Accessed January 28, 2017:
http://www.pbs.org/parents/earlymath/index.html
http://www.pbs.org/parents/education/math/
US Department of Education: Helping your child learn mathematics .
Available from:
https://www2.ed.gov/parents/academic/help/math/index.html . Accessed
January 28, 2017.

Awareness that most public school systems have implemented some form of a
RtI to identify learning disabilities allows the primary care physician to
encourage parents to return to the school seeking an intervention to address their
child's concern. Receiving special education services in the form of an IEP may
be necessary for some children. However, the current approach to identifying
children with a learning disability allows school systems to intervene earlier,
when problems arise, and potentially avoid the need for an IEP. Pediatricians
with patients whose parents have received feedback from school with any of the
risk factors outlined in Table 51.2 should encourage the parents to discuss an
intervention plan with the child's teacher.
Table 51.2
Risk Factors for a Specific Learning
Disability Involving Mathematics
The child is at or below the 20th percentile in any math area, as reflected
by standardized testing or ongoing measures of progress monitoring.
The teacher expresses concerns about the child's ability to “take the next
step” in math.
 There is a positive family history for math learning disability (this alone
will not initiate an intervention).
Parents think they have to “reteach” math concepts to their child.

Bibliography
Bartelet D, Ansari D, Vaessen A, Blomert L. Cognitive subtypes
of mathematics learning difficulties in primary education. Res
Dev Disabil . 2014;35(3):657–670.
Chodura S, Kuhn JT, Holling H. Interventions for children with
mathematical difficulties: a meta-analysis. Z Psychol .
2015;223(2):129–144.
Docherty SJ, Davis OSP, Kovas Y, et al. Genome-wide
association study identifies multiple loci associated with
mathematics ability and disability. Genes Brain Behav .
2010;9:234–247.
Geary DC. Mathematical cognition deficits in children with
learning disabilities and persistent low achievement: a five-
year prospective study. J Educ Psychol . 2012;104(1):206–
223.
Kaufman L, Mazzocco MM, Dowker A, et al. Dyscalculia from
a developmental and differential perspective. Front Psychol .
2013;4:1–5.
Kucian K. Developmental dyscalculia and the brain. Berch DB,
Geary DC, Koepke KM. Development of mathematical
cognition: neural substrates and genetic influences . Elsevier:
New York; 2016:165–193.
Mazzocco M. Mathematics awareness month: why should
pediatricians be aware of mathematics and numeracy? J Dev
Behav Pediatr . 2016;37:251–253.
Mazzocco MM, Quintero AI, Murphy MM, McCloskey M.
Genetic syndromes as model pathways to mathematical
learning difficulties: fragile X, Turner and 22q deletion
 syndromes. Berch DB, Geary DC, Koepke KM. Development
of mathematical cognition: neural substrates and genetic
influences . Elsevier: New York; 2016:325–357.
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ability: a behavioral genetic approach. Berch DB, Geary DC,
Koepke KM. Development of mathematical cognition: neural
substrates and genetic influences . Elsevier: New York;
2016:299–324.
Shin MS, Bryant DP. A synthesis of mathematical and cognitive
performances of students with mathematics learning
disabilities. J Learn Disabil . 2015;48:96–112.

51.2
Writing Disabilities
Kenneth L. Grizzle

Keywords
dysgraphia
transcription
specific language impairment
pragmatic language
higher-level language
executive functions
working memory
504 plan
individual education plan
Oral language is a complex process that typically develops in the absence of
formal instruction. In contrast, written language requires instruction in
acquisition (word reading), understanding (reading comprehension), and
expression (spelling and composition). Unfortunately, despite reasonable
pedagogy, a subset of children struggle with development in one or several of
these areas. The disordered output of written language is currently referred to
within the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition
(DSM-5) as a specific learning disorder with impairment in written
expression (Table 51.3 ).
Table 51.3
DSM-5 Diagnostic Criteria for Specific
Learning Disability With Impairment in
Written Expression
A. Difficulties learning and using academic skills that have persisted for at
least 6 mo, despite the provision of interventions that target those
difficulties.
Difficulties with written expression (e.g., makes multiple
grammatical or punctuation errors within sentences; employs
poor paragraph organization; written expression of ideas lacks
clarity).
B. The affected academic skills are substantially and quantifiably below those
expected for the individual's chronological age, and cause significant
interference with academic or occupational performance, or with activities
of daily living, as confirmed by individually administered standardized
achievement measures and comprehensive clinical assessment. For
individuals age 17 yr and older, a documented history of impairing learning
difficulties may be substituted for the standardized assessment.
C. The learning difficulties begin during school-age years but may not
become fully manifest until the demands for those affected academic skills
exceed the individual's limited capacities (e.g., as in timed tests, reading or
writing lengthy complex reports for a tight deadline, excessively heavy
academic loads).
D. The learning difficulties are not better accounted for by intellectual
disabilities, uncorrected visual or auditory acuity, other mental or
 neurologic disorders, psychosocial adversity, lack of proficiency in the
language of academic instruction, or inadequate educational instruction.

315.2 (F81.81) With impairment in written expression:

Spelling accuracy
Grammar and punctuation accuracy
Clarity or organization of written expression
Specify current severity:
Mild: Some difficulties learning skills in 1 or 2 academic domains, but of
mild enough severity that the individual may be able to compensate or
function well when provided with appropriate accommodations or
support services, especially during the school years.
Moderate: Marked difficulties learning skills in ≥1 academic domain(s),
so that the individual is unlikely to become proficient without some
intervals of intensive and specialized teaching during the school years.
Some accommodations or supportive services at least part of the day at
school, in the workplace, or at home may be needed to complete activities
accurately and efficiently.
Severe: Severe difficulties learning skills, affecting several academic
domains, so that the individual is unlikely to learn those skills without
ongoing intensive individualized and specialized teaching for most of the
school years. Even with an array of appropriate accommodations or
services at home, at school, or in the workplace, the individual may not
be able to complete all activities efficiently.

Adapted from the Diagnostic and Statistical Manual of Mental Disorders, Fifth
Edition, (Copyright 2013). American Psychiatric Association, pp 66–67.

Various terminology has been used when referring to individuals with writing
deficits; this subchapter uses the term impairment in written expression (IWE)
rather than “writing disorder” or “disorder of written expression.” Dysgraphia is
often used when referring to children with writing problems, sometimes
synonymously with IWE, although the two are related but distinct conditions.
Dysgraphia is primarily a deficit in motor output (paper/pencil skills), and IWE
is a conceptual weakness in developing, organizing, and elaborating on ideas in
writing.
 The diagnoses of a IWE and dysgraphia are made largely based on
phenotypical presentation; spelling, punctuation, grammar, clarity, and
organization are factors to consider with IWE concerns. Aside from these
potentially weak writing characteristics, however, no other guidelines are
offered. Based on clinical experience and research into the features of writing
samples of children with disordered writing skills, one would expect to see
limited output, poor organization, repetition of content, and weak sentence
structure and spelling, despite the child taking considerable time to produce a
small amount of content. For those with comorbid dysgraphia, the legibility of
their writing product will also be poor, sometimes illegible.

Epidemiology
The incidence of IWE is estimated at 6.9–14.7%, with the relative risk for IWE
2-2.9 times higher for boys than girls. One study covering three U.S. geographic
regions found considerably higher rates of IWE in the Midwest and Southeast
than in the West.
The risk for writing problems is much greater among select populations;
>50% of children with oral language disorders reportedly have IWE. The
relationship between attention-deficit/hyperactivity disorder (ADHD) and
learning disorders in general is well established, including IWE estimates in the
60% range for the combined and inattentive presentations of ADHD. Because of
the importance of working memory and other executive functions in the writing
process, any child with weakness in these areas will likely find the writing
process difficult (see Chapter 48 ).

Skill Deficits Associated With Impaired

Writing
Written language, much like reading, occurs along a developmental trajectory
that can be seamless as children master skills critical to the next step in the
process. Mastery of motor control that allows a child to produce letters and letter
sequences frees up cognitive energy to devote to spelling words and eventually
stringing words into sentences, paragraphs, and complex composition. Early in
the development of each individual skill, considerable cognitive effort is
required, although ideally the lower-level skills of motor production, spelling,
punctuation, and capitalization (referred to as writing mechanics or writing
conventions ) will gradually become automatic and require progressively less
mental effort. This effort can then be devoted to higher-level skills, such as
planning, organization, application of knowledge, and use of varied vocabulary.
For children with writing deficits, breakdowns can occur at one, some, or every
stage.

Transcription
Among preschool and primary grade children, there is a wide range of what is
considered “developmentally typical” as it relates to letter production and
spelling. However, evidence indicates that poor writers in later grades are slow
to produce letters and write their name in preschool and kindergarten. Weak
early spelling and reading skills (letter identification and phonologic awareness;
see Chapter 50 ) and weak oral language have also been found to predict weak
writing skills in later elementary grades. Children struggling to master early
transcription skills tend to write slowly, or when writing at reasonable speed,
the legibility of their writing degrades. Output in quantity and variety is limited,
and vocabulary use in poor spellers is often restricted to words they can spell.
As children progress into upper elementary school and beyond, a new set of
challenges arise. They are now expected to have mastered lower-level
transcription skills, and the focus turns to the application of these skills to more
complex text generation. In addition to transcription, this next step requires the
integration of additional cognitive skills that have yet to be tapped by young
learners.

Oral Language
Language, although not speech, has been found to be related to writing skills.
Writing difficulties are associated with deficits in both expression and
comprehension of oral language. Writing characteristics of children with specific
language impairment (SLI) can differ from their unimpaired peers early in the
school experience, and persist through high school (see Chapter 52 ). In
preschool and kindergarten, as a group, children with language disorders show
poorer letter production and ability to print their name. Poor spelling and weak
vocabulary also contribute to the poor writing skills. Beyond primary grades, the
written narratives of SLI children tend to be evaluated as “lower quality with
poor organization” and weaker use of varied vocabulary.
Pragmatic language and higher-level language deficits also negatively impact
writing skills. Pragmatic language refers to the social use of language,
including, though not limited to greeting and making requests; adjustments to
language used to meet the need of the situation or listener; and following
conversation rules verbally and nonverbally. Higher-level language goes
beyond basic vocabulary, word form, and grammatical skills and includes
making inferences, understanding and appropriately using figurative language,
and making cause-and-effect judgments. Weaknesses in these areas, with or
without intact foundational language, can present challenges for students in all
academic areas that require writing. For example, whether producing an analytic
or narrative piece, the writer must understand the extent of the reader's
background knowledge and in turn what information to include and omit, make
an argument for a cause-and-effect relationship, and use content-specific
vocabulary or vocabulary rich in imagery and nonliteral interpretation.

Executive Functions
Writing is a complicated process and, when done well, requires the effective
integration of multiple processes. Executive functions (EFs) are a set of skills
that include planning, problem solving, monitoring and making adjustments as
needed (see Chapter 48 ). Three recursive processes have consistently been
reported as involved in the writing process: translation of thought into written
output, planning, and reviewing. Coming up with ideas, while challenging for
many, is simply the first step when writing a narrative (story). Once an idea has
emerged, the concept must be developed to include a plot, characters, and story
line and then coordinated into a coherent whole that is well organized and flows
from beginning to end. Even if one develops ideas and begins to write them
down, persistence is required to complete the task, which requires self-
regulation. Effective writers rely heavily on EFs, and children with IWE struggle
with this set of skills. Poor writers seldom engage in the necessary planning and
struggle to self-monitor and revise effectively.

Working Memory
Working memory (WM) refers to the ability to hold, manipulate, and store
information for short periods. The more space available, the more memory can
be devoted to problem solving and thinking tasks. Nevertheless, there is limited
space in which information can be held, and the more effort devoted to one task,
the less space is available to devote to other tasks. WM has consistently been
shown to play an important role in the writing process, because weak WM limits
the space available. Further, when writing skills that are expected to be
automatic continue to require effort, precious memory is required, taking away
what would otherwise be available for higher-level language.
The Simple View of Writing is an approach that integrates each of the 4 ideas
just outlined to describe the writing process (Fig. 51.1 ). At the base of the
triangle are transcription and executive functions, which support, within WM,
the ability to produce text. Breakdowns in any of these areas can lead to poor
writing, and identifying where the deficit(s) are occurring is essential when
deciding to treat the writing problem. For example, children with weak
graphomotor skills (e.g., dysgraphia) must devote considerable effort to the
accurate production of written language, thereby increasing WM use devoted to
lower-level transcription and limiting memory that can be used for developing
discourse. The result might be painfully slow production of a legible story, or a
passage that is largely illegible. If, on the other hand, a child's penmanship and
spelling have developed well, but their ability to persist with challenging tasks or
to organize their thoughts and develop a coordinated plan for their paper is
limited, one might see very little information written on the paper despite
considerable time devoted to the task. Lastly, even when skills residing at the
base of this triangle are in place, students with a language disorder will likely
produce text that is more consistent with their language functioning than their
chronological grade or age (Fig. 51.1 ).
 FIG. 51.1 Simple view of writing. (From Berninger VW: Preventing written expression
disabilities through early and continuing assessment and intervention for handwriting
and/or spelling problems: research into practice. In Swanson HL, Harris KR, Graham S,
editors: Handbook of learning disabilities, New York, 2003, The Guilford Press.)

Treatment
Poor writing skills can improve with effective treatment. Weak graphomotor
skills may not necessarily require intervention from an occupational therapist
(OT), although Handwriting Without Tears is a curriculum frequently used by
OTs when working with children with poor penmanship. An empirically
supported writing program has been developed by Berninger, but it is not widely
used inside or outside school systems (PAL Research-Based Reading and Writing
Lessons). For children with dysgraphia, lower-level transcription skills should be
emphasized to the point of becoming automatic. The connection between
transcription skills and composition should be included in the instructional
process; that is, children need to see how their work at letter production is
related to broader components of writing. Further, because of WM constraints
that frequently impact the instructional process for students with learning
disorders, all components of writing should be taught within the same lesson.
Explicit instruction of writing strategies combined with implementation and
coaching in self-regulation will likely produce the greatest gains for students
with writing deficits. Emphasis will vary depending on the deficit specific to the
child. A well-researched and well-supported intervention for poor writers is self-
regulated strategy development (SRSD) . The 6 stages in this model include
developing and activating a child's background knowledge; introducing and
discussing the strategy that is being taught; modeling the strategy for the student;
assisting the child in memorization of the strategy; supporting the child's use of
the strategy during implementation; and independent use of the strategy. SRSD
can be applied across various writing situations and is supported until the student
has developed mastery. The model can emphasize or deemphasize the areas most
needed by the child.

Educational Resources
Children with identified learning disorders can potentially qualify for formal
education programming through special education or a section 504 plan. Special
education is guided on a federal level by the Individual with Disabilities
Education Act (IDEA) and includes development of an individual education
plan (see Chapter 48 ). A 504 plan provides accommodations to help children
succeed in the regular classroom. Accommodations that might be provided to a
child with IWE, through an IEP or a 504 plan, include dictation to a scribe when
confronted with lengthy writing tasks, additional time to complete exams that
require writing, and use of technology such as keyboarding, speech-to-text
software, and writing devices that record teacher instruction. When
recommending that parents pursue assistive technology for their child as a
potential accommodation, the physician should emphasize the importance of
instruction to mastery of the device being used. Learning to use technology
effectively requires considerable time and is initially likely to require additional
effort, which can result in frustration and avoidance.

Bibliography
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handwriting to children with writing disabilities. Perspect
Lang Learn Educ . 2014;21:114–126.
Berninger VW. Preventing written expression disabilities
through early and continuing assessment and intervention for
handwriting and/or spelling problems: research into practice.
Swanson HL, Harris KR, Graham S. Handbook of learning
 disabilities . The Guilford Press: New York; 2003:35–363.
Berninger VW. Process assessment of the learner (PAL):
research-based reading and writing lessons . Psychological
Corporation: San Antonio, TX; 2003.
Berninger VW. Interdisciplinary frameworks for schools: best
professional practices for serving the needs of all students .
American Psychological Association: Washington, DC; 2015.
Berninger VW, May MO. Evidence-based diagnosis and
treatment for specific learning disabilities involving
impairments in written and/or oral language. J Learn Disabil
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Dockrell JE. Developmental variations in the production of
written text: challenges for students who struggle with
writing. Stone CA, Silliman ER, Ehren BJ, Wallach GP.
Handbook of language and literacy . ed 2. The Guilford
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language impairment on adolescents' written text. Except
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Graham S, Harris KR. Writing better: effective strategies for
teaching students with learning difficulties . Paul H Brookes
Publishing: Baltimore; 2005.
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forgotten learning disability: epidemiology of written-
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adolescence: listening, speaking, reading, writing, and
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the nature of oral and written language problems in the
context of developmental, academic, and phenotypic profiles.
 Top Lang Disord . 2011;31:6–23.
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language impairment and risk for written language disorder: a
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CHAPTER 52

Language Development and

Communication Disorders
Mark D. Simms

Most children learn to communicate in their native language without specific

instruction or intervention other than exposure to a language-rich environment.
Normal development of speech and language is predicated on the infant's ability
to hear, see, comprehend, remember, and socially interact with others. The infant
must also possess sufficient motor skills to imitate oral motor movements.

Normal Language Development

Language can be subdivided into several essential components. Communication
consists of a wide range of behaviors and skills. At the level of basic verbal
ability, phonology refers to the correct use of speech sounds to form words,
semantics refers to the correct use of words, and syntax refers to the appropriate
use of grammar to make sentences. At a more abstract level, verbal skills include
the ability to link thoughts together coherently and to maintain a topic of
conversation. Pragmatic abilities include verbal and nonverbal skills that
facilitate the exchange of ideas, including the appropriate choice of language for
the situation and circumstance and the appropriate use of body language (i.e.,
posture, eye contact, gestures). Social pragmatic and behavioral skills also play
an important role in effective interactions with communication partners (i.e.,
engaging, responding, and maintaining reciprocal exchanges).
It is customary to divide language skills into receptive (hearing and
understanding) and expressive (talking) abilities. Language development usually
follows a fairly predictable pattern and parallels general intellectual development
(Table 52.1 ).
Table 52.1
Normal Language Milestones: Birth to 5 Years

HEARING AND UNDERSTANDING TALKING

BIRTH TO 3 MONTHS
Startles to loud sounds Makes pleasure sounds (cooing, gooing)
Quiets or smiles when spoken to Cries differently for different needs
Seems to recognize your voice and quiets if crying Smiles when sees you
Increases or decreases sucking behavior in response to
sound
4-6 MONTHS
Moves eyes in direction of sounds Babbling sounds more speech-like, with
Responds to changes in tone of your voice many different sounds, including p, b, and m
Notices toys that make sounds Vocalizes excitement and displeasure
Pays attention to music Makes gurgling sounds when left alone and
when playing with you
7 MONTHS TO 1 YEAR
Enjoys games such as peek-a-boo and pat-a-cake Babbling has both long and short groups of
Turns and looks in direction of sounds sounds, such as tata upup bibibibi.
Listens when spoken to Uses speech or noncrying sounds to get and
Recognizes words for common items, such as cup, shoe, keep attention
and juice Imitates different speech sounds
Begins to respond to requests (Come here; Want more?) Has 1 or 2 words (bye-bye, dada, mama),
although they might not be clear
1-2 YEARS
Points to a few body parts when asked Says more words every month
Follows simple commands and understands simple Uses some 1-2 word questions (Where kitty?
questions (Roll the ball; Kiss the baby; Where's your Go bye-bye? What's that?)
shoe?) Puts 2 words together (more cookie, no
Listens to simple stories, songs, and rhymes juice, mommy book)
Points to pictures in a book when named Uses many different consonant sounds at the
beginning of words
2-3 YEARS
Understands differences in meaning (e.g., go–stop, in–on, Has a word for almost everything
big–little, up–down) Uses 2-3 word “sentences” to talk about and
Follows 2-step requests (Get the book and put it on the ask for things
table.) Speech is understood by familiar listeners
most of the time
Often asks for or directs attention to objects
by naming them
3-4 YEARS
Hears you when you call from another room Talks about activities at school or at friends'
Hears television or radio at the same loudness level as homes
other family members Usually understood by people outside the
Understands simple who, what, where, why questions family
Uses a lot of sentences that have ≥4 words
Usually talks easily without repeating
syllables or words
4-5 YEARS
Pays attention to a short story and answers simple Voice sounds as clear as other children's
questions about it Uses sentences that include details (I like to
Hears and understands most of what is said at home and in read my books)
 school Tells stories that stick to a topic
Communicates easily with other children
and adults
Says most sounds correctly except a few,
such as l, s, r, v, z, ch, sh, and th
Uses the same grammar as the rest of the
family
Adapted from American Speech-Language-Hearing Association, 2005.
http://www.asha.org/public/speech/development/chart.htm .

Receptive Language Development

The peripheral auditory system is mature by 26 wk gestation, and the fetus
responds to and discriminates speech sounds. Anatomic asymmetry in the
planum temporale , the structural brain region specialized for language
processing, is present by 31 wk gestation. At birth, the full-term newborn
appears to have functionally organized neural networks that are sensitive to
different properties of language input. The normal newborn demonstrates
preferential response to human voices over inanimate sound and recognizes the
mother's voice, reacting stronger to it than to a stranger's voice. Even more
remarkable is the ability of the newborn to discriminate sentences in their
“native” (mother's) language from sentences in a “foreign” language. In research
settings, infants of monolingual mothers showed a preference for only that
language, whereas infants of bilingual mothers showed a preference for both
exposed languages over any other language.
Between 4 and 6 mo, infants visually search for the source of sounds, again
showing a preference for the human voice over other environmental sounds. By
6 mo, infants can passively follow the adult's line of visual regard, resulting in a
“joint reference” to the same objects and events in the environment. The ability
to share the same experience is critical to the development of further language,
social, and cognitive skills as the infant “maps” specific meanings onto his or her
experiences. By 8-9 mo, the infant can actively show, give, and point to objects.
Comprehension of words often becomes apparent by 9 mo, when the infant
selectively responds to his or her name and appears to comprehend the word
“no.” Social games, such as “peek-a-boo,” “so big,” and waving “bye-bye” can
be elicited by simply mentioning the words. At 12 mo, many children can follow
a simple, 1-step request without a gesture (e.g., “Give it to me”).
Between 1 and 2 yr, comprehension of language accelerates rapidly. Toddlers
can point to body parts on command, identify pictures in books when named,
and respond to simple questions (e.g., “Where's your shoe?”). The 2 yr old is
able to follow a 2-step command, employing unrelated tasks (e.g., “Take off
your shoes, then go sit at the table”), and can point to objects described by their
use (e.g., “Give me the one we drink from”). By 3 yr, children typically
understand simple “wh-” question forms (e.g., who, what, where, why). By 4 yr,
most children can follow adult conversation. They can listen to a short story and
answer simple questions about it. A 5 yr old typically has a receptive vocabulary
of more than 2000 words and can follow 3- and 4-step commands.

