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Cerebral palsy: Epidemiology, etiology, and prevention

AUTHORS: Elizabeth Barkoudah, MD, Bhooma Aravamuthan, MD, DPhil
SECTION EDITOR: Ann Tilton, MD
DEPUTY EDITOR: Richard P Goddeau, Jr, DO, FAHA

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Jul 2024.

This topic last updated: Feb 27, 2024.

INTRODUCTION

Cerebral palsy (CP) refers to a heterogeneous group of conditions involving permanent

motor dysfunction that affects muscle tone, posture, and/or movement. These conditions
are due to abnormalities of the developing fetal or infant brain resulting from a variety of
non-progressive causes. Although the disorder itself is not neurodegenerative, the clinical
expression may change over time as the central nervous system matures. The motor
impairment results in limitations in functional abilities and activity, which can vary in severity.
Multiple additional symptoms often accompany the primary motor abnormalities, including
altered sensation or perception, intellectual disability, communication and behavioral
difficulties, seizures, and musculoskeletal complications [1].

The epidemiology, etiology, and prevention of CP are reviewed here. The classification,
clinical features, evaluation, diagnosis, management, and prognosis of CP are discussed
separately:

● (See "Cerebral palsy: Classification and clinical features".)

● (See "Cerebral palsy: Evaluation and diagnosis".)

● (See "Cerebral palsy: Overview of management and prognosis".)

● (See "Cerebral palsy: Treatment of spasticity, dystonia, and associated orthopedic

issues".)

EPIDEMIOLOGY
Prevalence — The overall prevalence of CP is approximately 2 per 1000 live births in the
United States but may be up to 3to 4 per 1000 live births in other parts of the world [2-9].

The prevalence of CP is far higher in preterm compared with term infants and increases with
decreasing gestational age (GA) and birth weight (BW), as discussed below. (See 'Prematurity'
below.)

Although infants born preterm are at higher risk of developing CP, preterm infants account
for less than one-half of cases of CP. In large epidemiologic studies of children with CP in
high-income countries, approximately 25 percent were very preterm (GA <32 weeks), 10 to
20 percent were moderately preterm or late preterm (GA 32 to 36 weeks), and 60 percent
were born at term (GA >36 weeks) [3,10].

In other parts of the world, postnatal etiologies like infection may be more common causes,
perhaps due to reduced survival of children born preterm [7,8]. (See 'Specific causes and risk
factors' below.)

Trends over time — In the 1960s through 1980s, the rate of CP and the extent of disability
among preterm infants increased as survival improved for the most premature [11]. During
the 1980s and 1990s, there was a reversal in this trend, most likely because of improvements
in perinatal care. In one study, the prevalence of CP among very low birth weight (VLBW;
<1500 g) infants declined from 6 percent in the early 1980s to 4 by the mid-1990s [12]. This
improvement occurred despite overall increases in survival and multiple births and
decreases in mean BW among this group. In another study, the prevalence of CP among
preterm infants (GA 20 to 27 weeks) decreased from 16 percent in the early 1990s to 2
percent by the early 2000s [13]. This was in the setting of stable or decreasing mortality
during the same time period.

Among term and late preterm infants, the prevalence of CP remained stable during the
1980s and 1990s [14]. An analysis of registry data from Europe and Australia found the
prevalence of CP declined in infants born from 1995 to 2015, perhaps due to improvements
in perinatal care [9].

SPECIFIC CAUSES AND RISK FACTORS

The etiology of CP is often multifactorial and can include anything with a negative impact on
the developing fetal or neonatal brain. Numerous antenatal and perinatal risk factors have
been reported ( table 1), though for many of these risk factors, a causal relationship has
not been established [3,10,15-21]. Potentially modifiable prenatal factors that may contribute
to CP risk include heavy maternal alcohol consumption, maternal smoking, maternal obesity,
and infections during pregnancy [21-28]. Prematurity is the most common association;
however, in many cases, no specific cause is identified [29].

The multifactorial etiology of CP was illustrated in a series of 213 children diagnosed with CP
in Australia, of whom 98 percent had contributing causes other than intrapartum hypoxia
[30]. The relative frequencies of different contributing factors were as follows (many children
had more than one contributing factor):

● Prematurity (78 percent)

● Intrauterine growth restriction (34 percent)
● Intrauterine infection (28 percent)
● Antepartum hemorrhage (27 percent)
● Severe placental pathology (21 percent)
● Multiple pregnancy (20 percent)

In a large case-control study using multivariable logistic regression modeling to identify pre-
and perinatal factors associated with increased risk of CP, the strongest independent
predictors were 5-minute Apgar score, maternal intrauterine infection, and maternal drug
use [21]. Other important predictors included maternal tobacco use, prolonged rupture of
membranes, maternal diabetes, preeclampsia, preterm birth, low birthweight, male sex, and
history of prior miscarriages. Infants with ≥2 of these risk factors were at substantially higher
risk.