Expressive Language Development

Cooing noises are established by 4-6 wk of age. Over the 1st 3 mo of life,
parents may distinguish their infant's different vocal sounds for pleasure, pain,
fussing, tiredness, and so on. Many 3 mo old infants vocalize in a reciprocal
fashion with an adult to maintain a social interaction (“vocal tennis”). By 4 mo,
infants begin to make bilabial (“raspberry”) sounds, and by 5 mo, monosyllables
and laughing are noticeable. Between 6 and 8 mo, polysyllabic babbling
(“lalala” or “mamama”) is heard, and the infant might begin to communicate
with gestures. Between 8 and 10 mo, babbling makes a phonologic shift toward
the particular sound patterns of the child's native language (i.e., they produce
more native sounds than nonnative sounds). At 9-10 mo, babbling becomes
truncated into specific words (e.g., “mama,” “dada”) for their parents.
Over the next several months, infants learn 1 or 2 words for common objects
and begin to imitate words presented by an adult. These words might appear to
come and go from the child's repertoire until a stable group of 10 or more words
is established. The rate of acquisition of new words is approximately 1 new word
per week at 12 mo, but it accelerates to approximately 1 new word per day by 2
yr. The first words to appear are used primarily to label objects (nouns) or to ask
for objects and people (requests). By 18-20 mo, toddlers should use a minimum
of 20 words and produce jargon (strings of word-like sounds) with language-like
inflection patterns (rising and falling speech patterns). This jargon usually
contains some embedded true words. Spontaneous 2-word phrases (pivotal
speech), consisting of the flexible juxtaposition of words with clear intention
(e.g., “Want juice!” or “Me down!”), is characteristic of 2 yr olds and reflects the
emergence of grammatical ability (syntax).
Two-word, combinational phrases do not usually emerge until children have
acquired 50-100 words in their lexicon. Thereafter, the acquisition of new words
accelerates rapidly. As knowledge of grammar increases, there is a proportional
increase in verbs, adjectives, and other words that serve to define the relation
between objects and people (predicates). By 3 yr, sentence length increases, and
the child uses pronouns and simple present-tense verb forms. These 3-5 word
sentences typically have a subject and verb but lack conjunctions, articles, and
complex verb forms. The Sesame Street character Cookie Monster (“Me want
cookie!”) typifies the “telegraphic” nature of the 3 yr old's sentences. By 4-5 yr,
children should be able to carry on conversations using adult-like grammatical
forms and use sentences that provide details (e.g., “I like to read my books”).

Variations of Normal
Language milestones have been found to be largely universal across languages
and cultures, with some variations depending on the complexity of the
grammatical structure of individual languages. In Italian (where verbs often
occupy a prominent position at the beginning or end of sentences), 14 mo olds
produce a greater proportion of verbs compared with English speaking infants.
Within a given language, development usually follows a predictable pattern,
paralleling general cognitive development. Although the sequences are
predictable, the exact timing of achievement is not. There are marked variations
among normal children in the rate of development of babbling, comprehension
of words, production of single words, and use of combinational forms within the
first 2-3 yr of life.
Two basic patterns of language learning have been identified, analytic and
holistic. The analytic pattern is the most common and reflects the mastery of
increasingly larger units of language form. The child's analytic skills proceed
from simple to more complex and lengthy forms. Children who follow a holistic
or gestalt learning pattern might start by using relatively large chunks of speech
in familiar contexts. They might memorize familiar phrases or dialog from
movies or stories and repeat them in an overgeneralized fashion. Their sentences
often have a formulaic pattern, reflecting inadequate mastery of the use of
grammar to flexibly and spontaneously combine words appropriately in the
child's own unique utterance. Over time, these children gradually break down the
meanings of phrases and sentences into their component parts, and they learn to
analyze the linguistic units of these memorized forms. As this occurs, more
original speech productions emerge, and the child is able to assemble thoughts in
a more flexible manner. Both analytic and holistic learning processes are
necessary for normal language development to occur.

Language and Communication Disorders

Epidemiology
Disorders of speech and language are very common in preschool-age children.
Almost 20% of 2 yr olds are thought to have delayed onset of language. By age
5 yr, approximately 6% of children are identified as having a speech impairment,
5% as having both speech and language impairment, and 8% as having language
impairment. Boys are nearly twice as likely to have an identified speech or
language impairment as girls.

Etiology
Normal language ability is a complex function that is widely distributed across
the brain through interconnected neural networks that are synchronized for
specific activities. Although clinical similarities exist between acquired aphasia
in adults and childhood language disorders, unilateral focal lesions acquired in
early life do not seem to have the same effects in children as in adults. Risk
factors for neurologic injury are absent in the vast majority of children with
language impairment.
Genetic factors appear to play a major role in influencing how children learn
to talk. Language disorders cluster in families. A careful family history may
identify current or past speech or language problems in up to 30% of first-degree
relatives of proband children. Although children exposed to parents with
language difficulty might be expected to experience poor language stimulation
and inappropriate language modeling, studies of twins have shown the
concordance rate for low language test score and/or a history of speech therapy
to be approximately 50% in dizygotic pairs, rising to over 90% in monozygotic
pairs. Despite strong evidence that language disorders have a genetic basis,
consistent genetic mutations have not been identified. Instead, multiple genetic
regions and epigenetic changes may result in heterogeneous genetic pathways
causing language disorders. Some of these genetic pathways disrupt the timing
of early prenatal neurodevelopmental events affecting migration of nerve cells
from the germinal matrix to the cerebral cortex. Several single nucleotide
polymorphisms (SNPs) involving noncoding regulatory genes, including
CNTNAP2 (contactin-associated-protein-like-2) and KIAA0319 , are strongly
associated with early language acquisition and are also believed to affect early
neuronal structural development.
In addition, other environmental, hormonal, and nutritional factors may exert
epigenetic influences by dysregulating gene expression and resulting in aberrant
sequencing of the onset, growth, and timing of language development .

Pathogenesis
Language disorders are associated with a fundamental deficit in the brain's
capacity to process complex information rapidly. Simultaneous evaluation of
words (semantics), sentences (syntax), prosody (tone of voice), and social cues
can overtax the child's ability to comprehend and respond appropriately in a
verbal setting. Limitations in the amount of information that can be stored in
verbal working memory can further limit the rate at which language information
is processed. Electrophysiologic studies show abnormal latency in the early
phase of auditory processing in children with language disorders. Neuroimaging
studies identify an array of anatomic abnormalities in regions of the brain that
are central to language processing. MRI scans in children with specific language
impairment (SLI) may reveal white matter lesions and volume loss, ventricular
enlargement, focal gray matter heterotopia within the right and left
parietotemporal white matter, abnormal morphology of the inferior frontal gyrus,
atypical patterns of asymmetry of language cortex, or increased thickness of the
corpus callosum in a minority of affected children. Postmortem studies of
children with language disorders found evidence of atypical symmetry in the
plana temporale and cortical dysplasia in the region of the sylvian fissure. In
support of a genetic mechanism affecting cerebral development, a high rate of
atypical perisylvian asymmetries has also been documented in the parents of
children with SLI.

Clinical Manifestations
Primary disorders of speech and language development are often found in the
absence of more generalized cognitive or motor dysfunction. However, disorders
of communication are also the most common comorbidities in persons with
generalized cognitive disorders (intellectual disability or autism), structural
anomalies of the organs of speech (e.g., velopharyngeal insufficiency from cleft
palate), and neuromotor conditions affecting oral motor coordination (e.g.,
dysarthria from cerebral palsy or other neuromuscular disorders).

Classification
Each professional discipline has adopted a somewhat different classification
system, based on cluster patterns of symptoms. The American Psychiatric
Association (APA) Diagnostic and Statistical Manual of Mental Disorders, Fifth
Edition (DSM-5) organized communication disorders into: (1) language disorder
(which combines expressive and mixed receptive-expressive language
disorders), speech sound disorder (phonologic disorder), and childhood-onset
fluency disorder (stuttering); and (2) social (pragmatic) communication disorder,
which is characterized by persistent difficulties in the social uses of verbal and
nonverbal communication (Table 52.2 ). In clinical practice, childhood speech
and language disorders occur as a number of distinct entities.
Table 52.2
DSM-5 Diagnostic Criteria for
Communication Disorders
Language Disorder

A Persistent difficulties in the acquisition and use of language across

modalities (i.e., spoken, written, sign language, or other) due to deficits in
comprehension or production that include the following:
1. Reduced vocabulary (word knowledge and use).
2. Limited sentence structure (ability to put words and word endings
together to form sentences based on the rules of grammar and
morphology).
3. Impairments in discourse (ability to use vocabulary and connect
sentences to explain or describe a topic or series of events or have
a conversation).
B. Language abilities are substantially and quantifiably below those expected
for age, resulting in functional limitations in effective communication,
social participation, academic achievement, or occupational performance,
individually or in any combination.
C. Onset of symptoms is in the early developmental period.
D. The difficulties are not attributable to hearing or other sensory impairment,
 motor dysfunction, or another medical or neurologic condition and are not
better explained by intellectual disability (intellectual developmental
disorder) or global developmental delay.

Speech Sound Disorder

A. Persistent difficulty with speech sound production that interferes with

speech intelligibility or prevents verbal communication of messages.
B. The disturbance causes limitations in effective communication that
interfere with social participation, academic achievement, or occupational
performance, individually or in any combination.
C. Onset of symptoms is in the early developmental period.
D. The difficulties are not attributable to congenital or acquired conditions,
such as cerebral palsy, cleft palate, deafness or hearing loss, traumatic brain
injury, or other medical or neurologic conditions.

Social (Pragmatic) Communication Disorder

A. Persistent difficulties in the social use of verbal and nonverbal

communication as manifested by all of the following:
1. Deficits in using communication for social purposes, such as
greeting and sharing information, in a manner that is appropriate
for the social context.
2. Impairment of the ability to change communication to match
context or the needs of the listener, such as speaking differently
in a classroom than on a playground, talking differently to a child
than to an adult, and avoiding use of overly formal language.
3. Difficulties following rules for conversation and storytelling, such
as taking turns in conversation, rephrasing when misunderstood,
and knowing how to use verbal and nonverbal signals to regulate
interaction.
4. Difficulties understanding what is not explicitly stated (e.g.,
making inferences) and nonliteral or ambiguous meanings of
language (e.g., idioms, humor, metaphors, multiple meanings that
depend on the context for interpretation).
B. The deficits result in functional limitations in effective communication,
 social participation, social relationships, academic achievement, or
occupational performance, individually or in combination.
C. The onset of the symptoms is in the early developmental period (but
deficits may not become fully manifest until social communication
demands exceed limited capacities).
D. The symptoms are not attributable to another medical or neurologic
condition or to low abilities in the domains of word structure and grammar,
and are not better explained by autism spectrum disorder, intellectual
disability (intellectual developmental disorder), global developmental
delay, or another mental disorder.

From the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition,
(Copyright 2013). American Psychiatric Association, pp 42, 44, 47–48.

Language Disorder or Specific Language Impairment

The condition DSM-5 refers to as language disorder is also referred to as
specific language impairment (SLI) , developmental dysphasia , or
developmental language disorder . SLI is characterized by a significant
discrepancy between the child's overall cognitive level (typically nonverbal
measures of intelligence) and functional language level. These children also
follow an atypical pattern of language acquisition and use. Closer examination of
the child's skills might reveal deficits in understanding and use of word meaning
(semantics) and grammar (syntax). Often, children are delayed in starting to talk.
Most significantly, they usually have difficulty understanding spoken language.
The problem may stem from insufficient understanding of single words or from
the inability to deconstruct and analyze the meaning of sentences. Many affected
children show a holistic pattern of language development, repeating memorized
phrases or dialog from movies or stories (echolalia). In contrast to their difficulty
with spoken language, children with SLI appear to learn visually and
demonstrate their ability on nonverbal tests of intelligence.
After children with SLI become fluent talkers, they are generally less
proficient at producing oral narratives than their peers. Their stories tend to be
shorter and include fewer propositions, main story ideas, or story grammar
elements. Older children include fewer mental state descriptions (e.g., references
to what their characters think and how they feel). Their narratives contain fewer
cohesive devices, and the story line may be difficult to follow.
 Many children with SLI show difficulties with social interaction, particularly
with same-age peers. Social interaction is mediated by oral communication, and
a child deficient in communication is at a distinct disadvantage in the social
arena. Children with SLI tend to be more dependent on older children or adults,
who can adapt their communication to match the child's level of function.
Generally, social interaction skills are more closely correlated with language
level than with nonverbal cognitive level. Using this as a guide, one usually sees
a developmental progression of increasingly more sophisticated social
interaction as the child's language abilities improve. In this context, social
ineptitude is not necessarily a sign of asocial distancing (e.g., autism) but rather
a delay in the ability to negotiate social interactions.

Higher-Level Language Disorder

As children mature, the ability to communicate effectively with others depends
on mastery of a range of skills that go beyond basic understanding of words and
rules of grammar. Higher-level language skills include the development of
advanced vocabulary, the understanding of word relationships, reasoning skills
(including drawing correct inferences and conclusions), the ability to understand
things from another person's perspective, and the ability to paraphrase and
rephrase with ease. In addition, higher-order language abilities include pragmatic
skills that serve as the foundation for social interactions. These skills include
knowledge and understanding of one's conversational partner, knowledge of the
social context in which the conversation is taking place, and general knowledge
of the world. Social and linguistic aspects of communication are often difficult to
separate, and persons who have trouble interpreting these relatively abstract
aspects of communication typically experience difficulty forming and
maintaining relationships.
DSM-5 identified social (pragmatic) communication disorder (SPCD) as a
category of communication disorder (Table 52.2 ). Symptoms of pragmatic
difficulty include extreme literalness and inappropriate verbal and social
interactions. Proper use and understanding of humor, slang, and sarcasm depend
on correct interpretation of the meaning and the context of language and the
ability to draw proper inferences. Failure to provide a sufficient referential base
to one's conversational partner—to take the perspective of another person—
results in the appearance of talking or behaving randomly or incoherently. SPCD
often occurs in the context of another language disorder and has been recognized
as a symptom of a wide range of disorders, including right-hemisphere damage
to the brain, Williams syndrome, and nonverbal learning disabilities. SPCD can
also occur independently of other disorders. Children with autism spectrum
disorder (ASD) often have symptoms of SPCD, but SPCD is not diagnosed in
these children because the symptoms are a component of ASD. In school
settings, children with SPCD may be socially ostracized and bullied.

Intellectual Disability
Most children with a mild degree of intellectual disability learn to talk at a
slower-than-normal rate; they follow a normal sequence of language acquisition
and eventually master basic communication skills. Difficulties may be
encountered with higher-level language concepts and use. Persons with moderate
to severe degrees of intellectual disability can have great difficulty in acquiring
basic communication skills. About half of persons with an intelligence quotient
(IQ) of <50 can communicate using single words or simple phrases; the rest are
typically nonverbal.

Autism Spectrum Disorder

A disordered pattern of language development is one of the core features of ASD
(see Chapter 54 ). The language profile of children with ASD is often
indistinguishable from that in children with SLI or SPCD. The key
characteristics of ASD that distinguish it from SLI or SPCD are lack of
reciprocal social relationships; limitation in the ability to develop functional,
symbolic, or pretend play; hyper- or hyporeactivity to sensory input; and an
obsessive need for sameness and resistance to change. Approximately 40% of
children with ASD also have intellectual disability, which can limit their ability
to develop functional communication skills. Language abilities can range from
absent to grammatically intact, but with limited pragmatic features and odd
prosody patterns. Some individuals with ASD have highly specialized, but
isolated, “savant” skills, such as calendar calculations and hyperlexia (the
precocious ability to recognize written words beyond expectation based on
general intellectual ability). Parents report regression in language and social
skills (autistic regression ) in approximately 20–25% of children with ASD,
usually between 12 and 36 mo of age. The cause of the regression is not known,
but it tends to be associated with an increased risk for comorbid intellectual
disability and more severe ASD (Fig. 52.1 ).
 FIG. 52.1 Relationship of autism, language disorders, and intellectual
disability. (From Simms MD, Schum RL: Preschool children who have
atypical patterns of development, Pediatr Rev 21:147–158, 2000.)

Asperger Syndrome
Asperger syndrome is characterized by difficulties in social interaction,
eccentric behaviors, and abnormally intense and circumscribed interests despite
normal cognitive and verbal ability. Affected individuals may engage in long-
winded, verbose monologs about their topics of special interest, with little regard
to the reaction of others. Adults with Asperger syndrome generally have a more
favorable prognosis of than those with “classic” autism. Prior to 2013, Asperger
syndrome was classified as distinct from autism; however, DSM-5 no longer
recognizes Asperger as a separate neurodevelopmental disorder. More severely
affected individuals are now considered to be at the “high functioning” end of
the autism spectrum (see Chapter 54 ), whereas mildly impaired individuals may
be diagnosed with SPCD.

Selective Mutism
Selective mutism is defined as a failure to speak in specific social situations
despite speaking in other situations, and it is typically a symptom of an
underlying anxiety disorder . Children with selective mutism can speak
normally in certain settings, such as within their home or when they are alone
with their parents. They fail to speak in other social settings, such as at school or
at other places outside their home. Other symptoms associated with selective
mutism can include excessive shyness, withdrawal, dependency on parents, and
oppositional behavior. Most cases of selective mutism are not the result of a
single traumatic event, but rather the manifestation of a chronic pattern of
anxiety. Mutism is not passive-aggressive behavior. Selectively mute children
often report that they want to speak in social settings but are afraid to do so.
Often, one or both parents of a child with selective mutism has a history of
anxiety symptoms, including childhood shyness, social anxiety, or panic attacks.
Mutism is highly functional for the child in that it reduces anxiety and protects
the child from the perceived challenge of social interaction. Treatment of
selective mutism should utilize cognitive behavioral strategies focused on
reducing the general anxiety and increasing speaking in social situation (see
Chapter 38 ). Occasionally, selective serotonin reuptake inhibitors are helpful in
conjunction with cognitive-behavioral therapy. Selective mutism reflects a
difficulty of social interaction, not a disorder of language processing.

Isolated Expressive Language Disorder

More often seen in boys than girls, isolated expressive language disorder (“late
talker syndrome”) is a diagnosis best made in retrospect. These children have
age-appropriate receptive language and social ability. Once they start talking,
their speech is clear. There is no increased risk for language or learning disability
as they progress through school. A family history of other males with a similar
developmental pattern is often reported. This pattern of language development
likely reflects a variation of normal.

Motor Speech Disorders

Dysarthria
Motor speech disorders can originate from neuromotor disorders such as cerebral
palsy, muscular dystrophy, myopathy, and facial palsy. The resulting dysarthria
affects both speech and nonspeech functions (smiling and chewing). Lack of
strength and muscular control manifests as slurring of words and distorting of
vowels. Speech patterns are often slow and labored. Poor velopharyngeal
function can result in mixed nasal resonance (hyper- or hyponasal speech). In
many cases, feeding difficulty, drooling, open-mouth posture, and protruding
tongue accompany the dysarthric speech.

Childhood Apraxia of Speech

Difficulty in planning and coordinating movements for speech production can
result in inconsistent distortion of speech sounds. The same word may be
pronounced differently each time. Intelligibility tends to decline as the length
and complexity of the child's speech increases. Consonants may be deleted and
sounds transposed. As they try to talk spontaneously, or imitate other's speech,
children with childhood apraxia of speech may display oral groping or
struggling behaviors. Children with childhood apraxia of speech frequently have
a history of early feeding difficulty, limited sound production as infants, and
delayed onset of spoken words. They may point, grunt, or develop an elaborate
gestural communication system in an attempt to overcome their verbal difficulty.
Apraxia may be limited to oral-motor function, or it may be a more generalized
problem affecting fine and/or gross motor coordination.

Speech Sound Disorder

Children with speech sound disorder (SSD) , previously called phonologic
disorder, are often unintelligible, even to their parents. Articulation errors are not
the result of neuromotor impairment, but rather seem to reflect an inability to
correctly process the words they hear (Table 52.2 ). As a result, they lack
understanding of how to fit sounds together properly to create words. In contrast
to children with childhood apraxia of speech, those SSD are fluent, although
unintelligible, and produce a consistent, highly predictable pattern of articulation
errors. Children with SSD are at high risk for later reading and learning
disability.

Hearing Impairment
Hearing loss can be a major cause of delayed or disordered language
development (see Chapter 655 ). Approximately 16-30 per 1,000 children have
mild to severe hearing loss, significant enough to affect educational progress. In
addition to these “hard of hearing” children, approximately another 1 : 1,000 are
deaf (profound bilateral hearing loss). Hearing loss can be present at birth or
acquired postnatally. Newborn screening programs can identify many forms of
congenital hearing loss, but children can develop progressive hearing loss or
acquire deafness after birth.
The most common types of hearing loss are attributable to conductive (middle
ear) or sensorineural deficit. Although it is not possible to accurately predict the
impact of hearing loss on a child's language development, the type and degree of
hearing loss, the age of onset, and the duration of the auditory impairment
clearly play important roles. Children with significant hearing impairment often
have problems developing facility with language and often have related
academic difficulties. Presumably, the language impairment is caused by lack of
exposure to fluent language models, starting in infancy.
Approximately 30% of hearing-impaired children have at least 1 other
disability that affects development of speech and language (e.g., intellectual
disability, cerebral palsy, craniofacial anomalies). Any child who shows
developmental warning signs of a speech or language problem should have a
hearing assessment by an audiologist.

Hydrocephalus
Some children with hydrocephalus may be described as having “cocktail-party
syndrome.” Although they may use sophisticated words, their comprehension of
abstract concepts is limited, and their pragmatic conversational skills are weak.
As a result, they speak superficially about topics and appear to be carrying on a
monolog (see Chapter 609.11 ).