Postnatal events may also be common contributing causes of CP. In a large epidemiological
study in Uganda, postnatal causes including cerebral malaria and seizures were attributed to
25 percent of CP cases [8].

Common causes of CP are described below. The associated causes and risk factors differ
somewhat based upon the subtype of CP ( table 2) [20].

Prematurity — The prevalence of CP is far higher in preterm compared with term infants.
CP develops in approximately 5 to 10 percent of surviving preterm very low birth weight
(VLBW; BW <1500 g) infants [2,31]. The risk of CP increases with decreasing gestational age
(GA) and birth weight (BW) [2]:

● GA:

• GA <28 weeks – 82 per 1000 live births

• GA 28 to 31 weeks – 43 per 1000 live births
• GA 32 to 36 weeks – 7 per 1000 live births
• GA >36 weeks – 1.4 per 1000 live births

● BW:
 • <1500 g – 59 per 1000 live births
• 1500 to 2499 g – 10 per 1000 live births
• >2500 g – 1.3 per 1000 live births

In preterm infants, CP is often associated with the following conditions [32]:

● Periventricular leukomalacia (PVL) – PVL refers to injury of cerebral white matter that
occurs in a characteristic distribution affecting white matter tracts responsible for leg
motor control more so than tracts controlling the arms. PVL consists of periventricular
focal necrosis, with subsequent cystic formation, and more diffuse cerebral white
matter injury. PVL is the major form of brain white matter injury that affects premature
infants. (See "Germinal matrix and intraventricular hemorrhage (GMH-IVH) in the
newborn: Risk factors, clinical features, screening, and diagnosis", section on 'White
matter injury'.)

● Intraventricular hemorrhage (IVH) – Severe IVH, periventricular hemorrhagic

infarction, and posthemorrhagic hydrocephalus (a potential complication of IVH) may
lead to CP [33]. (See "Germinal matrix and intraventricular hemorrhage (GMH-IVH) in
the newborn: Risk factors, clinical features, screening, and diagnosis" and "Germinal
matrix and intraventricular hemorrhage (GMH-IVH) in the newborn: Management and
outcome".)

● Bronchopulmonary dysplasia (BPD) – The risk of motor impairment is greater in

preterm infants affected by BPD [34]. The mechanism is not known but may involve the
use of corticosteroids to improve lung disease. This issue is discussed in greater detail
separately. (See "Postnatal use of glucocorticoids for prevention of bronchopulmonary
dysplasia (BPD) in preterm infants" and "Bronchopulmonary dysplasia (BPD):
Management and outcome", section on 'Neurodevelopmental outcomes'.)

Perinatal hypoxic-ischemic injury — Perinatal hypoxia and/or ischemia accounts for a

minority of cases of CP [35,36]. Reports of the proportion of CP cases caused by birth
asphyxia vary from <3 to >50 percent depending on the definition of birth asphyxia used
[35]. In a study using the criteria set forth by the American College of Obstetricians and
Gynecologists (ACOG) and the International Cerebral Palsy Task Force ( table 3), an acute
intrapartum hypoxic event was identified in only 1 percent (2 of 213 infants) of children with
CP [30,37]. (See "Etiology and pathogenesis of neonatal encephalopathy", section on 'Acute
events'.)

When severely damaging perinatal hypoxia occurs, it presents as neonatal encephalopathy,

which is a heterogeneous, clinically defined syndrome characterized by disturbed neurologic
function in the earliest days of life in an infant born at term, manifested by a subnormal level
of consciousness or seizures, often accompanied by difficulty with initiating and maintaining
respiration and depression of tone and reflexes [37]. (See "Clinical features, diagnosis, and
treatment of neonatal encephalopathy".)

Neonates with severe intrapartum hypoxia-ischemia may have seizures, encephalopathy,

hypotonia, dysfunction of other organ systems, a persistently low Apgar score, and evidence
of profound metabolic acidosis. On magnetic resonance imaging (MRI), the two most typical
patterns of hypoxic-ischemic injury are basal ganglia/thalamic-predominant pattern and a
watershed-predominant pattern ( image 1) [38].

Antenatal infection or injury

● Intrauterine infection – Congenital infections with organisms such as

cytomegalovirus, syphilis, Zika virus, varicella virus, and toxoplasmosis are associated
with increased risk of CP [39]. Bacterial infections are also associated with CP. (See
"Overview of TORCH infections" and "Congenital cytomegalovirus (cCMV) infection:
Clinical features and diagnosis" and "Congenital Zika virus infection: Clinical features,
evaluation, and management of the neonate" and "Clinical features, evaluation, and
diagnosis of sepsis in term and late preterm neonates".)

Maternal intraamniotic infection (IAI; also called clinical chorioamnionitis) is associated

with an increased risk of CP in the offspring [40-43]. A meta-analysis of 12 observational
studies demonstrated a strong association between IAI and cerebral palsy (pooled odds
ratio [OR] 2.42, 95% CI 1.5-3.8) [40]. Another case-control study found that any maternal
infection during pregnancy was associated with increased risk of CP (OR 2.9, 95% CI 1.7-
4.8) and that neonatal infection was a strong independent predictor of CP (OR 14.7, 95%
CI 1.7-126.5) [44]. (See "Clinical chorioamnionitis", section on 'Perinatal outcome'.)

In preterm infants, perinatal infection appears to play a key role in the pathogenesis of
cystic encephalomalacia, PVL, and subsequent CP [45]. (See 'Prematurity' above.)

● Maternal trauma during pregnancy – Severe trauma during pregnancy can have
adverse effects on the developing fetus and may increase the risk of long-term
disabilities, including CP. In a population-based longitudinal cohort study that included
>2,000,000 children, those with in utero exposure to maternal injury that required
emergency department or inpatient care had a higher prevalence of CP compared with
unexposed children (3.6 versus 2.5 per 1000 children) [46]. Maternal injuries of greater
severity (eg, those resulting in hospitalization) were associated with higher CP risk in
the offspring. The association remained statistically significant after adjusting for
maternal sociodemographic and clinical characteristics (hazard ratio 1.33, 95% CI 1.18-
1.50). These findings highlight the importance of prevention efforts to reduce the risk
of severe injury during pregnancy (eg, correct use of seat belts and airbags). (See
 "Prenatal care: Patient education, health promotion, and safety of commonly used
drugs", section on 'Use of seat belts and air bags'.)

Congenital abnormalities — Congenital abnormalities, both structural central nervous

system (CNS) abnormalities and abnormalities outside of the CNS, are more common in
children with than without CP [15,47-51]. Congenital abnormalities are noted in
approximately 15 percent of children with CP and are more common in term than preterm
infants [15,50]. In one registry study, the most common CNS anomalies were microcephaly
and congenital hydrocephalus [50]. Non-CNS anomalies included cardiac, urinary, and
skeletal malformations.

Intrapartum events may be influenced by a preexisting abnormality [52,53]. In one report,

congenital anomalies (mostly non-CNS anomalies) occurred more often in term infants with
neonatal encephalopathy than in controls (28 versus 4 percent) [54]. The congenital anomaly
was considered the cause of the encephalopathy in approximately one-third of affected
infants. Infants with congenital anomalies who had encephalopathy were three times more
likely to have CP than those without.

In children with CP due to brain malformations, the biologic basis is usually unknown. Some
result from abnormalities that occur during brain development and affect cell proliferation,
migration, differentiation, survival, or synaptogenesis. Disorders of development
occasionally result from exposure to radiation, toxins, or infectious agents during a critical
period of gestation [55-58]. Some disorders (eg, schizencephaly) are genetic and follow
Mendelian inheritance patterns [59-63]. Certain cerebral malformations can also be
associated with chromosomal abnormalities (eg, holoprosencephaly is associated with both
trisomy 13 and 18). Some neurocutaneous syndromes are associated with brain
malformations (eg, hemimegalencephaly and hypomelanosis of Ito or the linear sebaceous
nevus syndrome) [64]. (See "Prenatal diagnosis of CNS anomalies other than neural tube
defects and ventriculomegaly", section on 'Schizencephaly' and "Prenatal diagnosis of CNS
anomalies other than neural tube defects and ventriculomegaly", section on
'Holoprosencephaly' and "Congenital cytogenetic abnormalities", section on 'Trisomy 13
syndrome' and "Congenital cytogenetic abnormalities", section on 'Trisomy 18 syndrome'
and "The genodermatoses: An overview", section on 'Neurocutaneous syndromes'.)