Rare Causes of Language Impairment

Hyperlexia
Hyperlexia is the precocious development of reading single words that
spontaneously occurs in some young children (2-5 yr) without specific
instruction. It is often associated with ASD or SLI. It stands in contrast to
precocious reading development in young children who do not have any other
developmental disorders. A typical manifestation is a child with SLI orally
reading single words or matching pictures with single words. Although
hyperlexic children show early and well-developed word-decoding skills, they
usually do not have precocious ability for comprehension of text. Rather, text
comprehension is closely intertwined with oral comprehension, and children
who have difficulty decoding the syntax of language are also at risk for having
reading comprehension problems.
Landau-Kleffner Syndrome (Verbal Auditory
Agnosia)
Children with Landau-Kleffner syndrome have a history of normal language
development until they experience a regression in their ability to comprehend
spoken language, verbal auditory agnosia . The regression may be sudden or
gradual, and it usually occurs between 3 and 7 yr of age. Expressive language
skills typically deteriorate, and some children may become mute. Despite their
language regression, these children typically retain appropriate play patterns and
the ability to interact in a socially appropriate manner. An electroencephalogram
(EEG) might show a distinct pattern of status epilepticus in sleep (continuous
spike wave in slow-wave sleep), and up to 80% of children with Landau-
Kleffner syndrome eventually exhibit clinical seizures. A number of treatment
approaches have been reported, including antiepileptic medication,
corticosteroids, and intravenous gamma globulin, with varying results. The
prognosis for return of normal language ability is uncertain, even with resolution
of the EEG abnormality. Epileptic interictal discharges are more frequently
found on EEGs of children with language impairments than in otherwise
normally developing children, even in those without any history of language
regression. However, this phenomenon is believed to represent a manifestation
of an underlying disorder of brain structure or function that is distinct from the
language impairment, because there has been little evidence of improvement in
language function when the EEG was normalized after antiepileptic
administration. Unless there is a clear pattern of either seizure symptoms or
regression in language ability, a routine EEG is not recommended as part of the
evaluation for a child with speech and/or language impairment.

Metabolic and Neurodegenerative Disorders

(See also Part X.)
Regression of language development may accompany loss of neuromotor
function at the outset of a number of metabolic diseases, including lysosomal
storage disorders (metachromatic leukodystrophy), peroxisomal disorders
(adrenal leukodystrophy), ceroid lipofuscinosis (Batten disease), and
mucopolysaccharidosis (Hunter disease, Hurler disease). Recently, creatine
transporter deficiency was identified as an X-linked disorder that manifests with
language delay in boys and with mild learning disability in female carriers.
Screening
Developmental surveillance at each well child visit should include specific
questions about normal language developmental milestones and observations of
the child's behavior. Clinical judgment, defined as eliciting and responding to
parents' concerns, can detect the majority of children with speech and language
problems. The AAP recommends clinicians employ standardized developmental
screening questionnaires and observation checklists at select well child visits.
(see Chapter 28 ).
In 2015 the U.S. Preventive Services Task Force reviewed screening for SLI
in young children in primary care settings and found inadequate evidence to
support screening in the absence of parental or clinician concern about children's
speech, language, hearing, or development. When either parents or physicians
are concerned about speech or language development for reasons such as
highlighted in Table 52.3 , the child should be referred for further evaluation and
intervention (see Diagnostic Evaluation ).

Table 52.3
Speech and Language Screening
REFER FOR SPEECH–LANGUAGE EVALUATION IF:
AT RECEPTIVE EXPRESSIVE
AGE
15 Does not look/point at 5-10 objects Is not using 3 words
mo
18 Does not follow simple directions (“get Is not using Mama, Dada, or other names
mo your shoes”)
24 Does not point to pictures or body parts Is not using 25 words
mo when they are named
30 Does not verbally respond or nod/shake Is not using unique 2-word phrases, including noun–verb
mo head to questions combinations
36 Does not understand prepositions or Has a vocabulary of <200 words; does not ask for things;
mo action words; does not follow 2-step echolalia to questions; language regression after attaining 2-
directions word phrases

Noncauses of Language Delay

Twinning, birth order, “laziness,” exposure to multiple languages (bilingualism),
tongue-tie (ankyloglossia), or otitis media are not adequate explanations for
significant language delay. Normal twins learn to talk at the same age as normal
single-born children, and birth-order effects on language development have not
been consistently found. The drive to communicate and the rewards for
successful verbal interaction are so strong that children who let others talk for
them usually cannot talk for themselves and are not “lazy.” Toddlers exposed to
more than one language can show a mild delay in starting to talk, and they can
initially mix elements (vocabulary and syntax) of the different languages they
are learning (code switching). However, they learn to segregate each language
by 24-30 mo and are equal to their monolingual peers by 3 yr of age. An
extremely tight lingual frenulum (tongue-tie) can affect feeding and speech
articulation but does not prevent the acquisition of language abilities.
Prospective studies also show that frequent ear infections and serous otitis media
in early childhood do not result in persisting language disorder.

Diagnostic Evaluation
It is important to distinguish developmental delay (abnormal timing) from
abnormal patterns or sequences of development. A child's language and
communication skills must also be interpreted within the context of the child's
overall cognitive and physical abilities. It is also important to evaluate the child's
use of language to communicate with others in the broadest sense
(communicative intent). Thus a multidisciplinary evaluation is often warranted.
At a minimum, this should include psychologic evaluation, neurodevelopmental
pediatric assessment, and speech-language examination.

Psychologic Evaluation
There are two main goals for the psychologic evaluation of a young child with a
communication disorder. Nonverbal cognitive ability must be assessed to
determine if the child has an intellectually disability, and the child's social
behaviors must be assessed to determine whether ASD is present. Additional
diagnostic considerations may include emotional disorders such as anxiety,
depression, mood disorder, obsessive-compulsive disorder, academic learning
disorders, and attention-deficit/hyperactivity disorder (ADHD).

Cognitive Assessment
Intellectual disability is defined as deficits in cognitive abilities and adaptive
behaviors. In this context, children with intellectual disability show delayed
development of communication skills; however, delayed communication does
not necessarily signal intellectual disability. Therefore, a broad-based cognitive
assessment is an important component to the evaluation of children with
language delays, including evaluation of both verbal and nonverbal skills. If a
child has intellectual disability, both verbal and nonverbal scores will be low
compared to norms (≤2nd percentile). In contrast, a typical cognitive profile for
a child with SLI includes a significant difference between nonverbal and verbal
abilities, with nonverbal IQ being greater than verbal IQ and the nonverbal score
being within an average range.

Evaluation of Social Behaviors

Social interest is the key difference between children with a primary language
disorder (SLI) and those with a communication disorder secondary to ASD.
Children with SLI have an interest in social interaction, but they may have
difficulty enacting their interest because of their limitations in communication.
In contrast, autistic children show little social interest.

Relationship of Language and Social Behaviors to Mental

Age
Cognitive assessment provides a mental age for the child, and the child's
behavior must be evaluated in that context. Most 4 yr old children typically
engage peers in interactive play, but most 2 yr olds are playful but primarily
focused on interactions with adult caretakers. A 4 yr old with mild to moderate
intellectual disability and a mental age of 2 yr might not yet play with peers
because of cognitive limitation, not a lack of desire for social interaction.

Speech and Language Evaluation

A certified speech-language pathologist should perform a speech and language
evaluation. A typical evaluation includes assessment of language, speech, and
the physical mechanisms associated with speech production. Both expressive
and receptive language is assessed by a combination of standardized measures
and informal interactions and observations. All components of language are
assessed, including syntax, semantics, pragmatics, and fluency. Speech
assessment similarly uses a combination of standardized measures and informal
observations. Assessment of physical structures includes oral structures and
function, respiratory function, and vocal quality. In many settings, a speech-
language pathologist works in conjunction with an audiologist, who can do
appropriate hearing evaluation of the child. If an audiologist is not available in
that setting, a separate referral should be made. No child is too young for a
speech-language or hearing evaluation. A referral for evaluation is appropriate
whenever there is suspicion of language impairment.

Medical Evaluation
Careful history and physical examination should focus on the identification of
potential contributors to the child's language and communication difficulties. A
family history of delay in talking, need for speech and language therapy, or
academic difficulty can suggest a genetic predisposition to language disorders.
Pregnancy history might reveal risk factors for prenatal developmental
anomalies, such as polyhydramnios or decreased fetal movement patterns. Small
size for gestational age at birth, symptoms of neonatal encephalopathy, or early
and persistent oral-motor feeding difficulty may presage speech and language
difficulty. Developmental history should focus on the age when various
language skills were mastered and the sequences and patterns of milestone
acquisition. Regression or loss of acquired skills should raise immediate
concern.
Physical examination should include measurement of height (length), weight,
and head circumference. The skin should be examined for lesions consistent with
phakomatosis (e.g., tuberous sclerosis, neurofibromatosis, Sturge-Weber
syndrome) and other disruptions of pigment (e.g., hypomelanosis of Ito).
Anomalies of the head and neck, such as white forelock and hypertelorism
(Waardenburg syndrome), ear malformations (Goldenhar syndrome), facial and
cardiac anomalies (Williams syndrome, velocardiofacial syndrome),
retrognathism of the chin (Pierre Robin anomaly), or cleft lip/palate, are
associated with hearing and speech abnormalities. Neurologic examination
might reveal muscular hypertonia or hypotonia, both of which can affect
neuromuscular control of speech. Generalized muscular hypotonia, with
increased range of motion of the joints, is frequently seen in children with SLI.
The reason for this association is not clear, but it might account for the fine and
gross motor clumsiness often seen in these children. However, mild hypotonia is
not a sufficient explanation for the impairment of expressive and receptive
language.
No routine diagnostic studies are indicated for SLI or isolated language
disorders. When language delay is a part of a generalized cognitive or physical
disorder, referral for further genetic evaluation, chromosome testing (e.g., fragile
X testing, microarray comparative genomic hybridization), neuroimaging
studies, and EEG may be considered, if clinically indicated.

Treatment
The federal Individuals with Disabilities Education Act (IDEA) requires that
schools provide early intervention and special education services to children
who have learning difficulties. This includes children with speech and language
disorders. Services are provided to children from birth through 21 yr of age.
States have various methods for providing services, including speech and
language therapy for young children, such as Birth-to-Three , Early Childhood ,
and Early Learning programs. Children can also receive therapy from nonprofit
service agencies, hospital and rehabilitation centers, and speech pathologists in
private practice.
Of concern is that many children with identified speech and language deficits
do not receive appropriate intervention services. Population-based surveys in
both the United States and Canada have found that less than half of children
identified by kindergarten entry receive speech and language interventions ,
even when their parents have been educated about the nature of their child's
condition. In one study, children with deficits in speech sound production were
much more likely to receive services (41%) than those who had problems with
language alone (9%). These findings are troubling because poor educational
outcome, especially in reading, and impaired social-behavioral adjustment are
more highly associated with language than with speech sound disorders.
Therefore the children at greatest risk are least likely to receive intervention
services. Boys were twice as likely to receive speech intervention as girls,
regardless of their speech-language diagnosis. Social and demographic factors
did not appear to influence whether identified children received interventions
services.
Speech-language therapy includes a variety of goals. Sometimes both speech
and language activities are incorporated in therapy. The speech goals focus on
development of more intelligible speech. Language goals can focus on
expanding vocabulary (lexicon) and understanding of the meaning of words
(semantics), improving syntax by using proper forms or learning to expand
single words into sentences, and social use of language (pragmatics). Therapy
can include individual sessions, group sessions, and mainstream classroom
integration. Individual sessions may use drill activities for older children or play
activities for younger children to target specific goals. Group sessions can
include several children with similar language goals to help them practice peer
communication activities and to help them bridge the gap into more naturalistic
communication situations. Classroom integration might include the therapist
team-teaching or consulting with the teacher to facilitate the child's use of
language in common academic situations.
For children with severe language impairment, alternative methods of
communication are often included in therapy, such as manual sign language, use
of pictures (e.g., Picture Exchange Communication System), and computerized
devices for speech output. Often the ultimate goal is to achieve better spoken
language. Early use of signs or pictures can help the child establish better
functional communication and understand the symbolic nature of words to
facilitate the language process. There is no evidence that use of signs or pictures
interferes with development of oral language if the child has the capacity to
speak. Many clinicians believe that these alternative methods accelerate the
learning of language. These methods also reduce the frustration of parents and
children who cannot communicate for basic needs.
Parents can consult with their child's speech-language therapist about home
activities to enhance language development and extend therapy activities
through appropriate language-stimulating activities and recreational reading.
Parents' language activities should focus on emerging communication skills that
are within the child's repertoire, rather than teaching the child new skills. The
speech pathologist can guide parents on effective modeling and eliciting
communication from their child.
Recreational reading focuses on expanding the child's comprehension of
language. Sometimes the child's avoidance of reading is a sign that the parent is
presenting material that is too complex for the child. The speech-language
therapist can guide the parent in selecting an appropriate level of reading
material.

Prognosis
Children with mild isolated expressive language disorder (“late talkers”) have an
excellent prognosis for both language, learning, and social-emotional
adjustment.
 Over time, children with SLI respond to therapeutic/educational interventions
and show a trend toward improvement of communication skills. Adults with a
history of childhood language disorder continue to show evidence of impaired
language ability, even when surface features of the communication difficulty
have improved considerably. This suggests that many persons find successful
ways of adapting to their impairment. Although the majority of children improve
their communication ability with time, 50–80% of preschoolers with language
delay and normal nonverbal intelligence continue to experience difficulty with
language and social development up to 20 yr beyond the initial diagnosis.
Language disorders often interfere with the child's ability to conceptualize the
increasingly complex and ambiguous worlds of social relationship and emotions.
Consequently, in later childhood and adolescence, children with persisting
symptoms of SLI are about twice as likely as their typical-language peers to
show clinical levels of emotional problems and twice as likely to show
behavioral difficulties.
A Danish study found that adults with SLI were less likely to have completed
formal education beyond high school, and that they had lower occupational and
socioeconomic success than the general population; 56% had a paid job (vs 84%
of same-age general population), of whom 35% were unskilled and 40% skilled
workers. About 80% of the adults reported difficulty reading while in school,
most had received remedial teaching, and 50% continued to report reading
difficulty as adults (vs 5% of Danish adults). Lower nonverbal intelligence and
comorbid psychiatric or neurologic disorders independently contributed to a
worse prognosis. These results were consistent with previous reports of adult
outcomes of children with SLI from Canada and the United Kingdom.

Academic Disorders
Early language difficulty is strongly related to later reading disorder .
Approximately 50% of children with early language difficulty develop reading
disorder, and 55% of children with reading disorder have a history of impaired
early oral language development. By the time they enter kindergarten, many
children with early language deficits may have improved significantly, and they
may begin to show early literacy skills, identifying and sounding out letters.
However, as they progress through school, they are often unable to keep up with
the increasing demands for both oral and written language. Despite their ability
to read words, these children lack oral and reading comprehension, may read
slowly, and struggle with a wide range of academic subjects. This “illusory
recovery” of early language skill may result in children losing speech-language
services or other special education support in early grades, only to be identified
later with academic problems. In addition, children with subtle but persisting
language impairments may appear inattentive or anxious in language-rich
classroom environments and may be misdiagnosed as having an attention
disorder.
A study from Australia found that at 7-9 yr of age, children with
communication impairments were reported by their parents and teachers to be
making slower progress in reading, writing, and overall school achievement than
other children their age. The children reported a higher incidence of bullying,
poorer peer relationships, and less overall enjoyment of school than their
typically developing peers.

Comorbid Disorders
Emotional and Behavioral Difficulty
Early language disorder, particularly difficulty with auditory comprehension,
appears to be a specific risk factor for later emotional dysfunction. Boys and
girls with language disorder have a higher-than-expected rate of anxiety
disorder (principally social phobia). Boys with language disorder are more
likely to develop symptoms of ADHD, conduct disorder, and antisocial
personality disorder compared with normally developing peers. Language
disorders are common in children referred for psychiatric services, but they are
often underdiagnosed, and their impact on children's behavior and emotional
development is often overlooked.
Preschoolers with language difficulty frequently express their frustration
through anxious, socially withdrawn, or aggressive behavior. As their ability to
communicate improves, parallel improvements are usually noted in their
behavior, suggesting a cause-and-effect relationship between language and
behavior. However, the persistence of emotional and behavioral problems over
the life span of persons with early language disability suggests a strong biologic
or genetic connection between language development and subsequent emotional
disorders.
The full impact of environmental and education support on these emotional
and behavioral difficulties is not known at this time, but many children with SLI
need psychologic support. Efforts should be made to support the child's
resilience, emotional competency, and coping abilities. Parents and teachers
should be encouraged to strengthen the child's prosocial behavior and reduce
noncompliant and aggressive behaviors.

Motor and Coordination Delays

Approximately one third to one half of children with speech and/or language
disorders have some degree of motor coordination impairment that may have an
important impact on their ability to carry out activities of daily living (dressing,
eating, bathing), school tasks (writing, drawing, coloring), and
social/recreational activities (participation in sports and other playground
activities). Motor difficulties are not related to the type of language impairment
(i.e., they are found both in children with only receptive delays and in those with
both expressive and receptive delays). The patterns of motor difficulty seen in
children with language impairment are not distinctly “abnormal,” and the motor
profiles of children with language impairment resemble those of younger
children, suggesting that they result from delayed maturation of motor
development rather than from a neurologic impairment. Several researchers have
postulated that language impairments and motor difficulties may have a common
neurodevelopmental basis. Because attention may be focused on the child's
language delays, the need for intervention and support for the child's comorbid
motor impairment may be overlooked.

52.1
Childhood-Onset Fluency Disorder
Kenneth L. Grizzle

Keywords
 childhood-onset fluency disorder
cluttering
physical concomitants
stammering, stuttering

Developmental stuttering is a childhood speech disorder that is not associated

with stroke, traumatic brain injury, or other possible medical conditions and that
interrupts the normal flow of speech through repeated or prolonged sounds,
syllables, or single-syllable words. (Table 52.4 lists definitions of terminology.)
All speakers experience speech dysfluencies . During the toddler and preschool
years, children often make repetitions of sounds, syllables, or words, particularly
at the beginning of sentences (normal dysfluencies). However, dysfluencies
found in individuals who stutter are distinct from those experienced by typically
developing speakers. Specifically, children who stutter show greater part-word
repetition (“b-b-b-b-but”), single-syllable word repetition (“My, my, my”), and
sound prolongation (“MMMMMM-an”), and the frequency of their stuttering is
much greater than found in normal dysfluencies. Other types of dysfluency that
are not exclusive to children who stutter include interjections (“well, uhh,
umm”), revisions (“I thought…I mean”), and phrase repetitions (“Did you say–
Did you say”). The perspective of the speaker also characterizes differences
between those children who stutter and a typical dysfluency. Children who
stutter have decided on a word to use but are unable to “get the word out,” while
a typically developing child may struggle to express herself because she is
unable to retrieve the word, changes thought, or is distracted.

Table 52.4

Terminology Related to Childhood-Onset Fluency Disorder

TERM DEFINITION
Stuttering A speech disorder manifested through abnormal speech patterns referred to as
dysfluencies
Childhood-onset Term used in DSM-5 that is synonymous with stuttering
fluency disorder
Stammering The clinical term used in the United Kingdom rather than stuttering; stammering also
used informally to describe halting speech
Cluttering A speech disorder characterized by excessively rapid and irregular rate of speech
Dysfluency Speech disruptions that can occur in normal or disordered speech

Multiple nonspeech features can accompany stuttering. Physical

concomitants that occur at the onset and as the condition persists include
movements of the head (head turning or jerking), face (eye blinking/squinting,
grimacing, opening or tightly closing the jaw), and neck (tightening) and
irregular inhalations and exhalations. Fear and anxiety about speaking in a large-
group setting, such as in front of a class or in interpersonal social interactions,
are emotional symptoms associated with stuttering. As with all social beings,
children closely monitor the reactions of those with whom they associate,
especially as they get older. It is not difficult to imagine the impact a single or
series of negative interactions or comments could have on a child's future
attempts to interact verbally with another or in a large social setting. Consider
also the potential social challenges associated with entering a classroom for the
first time, transitioning to middle/high school/college, beginning a job, dating,
and so on. Not surprisingly, avoidance is a common way of coping with the
anxiety created by the fear of stuttering.
In the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition
(DSM-5), the term stuttering has been removed from the diagnostic
classification, and the disorder is referred to as childhood-onset fluency
disorder (Table 52.5 ). Note that impact on functional behavior is a component
of the psychiatric diagnosis of this condition. In contrast, communication
disorder specialists would consider possible anxiety and avoidance of various
activities and situations a common concomitant of childhood-onset fluency
disorder (stuttering) and not necessarily a requirement for the diagnosis to be
made.
Table 52.5
DSM-5 Diagnostic Criteria for Childhood-
Onset Fluency Disorder (Stuttering)

A. Disturbances in the normal fluency and time patterning of speech that are
inappropriate for the individual's age and language skills, persist over time,
and are characterized by frequent and marked occurrences of one (or more)
of the following:
1. Sound and syllable repetitions.
2. Sound prolongations of consonants as well as vowels.
3. Broken words (e.g., pauses within a word).
4. Audible or silent blocking (filled or unfilled pauses in speech).
5. Circumlocutions (word substitutions to avoid problematic words).
6. Words produced with an excess of physical tension.
 7. Monosyllabic whole-word repetitions (e.g., “I-I-I-I see him”).
B. The disturbance causes anxiety about speaking or limitations in effective
communication, social participation, or academic or occupational
performance, individually or in any combination.
C. The onset of symptoms is in the early developmental period.
Note: Later-onset cases are diagnosed as 307.0 [F98.5] adult-onset fluency
disorder.
D. The disturbance is not attributable to a speech-motor or sensory deficit,
dysfluency associated with neurologic insult (e.g., stroke, tumor, trauma),
or another medical condition and is not better explained by another mental
disorder.

From the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition,
(Copyright 2013). American Psychiatric Association, pp 45–46.)