Genetic susceptibility — A genetic contribution to CP risk was identified by the aggregation

of CP in groups with high consanguinity and observations of increased familial risk for CP
[65-67]. These disorders were historically thought to be uncommon causes of CP, but with
the advent of next-generation genetic testing techniques, they are increasingly recognized as
playing an important role in the etiology of CP [68-70]. Genetic factors have been identified
in 8 to higher than 30 percent of people with CP [71-77]. In a meta-analysis of 13 studies that
included more than 2600 patients with CP who underwent exome or genome testing, the
diagnostic yield was 31 percent [78]. In a report of 1345 children with CP (mean age 8.8
years) who were referred for diagnostic exome sequencing at one clinical genetics
laboratory, 33 percent were found to have pathogenic or likely pathogenic variants involving
>200 distinct genes [76]. The genes most frequently identified were CTNNB1 (n = 18),
KIF1A (n = 8), COL4A1 (n = 7), GNAO1 (n = 7), KCNQ2 (n = 7), and STXBP1 (n =
7). The diagnostic yield was highest when testing was performed concurrently in the
proband and both parents (ie, trio testing). Among trios with positive diagnostic results (n =
357), 72 percent had de novo variants, 20 percent were inherited in an autosomal recessive
manner, 5 percent were inherited in an autosomal dominant manner, and 3 percent were X-
linked.

Several genetic polymorphisms have been reported to be associated with susceptibility for
CP, including apolipoprotein E [79,80], genes associated with thrombophilia (eg, prothrombin
G20210A pathologic variant) [81,82], and genes involved with inflammation (eg, inducible
nitric oxide synthetase, lymphotoxin alpha, and certain cytokines) [83,84]. However, only the
association with prothrombin G20210A pathologic variant was confirmed by a subsequent
large study [82]. (See "Prothrombin G20210A".)

However, identifying a genetic cause of CP generally does not replace the diagnosis of CP
since some patients with a genetic disorder may have CP due instead or additionally to other
causes [85]. Up to 11 percent of those with acquired risk factors for CP have additional
genetic findings that may have contributed to their CP phenotype [68,69].

In addition, numerous genetic disorders can present with findings consistent with CP
( table 4). Some inborn errors of metabolism and other progressive disorders may initially
mimic CP [86,87]. Genetic testing can sometimes identify these conditions, some of which
may be potentially treatable. (See "Inborn errors of metabolism: Epidemiology,
pathogenesis, and clinical features".)

Hereditary spastic paraplegia (HSP), a mimicker of spastic diplegic CP, is a diverse group of
neurologic disorders that range in phenotype and inheritance pattern [88,89]. HSP is
characterized by progressive lower extremity spasticity; however, progression may be slow,
particularly in infantile-onset HSP, making it difficult to distinguish HSP from CP clinically.
Corresponding genes that have been linked to HSP are summarized in the table ( table 5).
HSP is discussed in greater detail separately. (See "Hereditary spastic paraplegia".)

Multiple births — The risk of CP is increased among multiple births [90-95]. Causes that may
contribute to this risk include low BW, prematurity, congenital anomalies, cord
entanglement, and abnormal vascular connections [96]. In a study of births in Western
Australia from 1980 to 1989, the prevalence of CP was 1.6, 7.3, and 28 per 1000 survivors to
one year of age in singletons, twins, and triplets, respectively [90]. In this report, the
increased rates of CP in multiples were limited to infants of normal BW, although multiples
were more likely to have low BW.

Death of a co-twin greatly increases the risk of CP. In the report from Western Australia, the
risk of CP among twins was greater when one twin died in utero (96 versus 12 per 1000 twin
pairs) compared with both surviving [90]. The mechanism may include release of
thromboplastin and emboli from the dead twin, causing injury to the survivor. It is possible
that some cases of CP in apparent singletons may be due to an unrecognized fetal death of a
co-twin [97].

Postnatal death also increases the risk of CP in the surviving co-twin, and monozygosity
appears to influence this risk. In a study that analyzed birth and death certificate data (1993
to 1995) for different sex (dizygotic) and same sex (dizygotic and monozygotic) twins, and
assessed disability in surviving twins after neonatal death of the co-twin using
questionnaires sent to clinicians, the risk of CP was greater in same-sex compared with
different-sex twin survivors (167 versus 21 per 1000) for infants of BW 1000 to 1999 g,
although the difference was only marginal for infants of BW <1000 g (224 versus 200 per
1000) [98].

Stroke — Stroke in the perinatal period contributes to CP, especially unilateral spasticity [99].
Thromboembolism and prothrombotic disorders contribute to the etiology of this disorder.
Lesions typically are identified by cranial imaging studies following a neonatal seizure.
However, some newborns with stroke appear asymptomatic until hemiparesis or other
abnormalities become more apparent as developmental milestones are assessed over time.
(See "Cerebral palsy: Classification and clinical features", section on 'Early signs of cerebral
palsy'.)