Stuttering is distinct from other disordered speech output conditions such as

cluttering in several ways. Unlike stuttering, for which distinct episodes can be
identified and even counted, cluttering affects the entire speech output. In
addition to elevated repetitions of partial words (as in stuttering), whole words,
and phrases, those who clutter show speech bursts that are often choppy, and
articulation can be slurred and imprecise. The level of awareness of how their
speech affects those listening, unlike children who stutter, is minimal for those
who clutter. Stammering and stuttering are terms used interchangeably,
although the former is used in the United Kingdom and the latter in the United
States. “Stammer” is also used informally to describe when an individual is
struggling to express himself and may speak in a halting or “bumbling” manner.

Epidemiology
Although prevalence studies have produced a range of estimates for
developmental stuttering, it appears that 0.75–1% of the population is
experiencing this condition at any one time. Incidence rates are considerably
higher: Estimates to date suggest an incidence rate of approximately 5%, with
rates considerably higher among young children than older children or
adolescents. Seldom does a child begin stuttering before 2 yr of age or after 12
yr; in fact, the mean age of onset is 2-4 yr, and most children stop stuttering
within 4 yr of onset. Symptoms will disappear within 4 wk for a minority of
children. Although studies have consistently shown that the male:female ratio
favors males, the magnitude of the pattern increases as children get older. The
ratio among children <5 yr is approximately 2 : 1 and jumps to 4 : 1 among
adolescents and young adults.

Genetics
There is convergent evidence of a genetic link for childhood-onset fluency
disorder. Concordance rates among MZ twins range from 20–83%, and for DZ
twins, 4–19%. Family aggregation studies suggest increased incidence rate of
approximately 15% among first-degree relatives of those affected, 3 times higher
than the 5% rate for the general population. The variance in risk for stuttering
attributed to genetic effects is high, ranging from 70–85%. Although evidence is
limited, stuttering appears to be a polygenic condition, and several genes
increase susceptibility.

Etiology
Brain structure and function abnormalities found in stutterers include deficits in
white matter in the left hemisphere, overactivity in the right cortical region, and
underactivity in the auditory cortex. Abnormal basal ganglia activation has also
been identified among stutterers.

Comorbidities
Despite the widely held belief in a high degree of comorbidity between
childhood-onset fluency disorder and other communication disorders, research to
date does not necessarily support this assertion. Speech-language pathologists
(SLPs) consistently report higher rates of comorbidity on their caseload,
although this would be expected in clinical samples. Speech sound (phonologic)
disorders are the most commonly reported comorbidities, and 30–40% of
children on SLP caseloads are also experiencing problems with phonology.
However, studies have not found greater incidence of phonologic disorders
among those who stutter compared to a control group. Similarly, SLPs report a
much higher percentage of children with language disorders among their patients
who stutter than the approximately 7% expected in the population at large, yet
the language functioning among stutters apparently is no different than in the
general population. The same pattern holds for learning disorder (LD). The
incidence of various types of LDs associated with a language disorder is well
documented, so one would expect to see increased frequency within a clinical
population.
The perception of communication disorder professionals and people in general
is that children who stutter experience more anxiety than their nonstuttering
peers. This in fact is supported by clinical research that has found considerably
higher rates of psychopathology, specifically social anxiety and generalized
anxiety disorder, among adolescents who stutter. The frequency of reported
anxiety increases with age. To date, however, the lack of controlled studies
should not lead to the assumption that stuttering itself places a child or
adolescent at greater risk for a psychiatric disorder of any type. This is not meant
to suggest that anxiety has no impact on a stuttering child's behavior in specific
situations; as indicated earlier in this chapter, children who stutter frequently
avoid situations that demand speaking.
Children who stutter have consistently been found to be bullied more than
peers. In one study, stutterers were almost 4 times more likely to be bullied than
their nonstuttering counterparts. About 45% of those who stuttered reported
being the victim of bullying.

Developmental Progression
Onset of stuttering typically occurs between 2 and 4 yr of age. Severity of
symptoms vary, from pronounced stuttering within a few days of onset to
gradual worsening of symptoms across months. Symptoms may ebb and flow,
including disappearing for weeks before returning, especially among young
children. From 40–75% of young children who stutter will stop spontaneously,
typically within months of starting. Although predicting which child will stop
stuttering is difficult, risk factors for persisting include stuttering for >1 yr,
continued stuttering after age 6 yr, and experiencing other speech or language
problems.

Treatment
Several factors should be considered when deciding to refer a younger child with
childhood-onset fluency disorder for therapy. If there is a positive family history
for stuttering, if symptoms have been present for >4 wk, and if the dysfluencies
are impacting the child's social, behavioral, and emotional functioning, referral is
warranted. Although there is no cure for stuttering, behavioral therapies are
available that are developed and implemented by SLPs. Treatment emphasizes
managing stuttering while speaking by regulating rate of speech and breathing
and helping the child gradually progress from the fluent production of syllables
to more complex sentences. Approaches to treatment may include parents
directly in the process, although even if not active participants, parents play an
important role in the child coping with stuttering. Treatment in preschool-age
children has been shown to improve stuttering. Management of stuttering is also
emphasized in older children. For school-age children, treatment includes
improving not only fluency but also concomitants of the condition. This includes
recognizing and accepting stuttering and appreciating others' reaction to the child
when stuttering, managing secondary behaviors, and addressing avoidance
behaviors. The broad focus allows for minimizing the adverse effects of the
condition. To date, no evidence supports the use of a pharmacologic agent to
treat stuttering in children and adolescents.
Preschool children with normal developmental dysfluency can be observed
with parental education and reassurance. Parents should not reprimand the child
or create undue anxiety.
Preschool or older children with stuttering should be referred to a speech
pathologist. Therapy is most effective if started during the preschool period. In
addition to the risks noted in Table 52.5 , indications for referral include 3 or
more dysfluencies per 100 syllables (b-b-but; th-th-the; you, you, you),
avoidances or escapes (pauses, head nod, blinking), discomfort or anxiety while
speaking, and suspicion of an associated neurologic or psychotic disorder.
Most preschool children respond to interventions taught by speech
pathologists and to behavioral feedback by parents. Parents should not yell at the
child, but should calmly praise periods of fluency (“That was smooth”) or
nonjudgmentally note episodes of stuttering (“That was a bit bumpy”). The child
can be involved with self-correction and respond to requests (“Can you say that
again?”) made by a calm parent. Such treatment greatly improves dysfluency,
but it may never be eliminated.
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CHAPTER 53

Developmental Delay and Intellectual

Disability
Bruce K. Shapiro, Meghan E. O'Neill

Intellectual disability (ID) refers to a group of disorders that have in common

deficits of adaptive and intellectual function and an age of onset before maturity
is reached.

Definition
Contemporary conceptualizations of ID emphasize functioning and social
interaction rather than test scores. The definitions of ID by the World Health
Organization (WHO) International Classification of Diseases, Tenth Edition
(ICD-10), the U.S. Individuals with Disabilities Education Act (IDEA), the
American Psychiatric Association (APA) Diagnostic and Statistical Manual of
Mental Disorders, Fifth Edition (DSM-5), and the American Association on
Intellectual and Developmental Disabilities (AAIDD) all include significant
impairment in general intellectual function (reasoning, learning, problem
solving), social skills, and adaptive behavior. This focus on conceptual, social,
and practical skills enables the development of individual treatment plans
designed to enhance functioning. Consistent across these definitions is onset of
symptoms before age 18 yr or adulthood.
Significant impairment in general intellectual function refers to performance
on an individually administered test of intelligence that is approximately 2
standard deviations (SD) below the mean. Generally these tests provide a
standard score that has a mean of 100 and SD of 15, so that intelligence quotient
(IQ) scores <70 would meet these criteria. If the standard error of measurement
is considered, the upper limits of significantly impaired intellectual function may
extend to an IQ of 75. Using a score of 75 to delineate ID might double the
number of children with this diagnosis, but the requirement for impairment of
adaptive skills limits the false positives. Children with ID often show a variable
pattern of strengths and weaknesses. Not all their subtest scores on IQ tests fall
into the significantly impaired range.
Significant impairment in adaptive behavior reflects the degree that the
cognitive dysfunction impairs daily function. Adaptive behavior refers to the
skills required for people to function in their everyday lives. The AAIDD and
DSM-5 classifications of adaptive behavior addresses three broad sets of skills:
conceptual, social, and practical. Conceptual skills include language, reading,
writing, time, number concepts, and self-direction. Social skills include
interpersonal skills, personal and social responsibility, self-esteem, gullibility,
naiveté, and ability to follow rules, obey laws, and avoid victimization.
Representative practical skills are performance of activities of daily living
(dressing, feeding, toileting/bathing, mobility), instrumental activities of daily
living (e.g., housework, managing money, taking medication, shopping,
preparing meals, using phone), occupational skills, and maintenance of a safe
environment. For a deficit in adaptive behavior to be present, a significant delay
in at least 1 of the 3 skill areas must be present. The rationale for requiring only
1 area is the empirically derived finding that people with ID can have varying
patterns of ability and may not have deficits in all 3 areas.
The requirement for adaptive behavior deficits is the most controversial aspect
of the diagnostic formulation. The controversy centers on two broad areas:
whether impairments in adaptive behavior are necessary for the construct of ID,
and what to measure. The adaptive behavior criterion may be irrelevant for many
children; adaptive behavior is impaired in virtually all children who have IQ
scores <50. The major utility of the adaptive behavior criterion is to confirm ID
in children with IQ scores in the 65-75 range. It should be noted that deficits in
adaptive behavior are often found in disorders such as autism spectrum disorder
(ASD; see Chapter 54 ) and attention-deficit/hyperactivity disorder (ADHD; see
Chapter 49 ) in the presence of typical intellectual function.
The issues of measurement are important as well. The independence of the 3
domains of adaptive behavior has not been validated. The relationship between
adaptive behavior and IQ performance is insufficiently explored. Most adults
with mild ID do not have significant impairments in practical skills. Adaptive
behavior deficits also must be distinguished from maladaptive behavior (e.g.,
aggression, inappropriate sexual contact).
 Onset before age 18 yr or adulthood distinguishes dysfunctions that originate
during the developmental period. The diagnosis of ID may be made after 18 yr
of age, but the cognitive and adaptive dysfunction must have been manifested
before age 18.
The term “mental retardation” should not be used because it is stigmatizing,
has been used to limit the achievements of the individual, and has not met its
initial objective of assisting people with the disorder. The term intellectual
disability is increasingly used in its place, but has not been adopted universally.
In the United States, Rosa's law (Public Law 111-256) was passed in 2010 and
now mandates that the term mental retardation be stripped from federal health,
education, and labor policy. As of 2013, at least 9 states persist in using the
outdated terminology. In Europe the term learning disability is often used to
describe ID.
Global developmental delay (GDD) is a term often used to describe young
children whose limitations have not yet resulted in a formal diagnosis of ID. In
DSM-5, GDD is a diagnosis given to children <5 yr of age who display
significant delay (>2 SD) in acquiring early childhood developmental milestones
in 2 or more domains of development. These domains include receptive and
expressive language, gross and fine motor function, cognition, social and
personal development, and activities of daily living. Typically, it is assumed that
delay in 2 domains will be associated with delay across all domains evaluated,
but this is not always the case. Furthermore, not all children who meet criteria
for a GDD diagnosis at a young age go on to meet criteria for ID after age 5 yr.
Reasons for this might include maturational effects, a change in developmental
trajectory (possibly from an intervention), reclassification to a different disability
category, or imprecise use of the GDD diagnosis initially. Conversely, in patients
with more severe delay, the GDD term is often inappropriately used beyond the
point when the child clearly has ID, often by 3 yr of age.
It is important to distinguish the medical diagnosis of GDD from the federal
disability classification of “developmental delay” that may be used by education
agencies under IDEA. This classification requires that a child have delays in
only 1 domain of development with subsequent need for special education. Each
state determines its own precise definition and terms of eligibility under the
broader definition outline by IDEA, and many states use the label for children up
to age 9 yr.
Etiology
Numerous identified causes of ID may occur prenatally, during delivery,
postnatally, or later in childhood. These include infection, trauma, prematurity,
hypoxia-ischemia, toxic exposures, metabolic dysfunction, endocrine
abnormalities, malnutrition, and genetic abnormalities. However, more than two
thirds of persons with ID will not have a readily identifiable underlying
diagnosis that can be linked to their clinical presentation, meriting further
medical evaluation. For those who then undergo further genetic and metabolic
workup, about two thirds will have an etiology that is subsequently discovered.
There does appear to be 2 overlapping populations of children with ID with
differing corresponding etiologies. Mild ID (IQ 50-70) is associated more with
environmental influences, with the highest risk among children of low
socioeconomic status. Severe ID (IQ <50) is more frequently linked to biologic
and genetic causes. Accordingly, diagnostic yield is generally higher among
persons with more severe disability (>75%) than among those with mild
disability (<50%). With continued advancement of technologic standards and
expansion of our knowledge base, the number of identified biologic and genetic
causes is expected to increase.
Nongenetic risk factors that are often associated with mild ID include low
socioeconomic status, residence in a developing country, low maternal
education, malnutrition, and poor access to healthcare. The most common
biologic causes of mild ID include genetic or chromosomal syndromes with
multiple, major, or minor congenital anomalies (e.g., velocardiofacial, Williams,
and Noonan syndromes), intrauterine growth restriction, prematurity, perinatal
insults, intrauterine exposure to drugs of abuse (including alcohol), and sex
chromosomal abnormalities. Familial clustering is common.
In children with severe ID, a biologic cause (usually prenatal) can be
identified in about three fourths of all cases. Causes include chromosomal (e.g.,
Down, Wolf-Hirschhorn, and deletion 1p36 syndromes) and other genetic and
epigenetic disorders (e.g., fragile X, Rett, Angelman, and Prader-Willi
syndromes), abnormalities of brain development (e.g., lissencephaly), and inborn
errors of metabolism or neurodegenerative disorders (e.g.,
mucopolysaccharidoses) (Table 53.1 ). Nonsyndromic severe ID may be a result
of inherited or de novo gene mutations, as well as microdeletions or
microduplications not detected on standard chromosome analysis. Currently,
>700 genes are associated with nonsyndromic ID. Inherited genetic
abnormalities may be mendelian (autosomal dominant de novo, autosomal
recessive, X-linked) or nonmendelian (imprinting, methylation, mitochondrial
defects; see Chapter 97 ). De novo mutations may also cause other phenotypic
features such as seizures or autism; the presence of these features suggests more
pleotropic manifestations of genetic mutations. Consistent with the finding that
disorders altering early embryogenesis are the most common and severe, the
earlier the problem occurs in development, the more severe its consequences
tend to be.

Table 53.1

Identification of Cause in Children With Significant Intellectual Disability

% OF
CAUSE EXAMPLES
TOTAL
Chromosomal disorder Trisomies 21, 18, 13 ~20
Deletions 1p36, 4p, 5p, 11p, 12q, 17p
Microdeletions; 47,XXX
Klinefelter and Turner syndromes
Genetic syndrome Fragile X, Prader-Willi, Angelman, and Rett syndromes ~20
Nonsyndromic autosomal Variations in copy number; de novo mutations in SYNGAP1 , GRIK2 , ~10
mutations TUSC3, oligosaccharyl transferase, and others
Developmental brain Hydrocephalus ± meningomyelocele; schizencephaly, lissencephaly ~8
abnormality
Inborn errors of metabolism or Phenylketonuria, Tay-Sachs disease, various storage diseases ~7
neurodegenerative disorder
Congenital infections HIV, toxoplasmosis, rubella, cytomegalovirus, syphilis, herpes simplex ~3
Familial intellectual disability Environment, syndromic, or genetic ~5
Perinatal causes Hypoxic-ischemic encephalopathy, meningitis, intraventricular 4
hemorrhage, periventricular leukomalacia, fetal alcohol syndrome
Postnatal causes Trauma (abuse), meningitis, hypothyroidism ~4
Unknown 20
Adapted from Stromme P, Hayberg G: Aetiology in severe and mild mental retardation: a
population based study of Norwegian children, Dev Med Child Neurol 42:76–86, 2000.

Etiologic workup is recommended in all cases of GDD or ID. Although there

are only about 80 disorders (all of which are metabolic in nature) for which
treatment may ameliorate the core symptoms of ID, several reasons beyond
disease modification should prompt providers to seek etiologic answers in
patients with ID. These include insight into possible associated medical or
behavioral comorbidities; information on prognosis and life expectancy;
estimation of recurrence risk for family planning counseling, potential
validation, and closure for the family; increased access to services or specific
supports; and better understanding of underlying pathology with the hope of new
eventual treatment options. When surveyed, families of children with ID with no
identified underlying etiology almost universally report that they would want to
know of an etiologic diagnosis if given the choice.

Epidemiology
The prevalence of ID depends on the definition, method of ascertainment, and
population studied, both in terms of geography and age. According to the
statistics of a normal distribution, 2.5% of the population should have ID (based
on IQ alone), and 75% of these individuals should fall into the mild to moderate
range. Variability in rates across populations likely results from the heavy
influence of external environmental factors on the prevalence of mild ID. The
prevalence of severe ID is relatively stable. Globally, the prevalence of ID has
been estimated to be approximately 16.4 per 1,000 persons in low-income
countries, approximately 15.9/1,000 for middle-income countries, and
approximately 9.2/1,000 in high-income countries. A meta-analysis of
worldwide studies from 1980–2009 yielded an overall prevalence of 10.4/1000.
ID occurs more in boys than in girls, at 2 : 1 in mild ID and 1.5 : 1 in severe ID.
In part this may be a consequence of the many X-linked disorders associated
with ID, the most prominent being fragile X syndrome (see Chapter 98.5 ).
In 2014–2015 in the United States, approximately 12/1000 students 3-5 yr old
and 6.2/1000 students 6-21 yr old received services for ID in federally supported
school programs. In 2012 the National Survey of Children's Health reported an
estimated prevalence of ID among American children (age 2-17 yr) of 1.1%. For
several reasons, fewer children than predicted are identified as having mild ID.
Because it is more difficult to diagnose mild ID than the more severe forms,
professionals might defer the diagnosis and give the benefit of the doubt to the
child. Other reasons that contribute to the discrepancy are use of instruments that
underidentify young children with mild ID, children diagnosed as having ASD
without their ID being addressed, misdiagnosis as a language disorder or specific
learning disability, and a disinclination to make the diagnosis in poor or minority
students because of previous overdiagnosis. In some cases, behavioral disorders
may divert the focus from the cognitive dysfunction.
Beyond potential underdiagnosis of mild ID, the number of children with mild
ID may be decreasing as a result of public health and education measures to
prevent prematurity and provide early intervention and Head Start programs.
However, although the number of schoolchildren who receive services under a
federal disability classification of ID has decreased since 1999, when
developmental delay is included in analysis of the data, the numbers have not
changed appreciably.
The prevalence of severe ID has not changed significantly since the 1940s,
accounting for 0.3–0.5% of the population. Many of the causes of severe ID
involve genetic or congenital brain malformations that can neither be anticipated
nor treated at present. In addition, new populations with severe ID have offset
the decreases in the prevalence of severe ID that have resulted from improved
healthcare. Although prenatal diagnosis and subsequent pregnancy terminations
could lead to a decreasing incidence of Down syndrome (see Chapter 98.2 ), and
newborn screening with early treatment has virtually eliminated ID caused by
phenylketonuria and congenital hypothyroidism, continued high prevalence of
fetal exposure to illicit drugs and improved survival of very-low-birthweight
premature infants has counterbalanced this effect.

Pathology and Pathogenesis

The limitations in our knowledge of the neuropathology of ID are exemplified
by 10–20% of brains of persons with severe ID appearing entirely normal on
standard neuropathologic study. Most of these brains show only mild,
nonspecific changes that correlate poorly with the degree of ID, including
microcephaly, gray matter heterotopias in the subcortical white matter, unusually
regular columnar arrangement of the cortex, and neurons that are more tightly
packed than usual. Only a minority of the brain shows more specific changes in
dendritic and synaptic organization, with dysgenesis of dendritic spines or
cortical pyramidal neurons or impaired growth of dendritic trees. The
programming of the central nervous system (CNS) involves a process of
induction ; CNS maturation is defined in terms of genetic, molecular, autocrine,
paracrine, and endocrine influences. Receptors, signaling molecules, and genes
are critical to brain development. The maintenance of different neuronal
phenotypes in the adult brain involves the same genetic transcripts that play a
crucial role in fetal development, with activation of similar intracellular signal
transduction mechanisms.
As the ability to identify genetic aberrations that correspond to particular
phenotypes expands through the use of next-generation sequencing, more will be
elucidated about the pathogenesis of ID at a genetic and molecular level. This
expanding pathophysiologic knowledge base may serve as a framework with
which to develop targeted therapies to bypass or correct newly identified defects.
For example, use of histone deacetylase (HDAC) inhibitors has been shown to
rescue structural and functional neural deficits in mouse models of Kabuki
syndrome, a disorder of histone methylation that leads to variable levels of ID
and characteristic facial features (see Chapter 100 ).

Clinical Manifestations
Early diagnosis of ID facilitates earlier intervention, identification of abilities,
realistic goal setting, easing of parental anxiety, and greater acceptance of the
child in the community. Most children with ID first come to the pediatrician's
attention in infancy because of dysmorphisms, associated developmental
disabilities, or failure to meet age-appropriate developmental milestones (Tables
53.2 and 53.3 ). There are no specific physical characteristics of ID, but
dysmorphisms may be the earliest signs that bring children to the attention of the
pediatrician. They might fall within a genetic syndrome such as Down syndrome
or might be isolated, as in microcephaly or failure to thrive. Associated
developmental disabilities include seizure disorders, cerebral palsy, and ASD.