Prenatal causes include hypercoagulable states, vasculopathies, abnormal development of

blood vessels, and emboli secondary to disorders affecting the placenta or fetus [100]. Stroke
that occurs during early infancy may be caused by sepsis, disseminated intravascular
coagulation, venous sinus thrombosis, emboli, and congenital heart disease [101,102]. Some
cases are caused by periventricular atrophy or cerebral dysgenesis. Affected patients with
nondiagnostic neuroimaging may have maldevelopment at a microscopic level [103,104].
However, risk factors for stroke in the neonatal period are unique, and detailed vasculopathy
and hypercoagulability evaluations do not predict risk of recurrence [105]. (See "Stroke in the
newborn: Classification, manifestations, and diagnosis".)

Intracranial hemorrhage — Intracranial hemorrhage (ICH) in term infants is unusual but

frequently results in neuromotor abnormalities. Most are recognized because of the sudden
and dramatic onset of symptoms, including seizures, abnormal movements, apnea, lethargy,
irritability, vomiting, and bulging fontanelle. Diagnosis is made by cranial imaging.
The incidence depends in part upon the method of ascertainment. In one series of 33 term
infants with symptomatic ICH, the regional incidence was estimated to be 0.27 per 1000 live
births [106]. Approximately one-third of cases were related to coagulopathies. In another
report, ICH was diagnosed by ultrasound scan in 54 of 2019 term infants (2.7 percent)
treated in a newborn intensive care unit from 1989 to 1999 [107]. Neurologic impairment
developed in 28 percent.

Thalamic hemorrhage with residual germinal matrix hemorrhage is a common source of ICH
in this population. When no source is apparent, the ICH is thought to originate from the
choroid plexus. In one report, thalamic hemorrhage was identified in 12 of 19 term infants
younger than one month of age with ICH diagnosed by computed tomography (CT) [108].
Thalamic hemorrhage typically occurred in infants with uneventful birth histories and
presentation after one week of age. Many had predisposing factors for cerebral vein
thrombosis (eg, sepsis, congenital heart disease, coagulopathy, electrolyte disturbance). At
18 months of age, the majority had CP, predominantly hemiplegia, and other neurologic
abnormalities such as hydrocephalus and seizures.

Acquired postnatal causes — Though CP is most commonly due to prenatal or perinatal

factors, it can also result from insults to the developing brain acquired during infancy and
early childhood, typically after one month of age up to two years old [109]. Approximately 10
to 25 percent of cases of CP are acquired after the neonatal period. Postnatal causes of CP
may be more common globally. Most of these patients have spastic CP. Common causes of
postnatally acquired CP include:

● Stroke − Stroke is uncommon in infants and children and is usually associated with an
underlying disorder (eg, congenital heart disease, prothrombotic disorder, sickle cell
disease, vasculopathy, or metabolic disorder). Stroke typically results in unilateral
spasticity. (See "Stroke in the newborn: Classification, manifestations, and diagnosis"
and "Ischemic stroke in children and young adults: Epidemiology, etiology, and risk
factors".)

● Trauma − (See "Child abuse: Evaluation and diagnosis of abusive head trauma in
infants and children".)

● Severe hypoxic events such as near-drowning − (See "Drowning (submersion

injuries)", section on 'Neurologic'.)

● Sepsis or meningitis − (See "Clinical features, evaluation, and diagnosis of sepsis in

term and late preterm neonates" and "Bacterial meningitis in the neonate: Neurologic
complications".)

● Kernicterus − Infants with severe hyperbilirubinemia are at risk for kernicterus,

permanent neurologic sequelae of bilirubin-induced neurotoxicity that manifests itself
 as a type of CP characterized by choreoathetosis, with gaze abnormalities and
sensorineural hearing loss. The disorder results when unconjugated bilirubin enters the
brain and causes focal necrosis of neurons and glia. The regions most often affected
include the basal ganglia and the brainstem nuclei for oculomotor and auditory
function, accounting for the clinical features of this condition. (See "Unconjugated
hyperbilirubinemia in neonates: Risk factors, clinical manifestations, and neurologic
complications", section on 'Chronic bilirubin encephalopathy (kernicterus)'.)

● Other causes of encephalopathy − (See "Etiology and pathogenesis of neonatal

encephalopathy" and "Acute toxic-metabolic encephalopathy in children", section on
'Specific etiologies of encephalopathy'.)