Table 53.2
Physical Examination of a Child With Suspected
Developmental Disabilities

ITEM POSSIBLE SIGNIFICANCE

General appearance May indicate significant delay in development or obvious syndrome
Stature
Short stature Malnutrition, many genetic syndromes are associated with short stature
(e.g., Turner, Noonan)
Obesity Prader-Willi syndrome
Large stature Sotos syndrome
Head
Macrocephaly Alexander syndrome, Canavan disease, Sotos syndrome,
gangliosidosis, hydrocephalus, mucopolysaccharidosis, subdural
effusion
Microcephaly Virtually any condition that can restrict brain growth (e.g., malnutrition,
Angelman syndrome, Cornelia de Lange syndrome, fetal alcohol
effects)
Face
Coarse, triangular, round, or flat face; Specific measurements may provide clues to inherited, metabolic, or
hypotelorism or hypertelorism; slanted other diseases such as fetal alcohol syndrome, cri du chat (5p−)
or short palpebral fissure; unusual nose, syndrome, or Williams syndrome.
maxilla, and mandible
Eyes
Prominent Crouzon, Seckel, and fragile X syndromes
Cataract Galactosemia, Lowe syndrome, prenatal rubella, hypothyroidism
Cherry-red spot in macula Gangliosidosis (GM1 ), metachromatic leukodystrophy, mucolipidosis,
Tay-Sachs disease, Niemann-Pick disease, Farber lipogranulomatosis,
sialidosis type III
Chorioretinitis Congenital infection with cytomegalovirus, toxoplasmosis, Zika virus,
or rubella
Corneal cloudiness Mucopolysaccharidosis types I and II, Lowe syndrome, congenital
syphilis
Ears
Low-set or malformed pinnae Trisomies such as Down syndrome, Rubinstein-Taybi syndrome,
CHARGE syndrome, cerebrooculofacioskeletal syndrome, fetal
phenytoin effects
Hearing Loss of acuity in mucopolysaccharidosis; hyperacusis in many
encephalopathies
Heart
Structural anomaly or hypertrophy CHARGE syndrome, velocardiofacial syndrome, glycogenosis type II,
fetal alcohol effects, mucopolysaccharidosis type I; chromosomal
anomalies such as Down syndrome; maternal PKU; chronic cyanosis
may impair cognitive development.
Liver
Hepatomegaly Fructose intolerance, galactosemia, glycogenosis types I-IV,
mucopolysaccharidosis types I and II, Niemann-Pick disease, Tay-
Sachs disease, Zellweger syndrome, Gaucher disease, ceroid
lipofuscinosis, gangliosidosis
Genitalia
Macroorchidism Fragile X syndrome
Hypogenitalism Prader-Willi, Klinefelter, and CHARGE syndromes
Extremities
Hands, feet; dermatoglyphics, creases May indicate a specific entity such as Rubinstein-Taybi syndrome or
may be associated with chromosomal anomaly
Joint contractures Signs of muscle imbalance around the joints; e.g., with
meningomyelocele, cerebral palsy, arthrogryposis, muscular dystrophy;
also occurs with cartilaginous problems such as mucopolysaccharidosis
Skin
Café au lait spots Neurofibromatosis, tuberous sclerosis, chromosomal aneuploidy,
ataxia-telangiectasia, multiple endocrine neoplasia type 2b
Fanconi anemia, Gaucher disease
Syndromes: basal cell nevus, McCune-Albright, Silver-Russell,
Bloom, Chediak-Higashi, Hunter, Bannayan-Riley-Ruvalcaba,
Maffucci
Seborrheic or eczematoid rash PKU, histiocytosis
Hemangiomas and telangiectasia Sturge-Weber syndrome, Bloom syndrome, ataxia-telangiectasia
Hypopigmented macules, streaks, Tuberous sclerosis, hypomelanosis of Ito
adenoma sebaceum
Hair
Hirsutism De Lange syndrome, mucopolysaccharidosis, fetal phenytoin effects,
cerebrooculofacioskeletal syndrome, trisomy 18, Wiedemann-Steiner
syndrome (hypertrichosis cubiti)
Neurologic
Asymmetry of strength and tone Focal lesion, hemiplegic cerebral palsy
Hypotonia Prader-Willi, Down, and Angelman syndromes; gangliosidosis; early
cerebral palsy; muscle disorders (dystrophy or myopathy)
 Hypertonia Neurodegenerative conditions involving white matter, cerebral palsy,
trisomy 18
Ataxia Ataxia-telangiectasia, metachromatic leukodystrophy, Angelman
syndrome
CHARGE, Coloboma, heart defects, atresia choanae, retarded growth, genital anomalies, ear
anomalies (deafness); CATCH-22, cardiac defects, abnormal face, thymic hypoplasia, cleft palate,
hypocalcemia—defects on chromosome 22; PKU, phenylketonuria.
From Simms M: Intellectual and developmental disability. In Kliegman RM, Lye PS, Bordini BJ, et
al, editors: Nelson pediatric symptom-based diagnosis, Philadelphia, 2018, Elsevier, Table 24.11,
p 376.

Table 53.3

Examples of Minor Anomalies and Associated Syndromes* †

AREA ANOMALY/SYNDROME
Head Flat occiput: Down syndrome, Zellweger syndrome; prominent occiput: trisomy 18
Delayed closure of sutures: hypothyroidism, hydrocephalus
Craniosynostosis: Crouzon syndrome, Pfeiffer syndrome
Delayed fontanel closure: hypothyroidism, Down syndrome, hydrocephalus, skeletal dysplasias
Face Midface hypoplasia: fetal alcohol syndrome, Down syndrome
Triangular facies: Russell-Silver syndrome, Turner syndrome
Coarse facies: mucopolysaccharidoses, Sotos syndrome
Prominent nose and chin: fragile X syndrome
Flat facies: Apert syndrome, Stickler syndrome
Round facies: Prader-Willi syndrome
Eyes Hypertelorism: fetal hydantoin syndrome, Waardenburg syndrome
Hypotelorism: holoprosencephaly sequence, maternal phenylketonuria effect
Inner canthal folds/Brushfield spots: Down syndrome; slanted palpebral fissures: trisomies
Prominent eyes: Apert syndrome, Beckwith-Wiedemann syndrome
Lisch nodules: neurofibromatosis
Blue sclera: osteogenesis imperfecta, Turner syndrome, hereditary connective tissue disorders
Ears Large pinnae/simple helices: fragile X syndrome
Malformed pinnae/atretic canal: Treacher Collins syndrome, CHARGE syndrome
Low-set ears: Treacher Collins syndrome, trisomies, multiple disorders
Nose Anteverted nares/synophrys: Cornelia de Lange syndrome; broad nasal bridge: fetal drug effects,
fragile X syndrome
Low nasal bridge: achondroplasia, Down syndrome
Prominent nose: Coffin-Lowry syndrome, Smith-Lemli-Opitz syndrome
Mouth Long philtrum/thin vermilion border: fetal alcohol effects
Cleft lip and palate: isolated or part of a syndrome
Micrognathia: Pierre Robin sequence, trisomies, Stickler syndrome
Macroglossia: hypothyroidism, Beckwith-Wiedemann syndrome
Teeth Anodontia: ectodermal dysplasia
Notched incisors: congenital syphilis
Late dental eruption: Hunter syndrome, hypothyroidism
Talon cusps: Rubinstein-Taybi syndrome
Wide-spaced teeth: Cornelia de Lange syndrome, Angelman syndrome
Hair Hirsutism: Hurler syndrome
Low hairline: Klippel-Feil sequence, Turner syndrome
Sparse hair: Menkes disease, argininosuccinic acidemia
 Abnormal hair whorls/posterior whorl: chromosomal aneuploidy (e.g., Down syndrome)
Abnormal eyebrow patterning: Cornelia de Lange syndrome
Neck Webbed neck/low posterior hairline: Turner syndrome, Noonan syndrome
Chest Shield-shaped chest: Turner syndrome
Genitalia Macroorchidism: fragile X syndrome
Hypogonadism: Prader-Willi syndrome
Extremities Short limbs: achondroplasia, rhizomelic chondrodysplasia
Small hands: Prader-Willi syndrome
Clinodactyly: trisomies, including Down syndrome
Polydactyly: trisomy 13, ciliopathies
Broad thumb: Rubinstein-Taybi syndrome
Syndactyly: de Lange syndrome
Transverse palmar crease: Down syndrome
Joint laxity: Down syndrome, fragile X syndrome, Ehlers-Danlos syndrome
Phocomelia: Cornelia de Lange syndrome
Spine Sacral dimple/hairy patch: spina bifida
Skin Hypopigmented macules/adenoma sebaceum: tuberous sclerosis
Café au lait spots and neurofibromas: neurofibromatosis
Linear depigmented nevi: hypomelanosis of Ito
Facial port-wine hemangioma: Sturge-Weber syndrome
Nail hypoplasia or dysplasia: fetal alcohol syndrome, trisomies
*
Increased incidence of minor anomalies have been reported in cerebral palsy, intellectual
disability, learning disabilities, and autism.
†The presence of 3 or more minor anomalies implies a greater chance that the child has a major
anomaly and a diagnosis of a specific syndrome.
CHARGE, Coloboma, heart defects, atresia choanae, retarded growth, genital anomalies, ear
anomalies (deafness).
Modified from Levy SE, Hyman SL. Pediatric assessment of the child with developmental delay,
Pediatr Clin North Am 40:465-477, 1993.

Most children with ID do not keep up with their peers' developmental skills.
In early infancy, failure to meet age-appropriate expectations can include a lack
of visual or auditory responsiveness, unusual muscle tone (hypo- or hypertonia)
or posture, and feeding difficulties. Between 6 and 18 mo of age, gross motor
delay (lack of sitting, crawling, walking) is the most common complaint.
Language delay and behavior problems are common concerns after 18 mo (Table
53.4 ). For some children with mild ID, the diagnosis remains uncertain during
the early school years. It is only after the demands of the school setting increase
over the years, changing from “learning to read” to “reading to learn,” that the
child's limitations are clarified. Adolescents with mild ID are typically up to date
on current trends and are conversant as to “who,” “what,” and “where.” It is not
until the “why” and “how” questions are asked that their limitations become
apparent. If allowed to interact at a superficial level, their mild ID might not be
appreciated, even by professionals, who may be their special education teachers
or healthcare providers. Because of the stigma associated with ID, adolescents
may use euphemisms to avoid being thought of as “stupid” or “retarded” and
may refer to themselves as learning disabled, dyslexic, language disordered, or
slow learners. Some people with ID emulate their social milieu to be accepted.
They may be social chameleons and assume the morals of the group to whom
they are attached. Some would rather be thought “bad” than “incompetent.”

Table 53.4

Common Presentations of Intellectual Disability by Age

AGE AREA OF CONCERN
Newborn Dysmorphic syndromes, (multiple congenital anomalies), microcephaly
Major organ system dysfunction (e.g., feeding, breathing)
Early infancy (2-4 mo) Failure to interact with the environment
Concerns about vision and hearing impairments
Later infancy (6-18 mo) Gross motor delay
Toddlers (2-3 yr) Language delays or difficulties
Preschool (3-5 yr) Language difficulties or delays
Behavior difficulties, including play
Delays in fine motor skills: cutting, coloring, drawing
School age (>5 yr) Academic underachievement
Behavior difficulties (e.g., attention, anxiety, mood, conduct)

Children with ID have a nonprogressive disorder; loss of developmental

milestones or progressive symptoms suggest another disorder (see Chapter 53.1
).

Diagnostic Evaluation
Intellectual disability is one of the most frequent reasons for referral to pediatric
genetic providers, with separate but similar diagnostic evaluation guidelines put
forth by the American College of Medical Genetics, the American Academy of
Neurology, the American Academy of Pediatrics (AAP), and the American
Academy of Child and Adolescent Psychiatry. ID is a diagnosis of great clinical
heterogeneity, with only a subset of syndromic etiologies identifiable through
classic dysmorphology. If diagnosis is not made after conducting an appropriate
history and physical examination, chromosomal microarray is the recommended
first step in the diagnostic evaluation of ID. Next-generation sequencing
represents the new diagnostic frontier, with extensive gene panels (exome or
whole genome) that increase the diagnostic yield and usefulness of genetic
testing in ID. Other commonly used medical diagnostic testing for children with
ID includes neuroimaging, metabolic testing, and electroencephalography (Fig.
53.1 ).

FIG. 53.1 Algorithm for the evaluation of the child with unexplained global
developmental delay (GDD) or intellectual disability (ID). AA, amino acids; ASD, autistic
spectrum disorder; CK, creatine kinase; CSF, cerebrospinal fluid; FBC, full blood count;
GAA, guanidinoacetic acid; GAG, glycosaminoglycans; LFT, liver function test; OA,
organic acids; TFT, thyroid function tests; TSC, tuberous sclerosis complex; U&E, urea
and electrolytes; VLCFA, very long chain fatty acids; WES, whole exome sequencing;
WGS, whole genome sequencing; X-linked intellectual disability genes.

Decisions to pursue an etiologic diagnosis should be based on the medical and

family history, physical examination, and the family's wishes. Table 53.5
summarizes clinical practice guidelines and the yields of testing to assist in
decisions about evaluating the child with GDD or ID. Yield of testing tends
increase with worsening severity of delays.

Table 53.5

Suggested Evaluation of the Child With Intellectual Disability (ID) or Global

Developmental Delay (GDD)
TEST COMMENT
In-depth Includes pre-, peri-, and postnatal events (including seizures); developmental attainments; and 3-
history generation pedigree in family history (focusing on neurologic or developmental abnormalities,
miscarriages, consanguinity, etc.)
 Physical Particular attention to minor or subtle dysmorphisms; growth issues; neurocutaneous
examination findings; eye and skull abnormalities; hepatosplenomegaly; and neurologic examination for
focality
Behavioral phenotype
Vision and Essential to detect and treat; can mask as developmental delay
hearing
evaluation
Gene A 15% yield overall
microarray Better resolution than with karyotype; may identify up to twice as many abnormalities as
analysis karyotyping
Karyotype Yield of 4% in ID/GDD (18.6% if syndromic features, 3% excluding trisomy 21)
Best for inversions and balanced insertions, reciprocal translocations, and polyploidy
Fragile X Combined yield of 2%
screen Preselection on clinical grounds can increase yield to 7.6%
Next- Detects inherited and de novo point mutations, especially in nonsyndromic severe intellectual
generation disability
gene Whole exome sequencing (WES, introduced in 2010) gives an additional yield of about 30–
sequencing 40%.
Although not yet used clinically, pilot studies of whole genome sequencing (WGS) reveal
additional yield of about 15%.
Neuroimaging MRI preferred; positive findings increased by abnormalities of skull contour or microcephaly
and macrocephaly, or focal neurologic examination (30–40% if indicated, 10–14% if
screening).
Identification of specific etiologies is rare; most conditions that are found do not alter the
treatment plan; need to weigh risk of sedation against possible yield.
Thyroid (T4 , Near 0% in settings with universal newborn screening program
TSH)
Serum lead If there are identifiable risk factors for excessive environmental lead exposure (e.g., low
socioeconomic status, home built before 1950)
Metabolic Yield of 0.2–4.6% based on clinical indicators and tests performed
testing Urine organic acids, plasma amino acids, ammonia, lactate, and capillary blood gas
Focused testing based on clinical findings is warranted if lack of newborn screen results or
suggestive history/exam (e.g., regression, consanguinity, hepatosplenomegaly, course facies).
Tandem mass spectrometry newborn screening has allowed for identification of many
disorders in perinatal period and have decreased yield in older children; other disorders have
emerged, such as congenital disorders of glycosylation (yield 1.4%) and disorders of creatine
synthesis and transport (yield 2.8%).
MECP2 for 1.5% of females with criteria suggestive of Rett (e.g., acquired microcephaly, loss of skills)
Rett 0.5% of males
syndrome
EEG May be deferred in absence of history of seizures
Repeated Can give time for maturation of physical and behavioral phenotype; new technology may be
history and available for evaluation.
physical
examination

EEG, Electroencephalogram; CGH, comparative genomic hybridization; MECP2, methyl CpG–

binding protein 2; T4 , thyroxine; TSH, thyroid-stimulating hormone.
Data from Michelson DJ et al: Evidence report. Genetic and metabolic testing on children with
global developmental delay: report of the Quality Standards Subcommittee of the American
Academy of Neurology and the Practice Committee of Child Neurology, Neurology 77:1629-35,
2011; Curry CJ et al: Evaluation of mental retardation: recommendations of a Consensus
Conference: American College of Medical Genetics, Am J Med Genet 12:72:468-477, 1997;
Shapiro BK, Batshaw ML: Mental retardation. In Burg FD et al: Gellis and Kagan's current
pediatric therapy , ed 18, Philadelphia, 2005, Saunders; and Shevell M et al: Practice parameter:
evaluation of the child with global developmental delay, Neurology 60:367–380, 2003.

Microarray analysis has replaced a karyotype as first-tier testing given that it

discerns abnormalities that are far below the resolution of a karyotype.
Microarray analysis may identify variants of unknown significance or benign
variants and therefore should be used in conjunction with a genetic consultation.
Karyotyping has a role when concerns for inversions, balanced insertions, and
reciprocal translocations are present. Fluorescence in situ hybridization (FISH)
and subtelomeric analysis have been largely replaced by microarray analysis but
are occasionally used for specific indications. If microarray analysis is not
diagnostic, whole exome sequencing increases the diagnostic yield in many
children with nonsyndromic severe ID. Starting with whole exome sequencing
may be more cost-effective and may substantially reduce time to diagnosis with
higher ultimate yields compared with the traditional diagnostic pathway.
Molecular genetic testing for fragile X syndrome is recommended for all
children presenting with GDD. Yields are highest in males with moderate ID,
unusual physical features, and/or a family history of ID, or for females with
more subtle cognitive deficits associated with severe shyness and a relevant
family history, including premature ovarian failure or later-onset ataxia-tremor
symptoms. For children with a strong history of X-linked ID, specific testing of
genes or the entire chromosome may be revealing. Testing for Rett syndrome
(MECP2, methyl CpG–binding protein 2) should be considered in girls with
moderate to severe disability.
A child with a progressive neurologic disorder, developmental regression, or
acute behavioral changes needs metabolic investigation as shown in Figure 53.1
. Some are advocating that metabolic testing should be done more frequently in
children with ID because of the possibility of detecting a condition that could be
treatable (Fig. 53.2 and Table 53.6 ). A child with seizure-like episodes should
have an electroencephalogram (EEG), although this testing is generally not
helpful outside the scope of ruling out seizures. MRI of the brain may provide
useful information in directing the care of a child with micro- or macrocephaly,
change in head growth trajectory, asymmetric head shape, new or focal
neurologic findings, or seizure. MRI can detect a significant number of subtle
markers of cerebral dysgenesis in children with ID, but these markers do not
usually suggest a specific etiologic diagnosis.
 FIG. 53.2 Summary of treatable inherent errors of metabolism (IEM) that
can be detected by metabolic tests in affected children, each of which is
affordable and accessible and has the potential to identify at least 2 IEM
(and up to 22). Each bar represents the yield of the specific screening test
and lists the number and types of treatable IEM it can identify. PAA, Plasma
amino acids; tHcy, total homocysteine; ACP, plasma acylcarnitine profile;
UOA, urine organic acids. (From van Karnebeek CD, Stockler S: Treatable
inborn errors of metabolism causing intellectual disability: a systematic
literature review, Mol Genet Metab 105:368–381, 2012, Fig 1, p 374.)

Table 53.6
Treatable Intellectual Disability Endeavor
(TIDE) Diagnostic Protocol
Tier 1: Nontargeted Metabolic Screening to Identify 54 (60%) Treatable
IEM

Blood
Plasma amino acids
Plasma total homocysteine
Acylcarnitine profile
Copper, ceruloplasmin
Urine
Organic acids
 Purines and pyrimidines
Creatine metabolites
Oligosaccharides
Glycosaminoglycans
Amino acids (when indicated)

Tier 2: Current Practice Adhering to International Guidelines* (1 or more

of:)

Audiology
Ophthalmology
Cytogenetic testing (array CGH)
Thyroid studies
Complete blood count (CBC)
Lead
Metabolic testing
Brain MRI and 1H spectroscopy (where available)
Fragile X
Targeted gene sequencing/molecular panel
Other

Tier 3: Targeted Workup to Identify 35 (40%) Treatable IEM Requiring

Specific Testing

According to patient's symptomatology and clinician's expertise

Utilization of digital tools (www.treatable-id.org )
Specific biochemical/gene test
Whole blood manganese
Plasma cholestanol
Plasma 7-dehydroxycholesterol:cholesterol ratio
Plasma pipecolic acid and urine α-amino adipic semialdehyde (AASA)
Plasma very-long-chain fatty acids
Plasma vitamin B12 and folate
Serum and CSF lactate to pyruvate ratio
Enzyme activities (leukocytes): arylsulfatase A, biotinidase,
glucocerebrosidase, fatty aldehyde dehydrogenase
 Urine deoxypyridinoline
CSF amino acids
CSF neurotransmitters
CSF-to-plasma glucose ratio
CoQ measurement: fibroblasts
Molecular analysis: CA5A, NPC1, NPC2, SC4MOL, SLC18A2, SLC19A3,
SLC30A10, SLC52A2, SLC52A3, PDHA1, DLAT, PDHX, SPR, TH genes

IEM, Inborn errors of metabolism; CSF, cerebrospinal fluid; CGH,

comparative genomic hybridization; CoQ, coenzyme Q (ubiquinone).

* Low threshold for ordering tests.

Adapted from Van Karnebeek CD, Stockler-Ipsiroglu S. Early identification of

treatable inborn errors of metabolism in children with intellectual disability: The
Treatable Intellectual Disability Endeavor protocol in British Columbia,
Paediatr Child Health 19(9):469–471, 2014.

Some children with subtle physical or neurologic findings can also have
determinable biologic causes of their ID (see Tables 53.2 and 53.3 ). How
intensively one investigates the cause of a child's ID is based on the following
factors:

◆ What is the degree of delay, and what is the age of

the child? If milder or less pervasive delays are
present, especially in a younger child, etiologic yield
is likely to be lower.
◆ Is the medical history, family history, or physical
exam suggestive of a specific disorder, increasing the
likelihood that a diagnosis will be made? Are the
parents planning on having additional children, and
does the patient have siblings? If so, one may be more
 likely to intensively seek disorders for which prenatal
diagnosis or a specific early treatment option is
available.
◆ What are the parents' wishes? Some parents have
little interest in searching for the cause of the ID,
whereas others become so focused on obtaining a
diagnosis that they have difficulty following through
on interventions until a cause has been found. The
entire spectrum of responses must be respected, and
supportive guidance should be provided in the context
of the parents' education.