PREVENTION

Antenatal measures — Antenatal measures to reduce the likelihood of CP include provision

of routine prenatal care, including measures to reduce the likelihood of preterm birth. These
issues are discussed separately. (See "Prenatal care: Initial assessment" and "Prenatal care:
Second and third trimesters" and "Spontaneous preterm birth: Overview of risk factors and
prognosis".)

Magnesium sulfate — There is evidence from clinical trials that antenatal administration of
magnesium sulfate to females at risk for preterm birth decreases the incidence and severity
of CP in their offspring without affecting mortality. This issue is discussed in greater detail
separately. (See "Neuroprotective effects of in utero exposure to magnesium sulfate".)

Intrapartum measures — In vigorous preterm infants, delaying umbilical cord clamping for
at least 30 seconds after birth may reduce the risk of intraventricular hemorrhage. This issue
is discussed in greater detail separately. (See "Labor and delivery: Management of the
normal third stage after vaginal birth", section on 'Delayed cord clamping'.)

Postnatal measures

Supportive measures — Supportive, neuroprotective measures for neonates at risk of

neurologic injury (ie, preterm very low birth weight [VLBW] infants and infants with neonatal
asphyxia and/or encephalopathy) are aimed at reducing the likelihood of long-term
neurodevelopmental sequelae and include:

● Maintaining adequate ventilation (see "Overview of mechanical ventilation in

neonates")

● Maintaining sufficient cerebral perfusion (see "Neonatal shock: Etiology, clinical

manifestations, and evaluation")
 ● Maintaining normal metabolic status (see "Fluid and electrolyte therapy in newborns"
and "Management and outcome of neonatal hypoglycemia" and "Neonatal
hyperglycemia", section on 'Management')

● Controlling seizures (see "Treatment of neonatal seizures")

● Treating any underlying causes for encephalopathy (eg, infection or metabolic

derangements) (see "Management and outcome of sepsis in term and late preterm
neonates" and "Treatment and prevention of bacterial sepsis in preterm infants <34
weeks gestation" and "Metabolic emergencies in suspected inborn errors of
metabolism: Presentation, evaluation, and management")

Therapeutic hypothermia — For infants with neonatal asphyxia and/or encephalopathy,

therapeutic hypothermia improves survival and neurodevelopmental outcome at 18 months.

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Cerebral palsy".)

SUMMARY AND RECOMMENDATIONS

● Epidemiology – The prevalence of cerebral palsy (CP) is approximately 2 to 3.4 cases

per 1000 children. The risk is markedly increased among preterm infants with low birth
weight (BW). (See 'Epidemiology' above.)

● Etiology – The etiology of CP is multifactorial ( table 1). In many cases, CP is thought

to be due to prenatal factors. (See 'Specific causes and risk factors' above.)

• Prematurity and/or low BW are the most commonly identified prenatal risk factors
for CP. CP develops in approximately 5 to 15 percent of surviving very low birth
weight (VLBW) infants. In this population, CP is often associated with the
periventricular leukomalacia (PVL), intraventricular hemorrhage (IVH), and/or
bronchopulmonary dysplasia (BPD). (See 'Prematurity' above.)

• Perinatal hypoxia and/or ischemia likely accounts for a minority of cases of CP.
Infants with CP caused by an acute intrapartum hypoxic-ischemic event are more
likely to have spastic quadriparesis or dyskinetic CP than other CP subtypes. (See
'Perinatal hypoxic-ischemic injury' above.)

• Intrauterine infections and maternal trauma during pregnancy are risk factors for
CP. Congenital infections associated with CP include bacterial infections,
 cytomegalovirus, syphilis, Zika virus, varicella virus, and toxoplasmosis. (See
'Antenatal infection or injury' above.)

• Genetic causes may account for up to one-third of all cases of CP. Numerous genetic
disorders can present with findings of CP ( table 4). (See 'Genetic susceptibility'
above.)

• Multiple births are associated with an increased risk of CP due to associated risks of
low BW, prematurity, congenital anomalies, cord entanglement, and abnormal
vascular connections. (See 'Multiple births' above.)

• Stroke in the perinatal period may cause CP and is typically manifested as unilateral
spasticity. (See 'Stroke' above and 'Intracranial hemorrhage' above and "Stroke in
the newborn: Classification, manifestations, and diagnosis".)

• Insults to the developing brain acquired during infancy and early childhood may
cause CP. These include stroke, traumatic or hypoxic injury, sepsis, kernicterus, and
other sources of encephalopathy in children. (See 'Acquired postnatal causes'
above.)