Differential Diagnosis
One of the important roles of pediatricians is the early recognition and diagnosis
of cognitive deficits. The developmental surveillance approach to early diagnosis
of ID should be multifaceted. Parents' concerns and observations about their
child's development should be listened to carefully. Medical, genetic, and
environmental risk factors should be recognized. Infants at high risk
(prematurity, maternal substance abuse, perinatal insult) should be registered in
newborn follow-up programs in which they are evaluated periodically for
developmental lags in the 1st 2 yr of life; they should be referred to early
intervention programs as appropriate. Developmental milestones should be
recorded routinely during healthcare maintenance visits. The AAP has
formulated a schema for developmental surveillance and screening (see Chapter
28 ).
Before making the diagnosis of ID, other disorders that affect cognitive
abilities and adaptive behavior should be considered. These include conditions
that mimic ID and others that involve ID as an associated impairment. Sensory
deficits (severe hearing and vision loss), communication disorders, refractory
seizure disorders, poorly controlled mood disorders, or unmanaged severe
attention deficits can mimic ID; certain progressive neurologic disorders can
appear as ID before regression is appreciated. Many children with cerebral palsy
(see Chapter 616.1 ) or ASD (Chapter 54 ) also have ID. Differentiation of
isolated cerebral palsy from ID relies on motor skills being more affected than
cognitive skills and on the presence of pathologic reflexes and tone changes. In
autism spectrum disorders, language and social adaptive skills are more
affected than nonverbal reasoning skills, whereas in ID, there are usually more
equivalent deficits in social, fine motor, adaptive, and cognitive skills.

Diagnostic Psychologic Testing

The formal diagnosis of ID requires the administration of individual tests of
intelligence and adaptive functioning.
The Bayley Scales of Infant and Toddler Development (BSID-III), the most
commonly used infant intelligence test, provides an assessment of cognitive,
language, motor, behavior, social-emotional, and general adaptive abilities
between 1 mo and 42 mo of age. Mental Developmental Index (MDI) and
Psychomotor Development Index (PDI, a measure of motor competence) scores
are derived from the results. The BSID-III permits the differentiation of infants
with severe ID from typically developing infants, but it is less helpful in
distinguishing between a typical child and one with mild ID.
The most commonly used psychologic tests for children older than 3 yr are the
Wechsler Scales. The Wechsler Preschool and Primary Scale of Intelligence,
Fourth Edition (WPPSI-IV) is used for children with mental ages of 2.5-7.6 yr.
The Wechsler Intelligence Scale for Children, Fifth Edition (WISC-V) is used
for children who function above a 6 yr mental age. Both scales contain numerous
subtests in the areas of verbal and performance skills. Although children with ID
usually score below average on all subscale scores, they occasionally score in
the average range in one or more performance areas.
Several normed scales are used in practice to evaluate adaptive functioning.
For example, the Vineland Adaptive Behavior Scale (VABS-3) uses
semistructured interviews with parents and caregivers/teachers to assess adaptive
behavior in 4 domains: communication, daily living skills, socialization, and
motor skills. Other tests of adaptive behavior include the Woodcock-Johnson
Scales of Independent Behavior–Revised, the AAIDD Diagnostic Adaptive
Behavior Scale (DABS), and the Adaptive Behavior Assessment System (ABAS-
3). There is usually (but not always) a good correlation between scores on the
intelligence and adaptive scales. However, it is important to recognize that
adaptive behavior can by influenced by environmentally based opportunities as
well as family or cultural expectations. Basic practical adaptive skills (feeding,
dressing, hygiene) are more responsive to remedial efforts than is the IQ score.
Adaptive abilities are also more variable over time, which may be related to the
underlying condition and environmental expectations.

Complications
Children with ID have higher rates of vision, hearing, neurologic, orthopedic,
and behavioral or emotional disorders than typically developing children. These
other problems are often detected later in children with ID. If untreated, the
associated impairments can adversely affect the individual's outcome more than
the ID itself.
The more severe the ID, the greater are the number and severity of associated
impairments. Knowing the cause of the ID can help predict which associated
impairments are most likely to occur. Fragile X syndrome and fetal alcohol
syndrome (see Chapter 126.3 ) are associated with a high rate of behavioral
disorders; Down syndrome has many medical complications (hypothyroidism,
obstructive sleep apnea, congenital heart disease, atlantoaxial subluxation).
Associated impairments can require ongoing physical therapy, occupational
therapy, speech-language therapy, behavioral therapy, adaptive and mobility
equipment, glasses, hearing aids, and medication. Failure to identify and treat
these impairments adequately can hinder successful habilitation and result in
difficulties in the school, home, and neighborhood environment.

Prevention
Examples of primary programs to prevent ID include the following:

◆ Increasing the public's awareness of the adverse

effects of alcohol and other drugs of abuse on the
fetus (the most common preventable cause of ID in
the Western world is fetal alcohol exposure).
◆ Encouraging safe sexual practices, preventing teen
pregnancy, and promoting early prenatal care with a
 focus on preventive programs to limit transmission of
diseases that may cause congenital infection (syphilis,
toxoplasmosis, cytomegalovirus, HIV).
◆ Preventing traumatic injury by encouraging the use
of guards, railings, and window locks to prevent falls
and other avoidable injuries in the home; using
appropriate seat restraints when driving; wearing a
safety helmet when biking or skateboarding; limiting
exposure to firearms.
◆ Preventing poisonings by teaching parents about
locking up medications and potential poisons.
◆ Implementing immunization programs to reduce
the risk of ID caused by encephalitis, meningitis, and
congenital infection.
Presymptomatic detection of certain disorders can result in treatment that
prevents adverse consequences. State newborn screening by tandem mass
spectrometry (now including >50 rare genetic disorders in most states), newborn
hearing screening, and preschool lead poisoning prevention programs are
examples. Additionally, screening for comorbid conditions can help to limit the
extent of disability and maximize level of functioning in certain populations.
Annual thyroid, vision, and hearing screening in a child with Down syndrome is
an example of presymptomatic testing in a disorder associated with ID.

Treatment
Although the core symptoms of ID itself are generally not treatable, many
associated impairments are amenable to intervention and therefore benefit from
early identification. Most children with an ID do not have a behavioral or
emotional disorder as an associated impairment, but challenging behaviors
(aggression, self-injury, oppositional defiant behavior) and mental illness (mood
and anxiety disorders) occur with greater frequency in this population than
among children with typical intelligence. These behavioral and emotional
disorders are the primary cause for out-of-home placements, increased family
stress, reduced employment prospects, and decreased opportunities for social
integration. Some behavioral and emotional disorders are difficult to diagnose in
children with more severe ID because of the child's limited abilities to
understand, communicate, interpret, or generalize. Other disorders are masked
by the ID. The detection of ADHD (see Chapter 49 ) in the presence of moderate
to severe ID may be difficult, as may be discerning a thought disorder
(psychosis) in someone with autism and ID.
Although mental illness is generally of biologic origin and responds to
medication, behavioral disorders can result from a mismatch between the
child's abilities and the demands of the situation, organic problems, and family
difficulties. These behaviors may represent attempts by the child to
communicate, gain attention, or avoid frustration. In assessing the challenging
behavior, one must also consider whether it is inappropriate for the child's
mental age, rather than the chronological age. When intervention is needed, an
environmental change, such as a more appropriate classroom setting, may
improve certain behavior problems. Behavior management techniques are
useful; psychopharmacologic agents may be appropriate in certain situations.
No medication has been found that improves the core symptoms of ID.
However, several agents are being tested in specific disorders with known
biologic mechanisms (e.g., mGluR5 inhibitors in fragile X syndrome, mTOR
inhibitors in tuberous sclerosis), with the hope for future pharmacologic options
that could alter the natural course of cognitive impairment seen in patients with
these disorders. Currently, medication is most useful in the treatment of
associated behavioral and psychiatric disorders. Psychopharmacology is
generally directed at specific symptom complexes, including ADHD (stimulant
medication), self-injurious behavior and aggression (antipsychotics), and
anxiety, obsessive-compulsive disorder, and depression (selective serotonin
reuptake inhibitors). Even if a medication proves successful, its use should be
reevaluated at least yearly to assess the need for continued treatment.

Supportive Care and Management

Each child with ID needs a medical home with a pediatrician who is readily
accessible to the family to answer questions, help coordinate care, and discuss
concerns. Pediatricians can have effects on patients and their families that are
still felt decades later. The role of the pediatrician includes involvement in
prevention efforts, early diagnosis, identification of associated deficits, referral
for appropriate diagnostic and therapeutic services, interdisciplinary
management, provision of primary care, and advocacy for the child and family.
The management strategies for children with an ID should be multimodal, with
efforts directed at all aspects of the child's life: health, education, social and
recreational activities, behavior problems, and associated impairments. Support
for parents and siblings should also be provided.

Primary Care
For children with an ID, primary care has the following important components:

◆ Provision of the same primary care received by all

other children of similar chronological age.
◆ Anticipatory guidance relevant to the child's level
of function: feeding, toileting, school, accident
prevention, sexuality education.
◆ Assessment of issues that are relevant to that child's
disorder, such as dental examination in children who
exhibit bruxism, thyroid function in children with
Down syndrome, and cardiac function in Williams
syndrome (see Chapter 454.5 ).
The AAP has published a series of guidelines for children with specific
genetic disorders associated with ID (Down syndrome, fragile X syndrome, and
Williams syndrome). Goals should be considered and programs adjusted as
needed during the primary care visit. Decisions should also be made about what
additional information is required for future planning or to explain why the child
is not meeting expectations. Other evaluations, such as formal psychologic or
educational testing, may need to be scheduled.
Interdisciplinary Management
The pediatrician has the responsibility for consulting with other disciplines to
make the diagnosis of ID and coordinate treatment services. Consultant services
may include psychology, speech-language pathology, physical therapy,
occupational therapy, audiology, nutrition, nursing, and social work, as well as
medical specialties such as neurodevelopmental disabilities, neurology, genetics,
physical medicine and rehabilitation, psychiatry, developmental-behavioral
pediatricians, and surgical specialties. Contact with early intervention and school
personnel is equally important to help prepare and assess the adequacy of the
child's individual family service plan or individual educational plan. The family
should be an integral part of the planning and direction of this process. Care
should be family centered and culturally sensitive; for older children, their
participation in planning and decision-making should be promoted to whatever
extent possible.

Periodic Reevaluation
The child's abilities and the family's needs change over time. As the child grows,
more information must be provided to the child and family, goals must be
reassessed, and programming needs should be adjusted. A periodic review
should include information about the child's health status as well as the child's
functioning at home, at school, and in other community settings. Other
information, such as formal psychologic or educational testing, may be helpful.
Reevaluation should be undertaken at routine intervals (every 6-12 mo during
early childhood), at any time the child is not meeting expectations, or when the
child is moving from one service delivery system to another. This is especially
true during the transition to adulthood, beginning at age 16, as mandated by the
IDEA Amendments of 2004, and lasting through age 21, when care should be
transitioned to adult-based systems and providers.

Federal and Education Services

Education is the single most important discipline involved in the treatment of
children with an ID. The educational program must be relevant to the child's
needs and address the child's individual strengths and weaknesses. The child's
developmental level, requirements for support, and goals for independence
provide a basis for establishing an individualized education program (IEP) for
school-age children, as mandated by federal legislation.
Beyond education services, families of children with ID are often in great
need of federal or state-provided social services. All states offer developmental
disabilities programs that provide home and community-based services to
eligible children and adults, potentially including in-home supports, care
coordination services, residential living arrangements, and additional therapeutic
options. A variety of Medicaid waiver programs are also offered for children
with disabilities within each state. Children with ID who live in low
socioeconomic status households should qualify to receive supplemental security
income (SSI). Of note, in 2012, an estimated >40% of children with ID did not
receive SSI benefits for which they would have been eligible, indicating an
untapped potential resource for many families.

Leisure and Recreational Activities

The child's social and recreational needs should be addressed. Although young
children with ID are generally included in play activities with children who have
typical development, adolescents with ID often do not have opportunities for
appropriate social interactions. Community participation among adults with ID is
much lower than that of the typical population, stressing the importance of
promoting involvement in social activities such as dances, trips, dating,
extracurricular sports, and other social-recreational events at an early age.
Participation in sports should be encouraged (even if the child is not
competitive) because it offers many benefits, including weight management,
development of physical coordination, maintenance of cardiovascular fitness,
and improvement of self-image.

Family Counseling
Many families adapt well to having a child with ID, but some have emotional or
social difficulties. The risks of parental depression and child abuse and neglect
are higher in this group of children than in the general population. The factors
associated with good family coping and parenting skills include stability of the
marriage, good parental self-esteem, limited number of siblings, higher
socioeconomic status, lower degree of disability or associated impairments
(especially behavioral), parents' appropriate expectations and acceptance of the
diagnosis, supportive extended family members, and availability of community
programs and respite care services. In families in whom the emotional burden of
having a child with ID is great, family counseling, parent support groups, respite
care, and home health services should be an integral part of the treatment plan.

Transition to Adulthood
Transition to adulthood in adolescents with intellectual disabilities can present a
stressful and chaotic time for both the individual and the family, just as it does
among young adults of typical intelligence. A successful transition strongly
correlates to later improved quality of life but requires significant advanced
planning. In moving from child to adult care, families tend to find that policies,
systems, and services are more fragmented, less readily available, and more
difficult to navigate. Several domains of transition must be addressed, such as
education and employment, health and living, finances and independence, and
social and community life. Specific issues to manage include transitioning to an
adult healthcare provider, determining the need for decision-making assistance
(e.g., guardianship, medical power of attorney), securing government benefits
after aging out of youth-based programs (e.g., SSI, medical assistance), agreeing
on the optimal housing situation, applying for state disability assistance
programs, and addressing caretaker estate planning as it applies to the individual
with ID (e.g., special needs trusts).
Following graduation from high school, options for continued education or
entry into the workforce should be thoroughly considered, with the greater goal
of ultimate community-based employment. Although employment is a critical
element of life adaptation for persons with ID, only 15% are estimated to have
jobs, with significant gaps in pay and compensation compared to workers
without disability. Early planning and expansion of opportunities can help to
reduce barriers to employment. Post–secondary education possibilities might
involve community college or vocational training. Employment selection should
be “customized” to the individual's interests and abilities. Options may include
participation in competitive employment, supported employment, high school–
to–work transition programs, job-coaching programs, and consumer-directed
voucher programs.

Prognosis
In children with severe ID, the prognosis is often evident by early childhood.
Mild ID might not always be a lifelong disorder. Children might meet criteria for
GDD at an early age, but later the disability can evolve into a more specific
developmental disorder (communication disorder, autism, specific learning
disability, or borderline normal intelligence). Others with a diagnosis of mild ID
during their school years may develop sufficient adaptive behavior skills that
they no longer fit the diagnosis as adolescents or young adults, or the effects of
maturation and plasticity may result in children moving from one diagnostic
category to another (from moderate to mild ID). Conversely, some children who
have a diagnosis of a specific learning disability or communication disorder
might not maintain their rate of cognitive growth and may fall into the range of
ID over time.
The apparent higher prevalence of ID in low- and middle-income countries is
of concern given the limitations in available resources. Community-based
rehabilitation (CBR) is an effort promoted by WHO over the past 4 decades as
a means of making use of existing community resources for persons with
disabilities in low-income countries with the goal of increasing inclusion and
participation within the community. CBR is now being implemented in >90
countries, although the efficacy of such programs has not been established.
The long-term outcome of persons with ID depends on the underlying cause,
degree of cognitive and adaptive deficits, presence of associated medical and
developmental impairments, capabilities of the families, and school and
community supports, services, and training provided to the child and family
(Table 53.7 ). As adults, many persons with mild ID are capable of gaining
economic and social independence with functional literacy, but they may need
periodic supervision (especially when under social or economic stress). Most
live successfully in the community, either independently or in supervised
settings.

Table 53.7

Severity of Intellectual Disability and Adult-Age Functioning

MENTAL
LEVEL AGE AS ADULT ADAPTATION
ADULT
Mild 9-11 yr Reads at 4th-5th grade level; simple multiplication and division; writes simple letter, lists;
completes job application; basic independent job skills (arrive on time, stay at task, interact
with coworkers); uses public transportation, might qualify for driver's license; keeps house,
cooks using recipes
Moderate 6-8 yr Sight-word reading; copies information (e.g., address from card to job application);
 matches written number to number of items; recognizes time on clock; communicates;
some independence in self-care; housekeeping with supervision or cue cards; meal
preparation, can follow picture recipe cards; job skills learned with much repetition; uses
public transportation with some supervision
Severe 3-5 yr Needs continuous support and supervision; might communicate wants and needs,
sometimes with augmentative communication techniques
Profound <3 yr Limitations of self-care, continence, communication, and mobility; might need complete
custodial or nursing care
Data from World Health Organization: International Statistical Classification of Diseases and
Related Health Problems, 10th revision, Geneva, 2011, WHO.

For persons with moderate ID, the goals of education are to enhance adaptive
abilities and “survival” academic and vocational skills so they are better able to
live and function in the adult world (Table 53.7 ). The concept of supported
employment has been very beneficial to these individuals; the person is trained
by a coach to do a specific job in the setting where the person is to work,
bypassing the need for a “sheltered workshop” experience and resulting in
successful work adaptation in the community. These persons generally live at
home or in a supervised setting in the community.
As adults, people with severe to profound ID usually require extensive to
pervasive supports (Table 53.7 ). These individuals may have associated
impairments, such as cerebral palsy, behavioral disorders, epilepsy, or sensory
impairments, that further limit their adaptive functioning. They can perform
simple tasks in supervised settings. Most people with this level of ID can live in
the community with appropriate supports.
The life expectancy of people with mild ID is similar to the general
population, with a mean age at death in the early 70s. However, persons with
severe and profound ID have a decreased life expectancy at all ages, presumably
from associated serious neurologic or medical disorders, with a mean age at
death in the mid-50s. Given that persons with ID are living longer and have high
rates of comorbid health conditions in adulthood (e.g., obesity, hypertension,
diabetes), ID is now one of the costliest ICD-10 diagnoses, with an average
lifetime cost of 1-2 million dollars per person. Thus the priorities for
pediatricians are to improve healthcare delivery systems during childhood,
facilitate the transition of care to adult providers, and ensure high-quality,
integrated community-based services for all persons with ID.

53.1
Intellectual Disability With
Regression
Bruce K. Shapiro, Meghan E. O'Neill

The patients discussed in Chapter 53 with intellectual disability (ID) usually

have a static and nonprogressive disease course. They may acquire new
developmental milestones, although at a slower rate than unaffected children, or
they may remain fixed at a particular developmental stage. Regression of
milestones in these children may be caused by increasing spasticity or
contractures, new-onset seizures or a movement disorder, or the progression of
hydrocephalus.
Nonetheless, regression or loss of milestones should suggest a progressive
encephalopathy caused by an inborn error of metabolism, including disorders
of energy metabolism and storage disorders, or a neurodegenerative disorder,
including disorders of the whole brain (diffuse encephalopathies), white matter
(leukodystrophies), cerebral cortex, and basal ganglia as well as spinocerebellar
disorders (Table 53.8 ) (see Chapters 616 and 617 ).
Table 53.8
Causes of Progressive Encephalopathy
Onset Before Age 2 Years
Acquired Immunodeficiency Syndrome Encephalopathy *
Disorders of Amino Acid Metabolism

Guanidinoacetate methyltransferase deficiency*

Homocystinuria (21q22)*
Maple syrup urine disease (intermediate and thiamine response forms)*
Phenylketonuria
Guanidinoacetate methyltransferase deficiency*
Hyperammonemic disorders
Disorders of Lysosomal Enzymes

Ganglioside storage disorders

GM1 gangliosidosis
GM2 gangliosidosis (Tay-Sachs disease, Sandhoff disease)
Gaucher disease type II (glucosylceramide lipidosis)*
Globoid cell leukodystrophy (Krabbe disease)
Glycoprotein degradation disorders
I-cell disease
Mucopolysaccharidoses*
Type I (Hurler Syndrome)*
Type III (Sanfilippo disease)
Niemann-Pick disease type A (sphingomyelin lipidosis)
Sulfatase deficiency disorders
Metachromatic leukodystrophy (sulfatide lipidoses)
Multiple sulfatase deficiency

Carbohydrate-Deficient Glycoprotein Syndromes

Hypothyroidism *
Mitochondrial Disorders

Alexander disease
Mitochondrial myopathy, encephalopathy, lactic acidosis, stroke
Progressive infantile poliodystrophy (Alpers disease)
Subacute necrotizing encephalomyelopathy (Leigh disease)
Trichopoliodystrophy (Menkes disease)

Neurocutaneous Syndromes

Chediak-Higashi syndrome
Neurofibromatosis*
Tuberous sclerosis*

Other Disorders of Gray Matter

 Infantile ceroid lipofuscinosis (Santavuori-Haltia disease)
Infantile neuroaxonal dystrophy
Lesch-Nyhan disease*
Progressive neuronal degeneration with liver disease
Rett syndrome

Progressive Hydrocephalus *
Other Disorders of White Matter

Aspartoacylase deficiency (Canavan disease)

Galactosemia: Transferase deficiency*
Neonatal adrenoleukodystrophy
Pelizaeus-Merzbacher disease
Progressive cavitating leukoencephalopathy

Onset After Age 2 Years

Disorders of Lysosomal Enzymes

Gaucher disease type III (glucosylceramide lipidosis)

Globoid cell leukodystrophy (late-onset Krabbe disease)
Glycoprotein degradation disorders
Aspartylglycosaminuria
Mannosidosis type II
GM2 gangliosidosis (juvenile Tay-Sachs disease)
Metachromatic leukodystrophy (late-onset sulfatide lipidoses)
Mucopolysaccharidoses types II and VII
Niemann-Pick type C (sphingomyelin lipidosis)

Infectious Disease

Acquired immunodeficiency syndrome encephalopathy*

Congenital syphilis*
Subacute sclerosing panencephalitis

Other Disorders of Gray Matter

 Ceroid lipofuscinosis
Juvenile
Late infantile (Bielschowsky-Jansky disease)
Huntington disease
Mitochondrial disorders
Late-onset poliodystrophy
Myoclonic epilepsy and ragged-red fibers
Progressive neuronal degeneration with liver disease
Xeroderma pigmentosum

Other Disorders of White Matter

Adrenoleukodystrophy
Alexander disease
Cerebrotendinous xanthomatosis
Progressive cavitating leukoencephalopathy

Other Diseases

Wilson disease
Friedreich ataxia
Pantothenate kinase neurodegeneration
Neurodegeneration with brain iron accumulation

* Denotes the most common conditions and those with disease-modifying

treatment.

From Pina-Garza JE: Fenichel's clinical pediatric neurology, ed 7, Philadelphia,

2013, Elsevier, Boxes 5-2 and 5-5, pp 114, 121.

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CHAPTER 54

Autism Spectrum Disorder

Carolyn F. Bridgemohan

Definition
Autism spectrum disorder (ASD) is a neurobiologic disorder with onset in
early childhood. The key features are impairment in social communication and
social interaction accompanied by restricted and repetitive behaviors. The
presentation of ASD can vary significantly from one individual to another, as
well as over the course of development for a particular child. There is currently
no diagnostic biomarker for ASD. Accurate diagnosis therefore requires careful
review of the history and direct observation of the child's behavior.

Diagnostic Criteria and Symptoms

The diagnostic criteria in the Diagnostic and Statistical Manual, Fifth Edition
(DSM-5) focus on symptoms in two primary domains (Table 54.1 ). To meet
criteria for ASD, the symptoms need to have been present since the early
developmental period, significantly impact functioning, and not be better
explained by the diagnoses of intellectual disability (ID) or global developmental
delay (GDD; Chapter 53 ). Table 54.2 provides associated features not included
in DSM-5 criteria.
Table 54.1
DSM-5 Diagnostic Criteria for Autism
Spectrum Disorder
A. Persistent deficits in social communication and social interaction across
 multiple contexts, as manifested by the following, currently or by history:
1. Deficits in social-emotional reciprocity.
2. Deficits in nonverbal communicative behaviors used for social
interaction.
3. Deficits in developing, maintaining, and understanding
relationships.
B. Restricted, repetitive patterns of behavior, interests, or activities, as
manifested by at least 2 of the following, currently or by history:
1. Stereotyped or repetitive motor movements, use of objects, or
speech.
2. Insistence on sameness, inflexible adherence to routines, or
ritualized patterns of verbal or nonverbal behavior.
3. Highly restricted, fixated interests that are abnormal in intensity
or focus.
4. Hyper- or hyporeactivity to sensory input or unusual interest in
sensory aspects of the environment.
C. Symptoms must be present in the early developmental period (may not
become fully manifest until social demands exceed limited capacities, or
may be masked by learned strategies in later life).
D. Symptoms cause clinically significant impairment in social, occupational,
or other important areas of current functioning.
E. These disturbances are not better explained by intellectual disability
(intellectual developmental disorder) or global developmental delay.

From the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition,
(Copyright 2013). American Psychiatric Association, pp 50–51.
Table 54.2
Associated Features of Autism Not in DSM-5
Criteria

Atypical language development and abilities

Age <6 yr: frequently disordered and delayed in comprehension;
two-thirds have difficulty with expressive phonology and
grammar
Age ≥6 yr: disordered pragmatics, semantics, and morphology,
 with relatively intact articulation and syntax (i.e., early
difficulties are resolved)
Motor abnormalities: motor delay; hypotonia; catatonia; deficits in
coordination, movement preparation and planning, praxis, gait, and
balance

For version with full references, see Diagnostic and Statistical Manual of Mental
Disorders, Fifth Edition, Washington DC, 2013, American Psychiatric
Association. Adapted from Lai MC, Lombardo MV, Baron-Cohen S: Autism,
Lancet 383:896–910, 2014.

Previously, ASD was grouped under the heading of pervasive developmental

disorders (PDDs) and included a variety of subdiagnoses, including autistic
disorder, PDD not otherwise specified (PDD-NOS), and Asperger disorder .
Research did not support these as distinct conditions; in the current diagnostic
framework, any individual previously diagnosed with 1 of these conditions
should be diagnosed with ASD.
Symptoms can present early in infancy, with reduced response to name and
unusual use of objects being strong predictors for risk of ASD. However,
symptoms before age 12 mo are not as reliably predictive of later diagnosis.
Individuals with milder severity may not present until preschool or school age,
when the social demands for peer interaction and group participation are higher.

Social Communication and Social Interaction

Individuals with ASD have difficulty understanding and engaging in social
relationships. The problems are pervasive and impact 3 major areas: reciprocal
social interactions (social-emotional reciprocity), nonverbal communication, and
understanding of social relationships. The presentation can vary with severity
and developmental functioning. Diagnosis of ASD requires the presence of
symptoms from all 3 categories (Table 54.3 ).
Table 54.3
Signs and Symptoms of Possible Autism in
Preschool Children (or Equivalent Mental
Age)
Social Interaction and Reciprocal Communication Behaviors
Spoken Language

Language delay (in babbling or using words; e.g., using <10 words by age
2 yr).
Regression in, or loss of, use of speech.
Spoken language (if present) may include unusual features, such as
vocalizations that are not speech-like; odd or flat intonation; frequent
repetition of set words and phrases (echolalia); reference to self by name
or “you” or “she” or “he” beyond age 3 yr.
Reduced and/or infrequent use of language for communication; e.g., use of
single words, although able to speak in sentences.

Responding to Others

Absent or delayed response to name being called, despite normal hearing.

Reduced or absent responsive social smiling.
Reduced or absent responsiveness to other people's facial expressions or
feelings.
Unusually negative response to the requests of others (“demand avoidance”
behavior).
Rejection of cuddles initiated by parent or caregiver, although the child
may initiate cuddles.

Interacting With Others

Reduced or absent awareness of personal space, or unusually intolerant of

people entering their personal space.
Reduced or absent social interest in others, including children of own age
—may reject others; if interested in others, child may approach others
inappropriately, seeming to be aggressive or disruptive.
Reduced or absent imitation of others' actions.
Reduced or absent initiation of social play with others; plays alone.
Reduced or absent enjoyment of situations that most children like; e.g.,
birthday parties.
Reduced or absent sharing of enjoyment.
Eye Contact, Pointing, and Other Gestures

Reduced or absent use of gestures and facial expressions to communicate

(although may place an adult's hand on objects).
Reduced and poorly integrated gestures, facial expressions, body
orientation, eye contact (looking at people's eyes when speaking), and
speech used in social communication.
Reduced or absent social use of eye contact (assuming adequate vision).
Reduced or absent “joint attention” (when 1 person alerts another to
something by means of gazing, finger pointing, or other verbal or
nonverbal indication for the purpose of sharing interest). This would be
evident in the child from lack of:
Gaze switching
Following a point (looking where the other person points to—may
look at hand)
Using pointing at or showing objects to share interest

Ideas and Imagination

Reduced or absent imagination and variety of pretend play.

Unusual or Restricted Interests and/or Rigid and Repetitive Behaviors

Repetitive “stereotypic” movements such as hand flapping, body rocking

while standing, spinning, and finger flicking.
Repetitive or stereotyped play; e.g., opening and closing doors.
Over focused or unusual interests.
Excessive insistence on following own agenda.
Extremes of emotional reactivity to change or new situations; insistence on
things being “the same.”
Overreaction or underreaction to sensory stimuli, such as textures, sounds,
or smells.
Excessive reaction to the taste, smell, texture, or appearance of food, or
having extreme food fads.

Adapted from Baird G, Douglas HR, Murphy MS: Recognizing and diagnosing
autism in children and young people: summary of NICE guidance. BMJ
343:d6360, 2011, Box 1, p 901.

Social-Emotional Reciprocity
Reduced social interactions in ASD may range from active avoidance or reduced
social response to having an interest in, but lacking ability to initiate or sustain,
an interaction with peers or adults. A young child with ASD may not respond
when his name is called, may exhibit limited showing and sharing behaviors, and
may prefer solitary play. In addition, the child may avoid attempts by others to
play and may not participate in activities that require taking turns, such as peek-
a-boo and ball play. An older child with ASD may have an interest in peers but
may not know how to initiate or join in play. The child may have trouble with
the rules of conversation and may either talk at length about an area of interest or
abruptly exit the interaction. Younger children often have limited capacity for
imaginative or pretend play skills. Older children may engage in play but lack
flexibility and may be highly directive to peers. Some children with ASD
interact well with adults but struggle to interact with same-age peers.

Nonverbal Communicative Behavior

Difficulties with nonverbal communication may manifest as reduced use of eye
contact and gestures such as pointing. Children may also show reduced
awareness or response to the eye gaze or pointing of others. They may use eye
contact only when communicating a highly preferred request or may have
difficulty coordinating the use of nonverbal with verbal communication.
Children with ASD may have limited range of facial expression or expressed
emotion.

Developing, Maintaining, and Understanding

Relationships
Children with ASD have limited insight regarding social relationships. They
have difficulty understanding the difference between a true friend and a casual
acquaintance. They have trouble picking up on the nuances of social interactions
and understanding social expectations for polite behavior. They may have
reduced understanding of personal boundaries and may stand too close to others.
In addition, they can have trouble understanding and inferring others' emotions
and are less likely to share emotion or enjoyment with others. Adolescents and
young adults have difficulty engaging in group interactions and navigating
romantic relationships.

Restrictive and Repetitive Behavior

Diagnosis of ASD requires the presence of 2 of the 4 symptoms of restrictive
and repetitive patterns of behavior discussed next.

Stereotyped Motor Movements or Speech

Stereotyped (or stereotypic) movements and repetitive behaviors may include
hand flapping, finger movements, body rocking and lunging, jumping, running
and spinning, and repetitive speech such as echoing words immediately after
they are said. Repetitive patterns of play may be present, such as lining up
objects, repetitively turning light switches on and off or opening and closing
doors, spinning objects, or arranging toys in a specific manner. These repetitive
patterns may not be seen in very young toddlers but may develop as they get
older. Stereotyped movements can change over time and in older children are
seen more often in individuals with lower cognitive functioning.

Insistence on Sameness
Children with ASD have difficulty tolerating transitions or change. They may
insist on certain routines or schedules and can become very distressed with
unexpected events or new situations. They may repeat scripts from shows or
movies or watch the same portion of a video repeatedly. Intolerance for change
causes significant impairment and impact on child and family function.

Restricted Interests
This symptom may manifest as intense interests that seem out of the norm in
comparison to same-age peers. Younger children may play with a limited range
of toys or may insist on retaining a small object in each hand. Older children
may have a strong preference for a particular story or movie. The area of interest
may be shared by peers (e.g., Disney movies, Legos, Thomas the Train) but
unusual in its intensity. Other affected children may have interests that are both
intense and odd, such as an interest in brands of vehicles, license plate numbers,
or fans and heating systems. These interests interfere with social interactions; a
child may only want to talk about her area of interest or may insist that peers act
out a particular story in a rigid and inflexible manner.

Hypo- or Hyperreactivity to Sensory Input

Children with ASD may be overly sensitive to sensory input, such as noise,
smells, or texture. Children may scream when they hear a siren or vacuum and
may gag and choke with certain foods or odors. They may refuse to wear certain
clothing or may become very distressed with bathing or with cutting nails and
hair. Conversely, some affected children seem to crave sensory input. They may
engage in repetitive jumping or hugging and may smell or lick objects or people.
Young children may inappropriately touch the face or hair of others.
Diagnosing ASD with DSM-5 criteria can be challenging in very young
children because of reduced expression of repetitive behaviors, particularly
stereotyped behavior and intense interests. Studies monitoring development in
high-risk young children who have an older sibling with ASD indicate these
additional symptoms may emerge over time. This creates a dilemma for
specialty clinicians evaluating very young children for ASD, because they may
not be able to endorse sufficient symptoms to make an early diagnosis and
access specialized intervention services.

Severity Levels Defined in DSM-5

Severity level in ASD is based on the level of support the individual requires in
each of the major domains impacted—social communication and restricted and
repetitive behavior. Levels range from –“needing support” (level 1), to
–“needing substantial support” (level 2), to –“needing very substantial support”
(level 3) (Table 54.4 ).

Table 54.4

DSM-5 Severity Levels for Autism Spectrum Disorder

SEVERITY RESTRICTED, REPETITIVE
SOCIAL COMMUNICATION
LEVEL BEHAVIORS
Level 3 Severe deficits in verbal and nonverbal social communication Inflexibility of behavior,
“Requiring skills cause severe impairments in functioning, very limited extreme difficulty coping with
very initiation of social interactions, and minimal response to social change, or other
substantial overtures from others. For example, a person with few words restricted/repetitive behaviors
support” of intelligible speech who rarely initiates interaction and, markedly interfere with
when he or she does, makes unusual approaches to meet needs functioning in all spheres. Great
 only and responds to only very direct social approaches distress/difficulty changing
focus or action.
Level 2 Marked deficits in verbal and nonverbal social communication Inflexibility of behavior,
“Requiring skills; social impairments apparent even with supports in difficulty coping with change, or
substantial place; limited initiation of social interactions; and reduced or other restricted/repetitive
support” abnormal responses to social overtures from others. For behaviors appear frequently
example, a person who speaks simple sentences, whose enough to be obvious to the
interaction is limited to narrow special interests, and who has casual observer and interfere
markedly odd nonverbal communication with functioning in a variety of
contexts. Distress and/or
difficulty changing focus or
action.
Level 1 Without supports in place, deficits in social communication Inflexibility of behavior causes
“Requiring cause noticeable impairments. Difficulty initiating social significant interference with
support” interactions, and clear examples of atypical or unsuccessful functioning in one or more
responses to social overtures of others. May appear to have contexts. Difficulty switching
decreased interest in social interactions. For example, a person between activities. Problems of
who is able to speak in full sentences and engages in organization and planning
communication but whose to-and-fro conversation with others hamper independence.
fails, and whose attempts to make friends are odd and
typically unsuccessful
From the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (Copyright 2013).
American Psychiatric Association, p 52.

Specifiers Defined in DSM-5

Formal diagnosis of ASD also includes documenting associated conditions
including whether the individual has cognitive and/or language impairment, any
related medical, genetic or environmental factors and any other
neurodevelopmental or behavioral health conditions, including catatonia (Table
54.5 ). This process helps to better characterize the presentation in an individual
child and ensures that the diagnosis has been made by considering the symptoms
in the context of the child's current cognitive and language abilities.

Table 54.5
Common Co-occurring Conditions in Autism Spectrum
Disorder (ASD)

INDIVIDUALS
WITH
COMORBIDITY COMMENTS
AUTISM
AFFECTED
DEVELOPMENTAL DISORDERS
Intellectual ~45% Prevalence estimate is affected by the diagnostic boundary and
disability definition of intelligence (e.g., whether verbal ability is used as a
criterion).
 In individuals, discrepant performance between subtests is common.
Language disorders Variable In DSM-IV, language delay was a defining feature of autism (autistic
disorder), but is no longer included in DSM-5.
An autism-specific language profile (separate from language
disorders) exists, but with substantial interindividual variability.
Attention- 28–44% In DSM-IV, not diagnosed when occurring in individuals with autism, but
deficit/hyperactivity no longer so in DSM-5.
disorder
Tic disorders 14–38% ~6⋅5% have Tourette syndrome.
Motor abnormality ≤79% See Table 54.2 .
GENERAL MEDICAL DISORDERS
Epilepsy 8–35% Increased frequency in individuals with intellectual disability or
genetic syndromes.
Two peaks of onset: early childhood and adolescence.
Increases risk of poor outcome.
Gastrointestinal 9–70% Common symptoms include chronic constipation, abdominal pain,
problems chronic diarrhea, and gastroesophageal reflux.
Associated disorders include gastritis, esophagitis, gastroesophageal
reflux disease, inflammatory bowel disease, celiac disease, Crohn
disease, and colitis.
Immune ≤38% Associated with allergic and autoimmune disorders.
dysregulation
Genetic disorders 10–20% Collectively called syndromic autism.
Examples include fragile X syndrome (21–50% of individuals
affected have autism), Rett syndrome (most have autistic features but
with profiles different from idiopathic autism), tuberous sclerosis
complex (24–60%), Down syndrome (5–39%), phenylketonuria (5–
20%), CHARGE syndrome* (15–50%), Angelman syndrome (50–
81%), Timothy syndrome (60–70%), and Joubert syndrome (~40%).
Sleep disorders 50–80% Insomnia is the most common.
PSYCHIATRIC DISORDERS
Anxiety ~40% Common across all age-groups.
Most common are social anxiety disorder (13–29% of individuals
with autism) and generalized anxiety disorder (13–22%).
High-functioning individuals are more susceptible (or symptoms are
more detectable).
Depression 12–70% Common in adults, less common in children.
High-functioning adults who are less socially impaired are more
susceptible (or symptoms are more detectable).
Obsessive- 7–24% Shares the repetitive behavior domain with autism that could cut
compulsive disorder across nosologic categories.
(OCD) Important to distinguish between repetitive behaviors that do not
involve intrusive, anxiety-causing thoughts or obsessions (part of
autism) and those that do (and are part of OCD).
Psychotic disorders 12–17% Mainly in adults.
Most commonly recurrent hallucinosis.
High frequency of autism-like features (even a diagnosis of ASD)
preceding adult-onset (52%) and childhood-onset schizophrenia (30–
50%).
Substance use ≤16% Potentially because individual is using substances as self-medication to
disorders relieve anxiety.
Oppositional 16–28% Oppositional behaviors could be a manifestation of anxiety, resistance to
defiant disorder change, stubborn belief in the correctness of own point of view, difficulty
seeing another's point of view, poor awareness of the effect of own
behavior on others, or no interest in social compliance.
 Eating disorders 4–5% Could be a misdiagnosis of autism, particularly in females, because both
involve rigid behavior, inflexible cognition, self-focus, and focus on
details.
PERSONALITY DISORDERS †
Paranoid 0–19% Could be secondary to difficulty understanding others' intentions and
personality disorder negative interpersonal experiences.
Schizoid 21–26% Partly overlapping diagnostic criteria.
personality disorder
Schizotypal 2–13% Some overlapping criteria, especially those shared with schizoid
personality disorder personality disorder.
Borderline 0–9% Could have similarity in behaviors (e.g., difficulties in interpersonal
personality disorder relationships, misattributing hostile intentions, problems with affect
regulation), which requires careful differential diagnosis.
Could be a misdiagnosis of autism, particularly in females.
Obsessive- 19–32% Partly overlapping diagnostic criteria.
compulsive
personality disorder
Avoidant 13–25% Could be secondary to repeated failure in social experiences.
personality disorder
BEHAVIORAL DISORDERS
Aggressive ≤68% Often directed toward caregivers rather than noncaregivers.
behaviors Could be a result of empathy difficulties, anxiety, sensory overload,
disruption of routines, and difficulties with communication.
Self-injurious ≤50% Associated with impulsivity and hyperactivity, negative affect, and
behaviors lower levels of ability and speech.
Could signal frustration in individuals with reduced communication,
as well as anxiety, sensory overload, or disruption of routines.
Could also become a repetitive habit.
Could cause tissue damage and need for restraint.
Pica ~36% More likely in individuals with intellectual disability.
Could be a result of a lack of social conformity to cultural categories
of what is deemed edible, or sensory exploration, or both.
Suicidal ideation or 11–14% Risks increase with concurrent depression and behavioral problems, and
attempt after being teased or bullied.
*Coloboma of the eye; heart defects; atresia of the choanae; retardation of growth and
development, or both; genital and urinary abnormalities, or both; and ear abnormalities and
deafness.
†
Particularly in high-functioning adults.
DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, 4th edition ; DSM-5, Diagnostic
and Statistical Manual of Mental Disorders, Fifth edition.
Adapted from Lai MC, Lombardo MV, Baron-Cohen S: Autism, Lancet 383:896–910, 2014.

Epidemiology
The prevalence of ASD is estimated at 1 in 59 persons by the U.S. Centers for
Disease Control and Prevention (CDC). The prevalence increased significantly
over the past 25 years, primarily because of improved diagnosis and case finding
as well as inclusion of less severe presentations within the autism spectrum.
There is a 4:1 male predominance. The prevalence is increased in siblings (up to
10% recurrence rate) and particularly in identical twins. There are no racial or
ethnic differences in prevalence. Individuals from racial minorities and lower
socioeconomic status are at risk for later diagnosis.

Etiology
The etiology of ASD is thought to result from disrupted neural connectivity and
is primarily impacted by genetic variations affecting early brain development.
Animal models and studies of individuals with ASD indicate changes in brain
volume and neural cell density in the limbic system, cerebellum, and
frontotemporal regions. One study documented changes in early brain
development, characterized as “hyperexpansion of cortical surface area,” at age
6-12 mo on brain MRI, which correlated with later development of impaired
social skills. Functional studies show abnormalities of processing information,
particularly related to foundational social skills such as facial recognition. The
disruptions in early brain development likely are responsive the treatment. Early
developmental therapies in young children with ASD have demonstrated the
capacity for normalization of electrophysiologic response to visual stimuli,
including faces.
Numerous genes involved in brain development and synaptic function have
been associated with ASD. Mutations that include large genetic deletions or
duplications and small sequencing changes have been implicated; these can be
inherited or occur de novo. Heterozygous mutations in genes, such as present in
deletion or duplication of 15q11.2 or 16p11.2, may have variable expression
within a family. Rare recessive mutations have been implicated in some
populations with high levels of consanguinity. Patients with a number of genetic
syndromes (e.g., fragile X, Down, Smith-Lemli-Opitz, Rett, Angelman, Timothy,
Joubert) as well as disorders of metabolism and mitochondrial function have
higher rates of ASD than the general population (Table 54.5 ).
There is also evidence for environmental contributions to ASD. Older
maternal or paternal age may increase the risk of ASD. In addition, factors
influencing the intrauterine environment, such as maternal obesity or
overweight, short interval from prior pregnancy, premature birth, and certain
prenatal infections (e.g., rubella, cytomegalovirus) are associated with ASD. An
epigenetic model is considered one explanation for the etiology; individuals with
genetic vulnerability may be more sensitive to environmental factors influencing
early brain development.
Despite frequent concerns from families that vaccines or the preservatives in
vaccines lead to ASD, there is no evidence to support this claim. Multiple
research studies and meta-analyses have failed to show an association of
vaccines with ASD.