● Prevention – Preventive measures to reduce the likelihood of CP include (see

'Prevention' above):

• Antenatal measures – Provision of routine prenatal care, including measures to

reduce the likelihood of preterm birth (see "Prenatal care: Initial assessment" and
"Prenatal care: Second and third trimesters" and "Spontaneous preterm birth:
Overview of risk factors and prognosis")

Antenatal administration of magnesium sulfate for females at risk for preterm

delivery is discussed separately. (See "Neuroprotective effects of in utero exposure
to magnesium sulfate".)

• Intrapartum measures – In vigorous preterm infants, delaying umbilical cord

clamping for at least 30 seconds after birth may reduce the risk of IVH. This issue is
discussed separately. (See "Labor and delivery: Management of the normal third
stage after vaginal birth", section on 'Delayed cord clamping'.)

• Postnatal measures – Supportive neuroprotective measures for neonates at risk of

neurologic injury (ie, preterm VLBW infants and infants with neonatal asphyxia
and/or encephalopathy)

Therapeutic hypothermia for infants with neonatal asphyxia and/or encephalopathy

ACKNOWLEDGMENTS

The UpToDate editorial staff acknowledges Geoffrey Miller, MD and Laurie Glader, MD, who
contributed to earlier versions of this topic review.

Use of UpToDate is subject to the Terms of Use.

Topic 6173 Version 57.0

GRAPHICS

Prenatal and perinatal factors associated with an increased risk of cerebral

palsy*

Estimated risk ¶
Prematurity

GA <28 weeks OR 60.9, 95% CI 34.3-108.0

GA 28 to 31 weeks OR 32.0, 95% CI 20.6-49.5

GA 32 to 36 weeks OR 5.0, 95% CI 2.9-8.6

Low birth weight

<1500 g OR 44.5, 95% CI 35.6-55.5

1500 to 2499 g OR 7.6, 95% CI 6.0-9.7

Intrauterine infection

Any maternal infection during pregnancy RR 2.5, 95% CI 1.9-3.2

Maternal chorioamnionitis RR 2.9, 95% CI 2.0-4.2

Preeclampsia OR 1.9, 95% CI 1.5-2.5

Placental abruption OR 10.9, 95% CI 8.4-14.1

Multiple pregnancy OR 3.7, 95% CI 3.0-4.5

Heavy maternal alcohol consumption OR 3.3, 95% CI 1.3-8.5

Maternal smoking HR 1.8, 95% CI 1.1-2.9

Maternal trauma during pregnancy HR 1.33, 95% CI 1.18-1.50

Maternal obesity (prepregnancy BMI ≥30) RR 1.6, 95% CI 1.1-2.2

Small size for gestational age OR 3.7, 95% CI 3.1-4.4

Other congenital abnormalities OR 5.2, 95% CI 2.8-9.7

Apgar <7 at 5 minutes OR 27.0, 95% CI 23.5-31.2

Neonatal infection OR 14.7, 95% CI 1.7-126.5

Respiratory distress syndrome HR 2.1, 95% CI 1.4-3.1

Requiring mechanical ventilation after birth OR 2.4, 95% CI 2.4-4.5

Requiring antibiotic therapy after birth OR 1.7, 95% CI 1.3-2.2

Neonatal seizures OR 7.4, 95% CI 4.8-11.6

GA: gestational age; OR: odds ratio; RR: relative risk; HR: hazard ratio; BMI: body mass index; CP:
cerebral palsy.

* This table summarizes prenatal and perinatal factors that have been reported to be associated with
an increased risk of CP. Studies have identified associations with these factors and CP; however, in
most cases, a causal relationship has not been established. While the estimated risks associated with
individual factors are presented, in many cases, CP is multifactorial and multiple risk factors coexist. In
most studies, prematurity and low birth weight are the strongest and most consistent predictors of
CP.

¶ Baseline risk of CP is approximately 0.2%.