Differential Diagnosis
The differential diagnosis of ASD is complex because many conditions in the
differential can also occur with ASD. The most important conditions to consider
in young children are language disorder (see Chapter 52 ), intellectual disability
or global developmental delay (Chapter 53 ), and hearing loss (Chapter 655 ).
Children with language disorder may have impairments in social
communication and play; their social and play skills, however, are typically on
par with their language level. In addition, they do not have associated restricted
and repetitive behavior or atypical use of language, such as scripting. The
diagnosis of social communication disorder is also distinguished from ASD by
the lack of restrictive and repetitive behaviors. Children with intellectual
disability (ID) or global developmental delay (GDD) may have delays in
social and communication skills as well as stereotyped behavior. However, social
and communication skills are typically commensurate with their cognitive and
adaptive functioning. Children with hearing loss may present with some “red
flags” for ASD, such as poor response to name. However, they typically develop
nonverbal communication and play skills as expected and do not have
stereotyped or restricted behavior patterns.
In older children, disorders of attention, learning, and mood regulation must
be considered in the differential diagnosis of ASD. Children with attention-
deficit/hyperactivity disorder (ADHD) may present with reduced eye contact
and response to name caused by poor attention rather than lack of social
awareness. Children with ADHD, however, do not have associated impairments
in shared enjoyment and social reciprocity or repetitive behaviors. Children with
social anxiety or other anxiety disorders may present with some symptoms
suggestive of ASD. Shy children may have reduced eye contact and social
initiation. Anxious children can be resistant to change and prefer familiar
routines. Children with anxiety, however, typically will have preserved social
interest and insight and will not exhibit high levels of stereotyped behaviors.
Reactive attachment disorder can be difficult to distinguish from ASD,
particularly in younger children with history of trauma. However, social
behaviors in these children generally improve with positive caretaking.
The differentiation of ASD from obsessive-compulsive disorder (OCD) ,
tics, and stereotyped behaviors can sometimes be challenging. In general,
stereotyped behaviors may be calming or preferred, whereas tics and compulsive
routines are distressing to the individual. Children with OCD have intense
interests as well as repetitive behaviors and rituals but do not have impairment in
social communication or interaction. Children with stereotypic movement
disorder will not have impaired social skills or other types of restricted and
repetitive behaviors. Children with Landau Kleffner syndrome (LKS) present
with loss of skills in language comprehension (auditory verbal agnosia) and
verbal expression (aphasia) associated with onset of epileptic seizures during
sleep (see Chapter 52 ). In contrast to ASD, children with LKS present with
typical early development followed by loss of language function at age 3-6 yr.

Comorbid Conditions
Up to 50% of individuals with ASD have intellectual disability, ranging in
severity from mild to severe (Table 54.5 ). Intellectual disability is associated
with higher rates of both identified genetic conditions and epilepsy. Children
with ASD often have associated language impairments, including delays in
expressive, receptive, and pragmatic (social) language skills. Language function
can range widely from nonverbal status to age appropriate. Gastrointestinal (GI)
problems such as constipation, esophagitis, and gastroesophageal reflux disease
(GERD) are reported in up to 70% of children with ASD. Epilepsy occurs in up
to 35% of children with ASD and presents in 2 peaks, in early childhood and in
adolescence. Epilepsy or electrical seizures without motor manifestations may be
a cause of regression in young children with ASD.
Children with ASD are at higher risk for disorders of attention, including
reduced attention for nonpreferred activities and excessive attention for preferred
activities. A subset of children will also meet full criteria for a diagnosis of
ADHD. There are higher rates of anxiety (~40%) and mood disorders in ASD,
particularly during adolescence. Children with ASD are also at increased risk for
being bullied and may present with secondary irritability, anxiety, or depression.
Sleep problems, including delayed sleep onset, frequent night waking, and
abnormal sleep architecture, are reported in 50–80% of children with ASD.
There is some evidence for baseline abnormalities in melatonin secretion. The
use of screen-based activities such as television, computers, or tablets before
bedtime can inhibit melatonin secretion. Children with ASD also have higher
rates of feeding and toileting problems resulting from resistance to change,
sensory sensitivity, and repetitive behavior patterns. Many children with ASD
have restrictive feeding patterns and food selectivity. They also have higher rates
of overweight, possibly because of diets higher in carbohydrates, reduced
physical activity, use of food rewards to regulate behavior, and side effects from
medications used for managing mood and behavior.
Disruptive behaviors such as self-injury and aggression are common in ASD
patients, but most common in individuals with lower cognitive function and
limited language. Sleep deprivation, nutritional deficits, pain, epilepsy, and
medication side effects may contribute to disruptive behaviors.

Screening
The American Academy of Pediatrics recommends screening for ASD for all
children at age 18 mo and 24 mo (see Chapter 28 ). Screening should also occur
when there is increased risk for ASD, such as a child with an older sibling who
has ASD, or concern for possible ASD. Screening can be done by parent
checklist or direct assessment. The most frequently used screening tool is the
Modified Checklist for Autism, Revised/Follow-Up Interview (MCHAT-R/FU), a
20-item parent report measure, with additional parent interview completed for
intermediate scores. The MCHAT-R/FU can be used from age 16-30 mo.

Assessment
Diagnostic assessment should include medical evaluation and assessment of the
child's cognitive, language, and adaptive function. Assessment may occur in a
single multidisciplinary visit or through a series of visits with different
developmental specialists. Multidisciplinary evaluation with clinicians who have
expertise with ASD is optimal for diagnostic accuracy and treatment planning.
Developmental-behavioral pediatricians, neurodevelopmental disability
specialists, neurologists, psychiatrists, and psychologists are qualified to make a
formal diagnosis of ASD. Other specialists, including speech-language
pathologists and occupational therapists, should also be included depending on
the child's age and the presenting concerns.
Assessment of ASD includes direct observation of the child to evaluate social
skills and behavior. Informal observation can be supplemented with structured
diagnostic tools such as the Autism Diagnostic Observation Schedule, Second
Edition (ADOS-2) and Autism Diagnostic Observation Schedule, Toddler
module (ADOS-T). These structured play-based assessments provide social
prompts and opportunities to evaluate the frequency and quality of a child's
social responsiveness to, initiation, and maintenance of social interactions; the
capacity for joint attention and shared enjoyment; the child's behavioral
flexibility; and presence of repetitive patterns of behavior. The ADOS-2 and
ADOS-T are not required for accurate diagnosis and do not stand alone, but
rather can be used to augment a careful history and observation. The Childhood
Autism Rating Scale, Second Edition (CARS-2) is a 15-item direct clinical
observation instrument that can assist clinicians in the diagnosis of ASD. The
Autism Diagnostic Interview-Revised (ADI-R) is a lengthy clinical interview tool
that is used primarily in research settings since it takes several hours to
administer. Other tools include standardized rating scales that parents and
teachers can complete to report on the child's social skills and behaviors.
Medical evaluation should include a thorough history and detailed physical
examination of the child, including direct behavioral observations of
communication and play. In addition, the examination should include
measurement of head circumference, careful evaluation for dysmorphic features,
and screening for tuberous sclerosis with Wood lamp exam. Children with ASD
should have genetic testing (described later), an audiology examination to rule
out hearing loss, and in children with pica, a lead test (Table 54.6 ).
Table 54.6
Medical and Genetic Evaluation of Children
With Autism Spectrum Disorder
Physical Examination

Dysmorphic physical features

Muscle tone and reflexes
Head circumference
Wood lamp examination for tuberous sclerosis
Diagnostic Testing

Chromosomal microarray (CMA) in all individuals

Fragile X DNA test in males
Audiology evaluation
Lead test in children with pica

Additional Targeted Genetic Testing

Fragile X DNA test in females with symptoms suggestive of fragile X,

family history of X-linked intellectual disability, tremor, ataxia, or
premature ovarian failure
MeCP2 sequencing in females
PTEN mutation testing if head circumference >2.5 SD above the mean
MeCP2 deletion/duplication testing in males with significant
developmental regression, drooling, respiratory infections, and hypotonia
Karyotype if unable to obtain CMA or if balanced translocation suspected

Additional Targeted Diagnostic Testing

EEG in children with seizures, staring spells, or developmental regression

Brain MRI in children with microcephaly, focal neurologic findings, or
developmental regression
Metabolic testing in children with developmental regression, hypotonia,
seizures, food intolerance, hearing loss, ataxia, or course facial features

Data from Schaefer GB, Mendelsohn NJ: Clinical genetics evaluation in

identifying the etiology of autism spectrum disorders: 2013 guideline revisions,
Genet Med 15(5):399–407, 2013.

There are currently several specialty-specific clinical guidelines for genetic

evaluation of children diagnosed with ASD. Genetic testing is shown to impact
clinical decision-making, but no studies have evaluated the impact of genetic
testing on the outcome for the child. The American College of Medical Genetics
recommends a tiered approach to genetic testing.
First Tier
All children with ASD should have a chromosomal microarray (CMA) . CMA
will be positive in 10–15% of individuals with ASD. The rate is increased to
almost 30% in individuals who have complex presentations, such as associated
microcephaly, dysmorphic features, congenital anomalies, or seizures. CMA
technology will identify copy number variants but not DNA sequencing errors,
balanced translocations, or abnormalities in trinucleotide repeat length. Fragile
X DNA testing is therefore recommended for all boys with ASD. Fragile X testing
should also be considered in girls with physical features suggestive of fragile X
syndrome or with a family history of fragile X, X-linked pattern of intellectual
disability, tremor/ataxia, or premature ovarian failure.

Second Tier
Girls with ASD should have testing for mutation in the MeCP2 gene if CMA is
normal. Boys who have hypotonia, drooling, and frequent respiratory infections
should have MeCP2 deletion/duplication testing. All individuals with ASD and a
head circumference greater than 2.5 standard deviations (SD) above the mean
should have testing for mutation in the PTEN gene because there is a risk for
hamartoma tumor disorders (Cowden, Proteus-like, Bannayan-Riley-Ruvakaba
syndromes) in these individuals. Cytogenetic testing (karyotype) has a lower
yield than CMA. Karyotype is recommended if microarray is not available and
in children with suspected balanced translocation, such as history of multiple
prior miscarriages.
Further medical diagnostic testing is indicated by the child's history and
presentation. Brain imaging is indicated in cases of microcephaly, significant
developmental regression, or focal findings on neurologic examination. Because
of the high rate (up to 25%) of macrocephaly in ASD, imaging is not indicated
for macrocephaly alone. MRI is not recommended for minor language regression
(loss of a few words) during the 2nd year of life that is often described in
toddlers with ASD. Children with concern for seizures, spells, or developmental
regression should have an electroencephalogram (EEG). Metabolic screening is
indicated for children with signs of a metabolic or mitochondrial disorder, such
as developmental regression, weakness, fatigue, lethargy, cyclic vomiting, or
seizures (see Chapters 53 and 102 ).
Treatment and Management
Educational
The primary treatment for ASD is done outside the medical setting and includes
developmental and educational programming. Numerous resources have been
developed that can help families in the complex process of treatment planning
(Table 54.7 ). Intensive behavioral therapies have the strongest evidence to date.
Earlier age at initiation of treatment and higher intensity of treatment are
associated with better outcomes. Programming must be individualized, and no
approach is successful for all children. In addition, research treatments are often
conducted with a high level of intensity and fidelity that are difficult to scale up
or reproduce in community settings. Higher cognitive, play, and joint attention
skills and lower symptom severity at baseline are predictors for better outcomes
in core symptoms, intellectual function, and language function.
Table 54.7
Autism Resources for Families

Autism Speaks First 100 Days kit

https://www.autismspeaks.org/family-services/tool-kits/100-day-
kit
Autism Speaks Toolkits–dental, transition, guardianship
https://www.autismspeaks.org/family-services/tool-kits
AACAP Autism Spectrum Disorder Parent's Medication Guide
https://www.aacap.org/App_Themes/AACAP/Docs/resource_centers/autism/Au
Sexuality information for individuals with developmental disability
http://vkc.mc.vanderbilt.edu/healthybodies/

Behavioral approaches based on the principles of applied behavioral

analysis (ABA) involve direct incremental teaching of skills within a traditional
behavioral framework using reinforcement of desired behavior, careful data
collection, and analysis and adjustment of the treatment program based on
review of data. Comprehensive models integrating behavioral and
developmental approaches that build on key foundational skills, such as joint
attention, shared enjoyment, and reciprocal communication, show strong
evidence of efficacy for young children, particularly toddlers, with ASD.
Examples include the Early Start Denver Model (ESDM), Joint Attention
Symbolic Play Engagement and Regulation (JASPER), and Social
Communication/Emotional Regulation/Transactional Support (SCERTS). Parent
training models also show promise for younger children.
Educational approaches such as the Treatment and Education of Autistic and
Communication Handicapped Children (TEACCH) incorporate structured
teaching, visual supports, and adjustment of the environment to the individual
needs of students with ASD, such as difficulty with communication,
understanding time, and need for routine. These approaches have demonstrated
efficacy for improved cognitive and adaptive skills. For older children with more
severe symptoms, approaches that use behavioral principles in addition to
adjusting the environment may be most effective.
Speech and language therapy can help build vocabulary, comprehension, and
pragmatic skills. Children with ASD benefit from visual supports for
comprehension, understanding expectations, and communicating their needs.
Augmentative communication approaches using photographs or picture icons
can improve comprehension and ability to communicate. There are a range of
options with varying levels of complexity, flexibility, and technology. Using
augmentative communication does not inhibit acquisition of verbal language. On
the contrary, supporting a child's language development with augmentative
supports can facilitate the development of spoken language, even in older
children.
Additional strategies to build social skills are used for school age children and
adolescents and may be administered in the school or community setting by a
variety of specialists, including speech therapists, psychologists, and counselors.
Social skills programs that include training peer mentors have higher rates of
efficacy. Occupational and physical therapy may be indicated for individuals
with motor delay and difficulty acquiring adaptive skills such as dressing and
toileting.
For some high school students with ASD, training in life skills and vocational
skills is critical for maximizing independence in adulthood. Training may focus
on basic self-care (e.g., dressing, hygiene), functional academics (e.g., money
management, banking skills), learning to fill out a job application, and
understanding how to behave with strangers and in work settings. Social skills
and job coaching may be needed even for adolescents with strong cognitive and
academic function, because they may struggle with social perception and may be
vulnerable to exploitation by others.
Co-occurring Conditions
Additional medical or behavioral health treatment is often required for
management of co-occurring conditions in ASD. Seizures occur in up to 35% of
children with ASD and should be managed with appropriate antiepileptic therapy
(see Chapter 611 ). GI problems (e.g., constipation, esophagitis, GERD) may
present with nonspecific irritability, sleep disturbance, self-injury, aggression,
and signs of pain or discomfort, such as crying, and can be managed with the
same approaches used in typically developing children.
Management of co-occurring attention and mood disorders is similar to that
for typically developing children. Strategies to increase structure and
organization in the environment and use of visual supports (e.g., schedules) can
improve attention and reduce anxiety. Some children with ASD benefit from
modified cognitive-behavioral therapy to address anxiety and OCD.
Strategies to promote sleep hygiene and use of behavioral approaches, such as
structured bedtime routines, can address delayed sleep onset. Other medical
problems, such as epilepsy or GERD, can also contribute to poor sleep and
should be treated directly. In cases refractory to behavioral approaches,
medications may be used. (For further discussion of management of sleep
problems, see Chapter 31 .)
Structured behavioral approaches for delayed toilet training in concert with
treatment to prevent constipation are often needed for children with ASD. For
children with highly restrictive diets, nutrition counseling and behaviorally based
feeding therapy may be needed to address poor caloric intake or lack of
nutritional quality. Because of limited diets, children with ASD may be at risk
for low levels of calcium, vitamin D, and iron. Children who are overweight may
have poor nutrition as a result of restrictive diets.
Irritability is a nonspecific symptom and can be a reflection of pain, anxiety,
distress, or lack of sleep. Children with ASD are prone to irritability because of
their difficulty tolerating change and their limited communication skills.
Management of irritability includes evaluating carefully for medical problems
that may be causing pain, as well as for any factors in the child's home or school
environment that may be causing distress. Possible causes of distress range from
common experiences such as changes in the routine to undisclosed abuse or
bullying. Treatment should be targeted first at any underlying cause. Medications
are often used to treat irritability in ASD but should only be used after
appropriate behavioral and communication supports have been implemented.
Pharmacology
There are currently no medications that treat the core symptoms of ASD.
Medications can be used to target specific co-occurring conditions or symptoms
(Table 54.8 ; see also Table 54.5 ). Families should be cautioned, however, that
the effect size may be lower and the rate of medication side effects higher in
children with ASD.

Table 54.8
Common Pharmacologic Treatments in Autism Spectrum
Disorder (ASD)

TARGET MEDICATION
EFFECTS SIDE EFFECTS MONITORING
SYMPTOM CLASS*
Hyperactivity Stimulants Decreased Activation, irritability, emotional Height, weight, BP,
and/or hyperactivity, lability, lethargy/social HR
Inattention impulsivity, improved withdrawal, stomach ache,
attention reduced appetite, insomnia,
increased stereotypy
α2 -Agonists Decreased Drowsiness, irritability, enuresis, Height, weight, BP,
hyperactivity, decreased appetite, dry mouth, HR
impulsivity, improved hypotension
attention
Selective Decreased Irritability, decreased appetite, Height, weight, BP,
norepinephrine hyperactivity, fatigue, stomach ache, nausea, HR
reuptake impulsivity, improved vomiting, racing heart rate
inhibitor attention
Anxiety Selective Decreased anxiety Activation, hyperactivity, Weight, BP, HR
serotonin inattention, sedation, change
reuptake in appetite, insomnia,
inhibitors stomach ache, diarrhea
Citalopram: prolonged QTc
interval
Irritability Atypical Decreased irritability, Somnolence, weight gain, Weight, BP, HR
antipsychotics aggression, self- extrapyramidal movements, Monitor CBC,
(risperidone, injurious behavior, drooling, tremor, dizziness, cholesterol,
aripiprazole) repetitive behavior, vomiting, gynecomastia ALT, AST,
hyperactivity prolactin,
glucose or
hemoglobin
A1c
Insomnia Melatonin Shortened sleep onset Nightmares, enuresis —
*
Specific medications names are provided in parentheses when there is a FDA-approved
indication for the use of the medication to treat the symptom in children with ASD. Further
information about these medications is available in Chapter 33 .
BP, Blood pressure; HR, heart rate; CBC, complete blood count; ALT, alanine transaminase; AST,
aspartate transaminase.
 Preliminary data suggest that intranasal therapy with neuropeptide oxytocin
may improve social functioning in children with ASD, particularly those with
low pretreatment oxytocin levels.
There is evidence to support use of stimulant medication, atomoxetine and α-
agonists for ADHD in ASD. Selective serotonin reuptake inhibitors (SSRI) can
be used for anxiety and OCD and in adolescents may also be useful for
depression. Benzodiazepines may be useful for situational anxiety, for example,
triggered by dental and medical procedures or air travel. Medications used to
treat ADHD and anxiety may result in activation or irritability in ASD and
require careful monitoring.
Melatonin can be used to improve sleep onset but will not address night
waking. Clonidine or trazodone may be used for sleep onset and maintenance.
No medications are specifically labeled for treatment of insomnia in ASD.
The α-adrenergic agonists may be helpful in children who present with
significant behavioral dysregulation. There are two atypical antipsychotic
medications that have U.S. Food and Drug Administration (FDA)
recommendation for irritability and aggression in children with ASD. Both
risperidone and aripiprazole have several studies documenting efficacy for
reducing irritability, aggression, and self-injury. Secondary improvements in
attention and repetitive behavior were also noted. Side effects include weight
gain and metabolic syndrome as well as tardive dyskinesia and extrapyramidal
movements. Careful laboratory monitoring is recommended. Mood-stabilizing
antiepileptic medications have also been used to treat irritability.

Complementary and Alternative Medicine

Families of children with ASD often use complementary and alternative
medicine (CAM) approaches. These treatments can include supplements, dietary
changes, and body or physical treatments. There is a limited evidence to inform
families, who often learn about these treatments from friends and family
members, alternative medicine providers, or the internet. For most therapies,
evidence is insufficient to show benefit. There is strong evidence that secretin
and facilitated communication are not effective. Some therapies, such as
hyperbaric oxygen, chelation, and high-dose vitamins, are potentially harmful.
For children with restrictive diets, taking a daily multivitamin and 400 IU
vitamin D may be indicated, although there is no evidence to support megadoses
of vitamins. Similarly, for children with evidence of gluten sensitivity, a trial of
gluten-free diet may be indicated. However, current evidence does not support
this as a treatment for all children with ASD.
When discussing CAM with a family, it is best to use open and collaborative
communication, encouraging them to share their current practices and any
questions. Specifically ask if they use any herbal treatments, supplements, or
other therapies, such as acupuncture, massage, or chiropractic treatment, and
what they have observed since trying the treatment. Provide accurate
information regarding potential benefit and risk for any treatment. Educate about
“red flags” such as treatments that are marketed as a cure for multiple
conditions, that report no risk of side effects, or that are marketed by the
clinician recommending the treatment. Encourage families to identify a target
symptom, “try one thing at a time,” and monitor response carefully.

Transition
Navigating a successful transition to adult care is a key role for the pediatric
provider. This process should ideally start as early as age 12-13 yr. Parents are
faced with a complex and disconnected system of diverse agencies that they
need to navigate. Use of structured-visit templates and care coordinators can
help ensure that families and their youth with ASD are able to make appropriate
decisions about secondary and postsecondary educational programming,
vocational training, guardianship, finances, housing, and medical care. High
school educational programming should include individualized and meaningful
vocational training, as well as instruction regarding sexuality, relationships,
safety and abuse prevention, finances, travel training, and general self-advocacy.
Individuals with ASD who are higher functioning will need help accessing
supports for college or postsecondary skills training and may benefit from
referral to their state vocational rehabilitative services as well as personal life
coaches or counselors. Families who have adult children with more significant
cognitive disability need information about the range of adult disability services,
how to apply for supplemental security income (SSI), and the process for
considering guardianship or medical and financial conservatorship for their adult
child. These decisions are complex and must be individualized for the adult with
ASD and the family.

Outcome
Autism spectrum disorder is a lifelong condition. Although a minority of
individuals respond so well to therapy that they no longer meet criteria for the
diagnosis, most will make progress but continue to have some impairment in
social and behavioral function as adults. Adult outcome studies are sobering,
indicating that many adults with ASD are socially isolated, lack gainful
employment or independent living, and have higher rates of depression and
anxiety. It is not clear if these data can be extrapolated to younger children
currently receiving intensive educational therapies. There is a growing network
of adult self-advocates who promote the unique strengths in individuals with
ASD. Outcome as measured by developmental progress and functional
independence is better for individuals who have higher cognitive and language
skills and lower ASD severity at initial diagnosis.

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