References:
1. Hirvonen M, Ojala R, Korhonen P, et al. Cerebral palsy among children born moderately and late preterm. Pediatrics
2014; 134:e1584.
2. Hjern A, Thorngren-Jerneck K. Perinatal complications and socio-economic differences in cerebral palsy in Sweden - a
national cohort study. BMC Pediatr 2008; 8:49.
3. O'Leary CM, Watson L, D'Antoine H, et al. Heavy maternal alcohol consumption and cerebral palsy in the offspring. Dev
Med Child Neurol 2012; 54:224.
4. Streja E, Miller JE, Bech BH, et al. Congenital cerebral palsy and prenatal exposure to self-reported maternal infections,
fever, or smoking. Am J Obstet Gynecol 2013; 209:332.e1.
5. Croen LA, Grether JK, Curry CJ, Nelson KB. Congenital abnormalities among children with cerebral palsy: More evidence
for prenatal antecedents. J Pediatr 2001; 138:804.
6. Ahlin K, Himmelmann K, Hagberg G, et al. Cerebral palsy and perinatal infection in children born at term. Obstet
Gynecol 2013; 122:41.
7. Ayubi E, Sarhadi S, Mansori K. Maternal infection during pregnancy and risk of cerebral palsy in children: A systematic
review and meta-analysis. J Child Neurol 2021; 36:385.
8. Thygesen SK, Olsen M, Østergaard JR, Sørensen HT. Respiratory distress syndrome in moderately late and late preterm
infants and risk of cerebral palsy: a population-based cohort study. BMJ Open 2016; 6:e011643.
9. Forthun I, Wilcox AJ, Strandberg-Larsen K, et al. Maternal Prepregnancy BMI and Risk of Cerebral Palsy in Offspring.
Pediatrics 2016; 138.
10. Ahmed A, Rosella LC, Oskoui M, et al. In Utero Exposure to Maternal Injury and the Associated Risk of Cerebral Palsy.
JAMA Pediatr 2023; 177:53.

Graphic 102940 Version 7.0

Causes and clinical features of cerebral palsy subtypes

Proportion Common clin

Infants
of CP Common causes
affected Infants and
cases young children

Spastic
subtypes

Spastic 13 to 25% Most commonly Preterm First few months

diplegia * associated with infants – Hypotonia of
PVL Risk increases the lower limbs
with with delayed
decreasing functional
gestational maturation
age By 6 months –
Spasticity
involving ankle
plantar flexors
and hip
adductors
Crawling may be
combat style

Spastic 21 to 40% Neonatal stroke Term infants Motor

hemiplegia * Prenatal of normal asymmetry (may
circulatory birth weight not be apparent
disturbances
Brain in the newborn
maldevelopment period)
Early (before age
12 months) hand
dominance
Inability to use
both hands in
midline or to
reach out with
the affected limb
Abnormal
posturing on one
side
In prone
position, the
affected upper
limb provides
decreased
support, and
movement of the
affected leg is
diminished
In a sitting
position, the
affected leg
tends to extend
Protective
reactions that
appear at 5 to 8
months of age
are asymmetric
Over first 1 to 2
years, movement
and tone on the
affected side
typically
decrease before
tone and tendon
reflexes
abnormally
increase
Typical posture
(refer to
description to
the right)
appears by age 2
years in most
cases
 Spastic 20 to 43% Congenital Most Moderate or
quadriplegia * infection commonly severe
Cerebral term SGA psychomotor
dysgenesis infants, but delay
Perinatal or can also occur Poor head
postnatal events in preterm control
infants Spasticity may
begin by 2 to 3
months of age
Adduction of the
thighs results in
typical scissoring
of the legs
By 9 to 10
months of age,
infants when
pulled to sitting
are unable to flex
the legs and
have poor
truncal balance

Dyskinetic 12 to 14% Most cases are Predominantly In early infancy:

subtypes caused by severe term infants Reduced
perinatal asphyxia spontaneous
resulting in injury movement
to the thalamus, Hypotonia at
basal ganglia, rest, variable
hippocampus, tone with
reticular movement or
formation, and/or emotion
cerebellum Oromotor
Severe incoordination
hyperbilirubinemia Persistence of
(kernicterus) can primitive
cause reflexes
choreoathetotic CP
Involuntary
grimacing
Drooling
Delayed
psychomotor
development
Head can be
persistently
turned

Age 2 to 3 years:
Involuntary
movements
are apparent
Abnormal
posturing:
Extension
patterns in
the supine
position
Flexion
with
shoulder
retraction
in the
prone
position
Head
usually is
persistently
turned to
one side
 Ataxic CP 4 to 13% Most cases are Term infants Hypotonia ¶ and
caused by early incoordination
prenatal events Motor
Etiology is milestones and
frequently language skills
unknown typically are
Some cases have delayed
genetic causes,
including:
Cerebellar
hypoplasia
Granule cell
deficiency
Joubert
syndrome
Rarely associated
with congenital
hypoplasia of the
cerebellum

CP: cerebral palsy; PVL: periventricular leukomalacia; SGA: small for gestational age.

* The suffix "paresis" denotes weakness and "plegia" means paralysis. However, these terms often are
used interchangeably and do not necessarily imply a difference in severity.

¶ A separate category of "hypotonic CP" (also called "atonic CP") has been described, though it is
generally absent from contemporary classifications. The majority of patients with "hypotonic CP" in
early infancy later develop spastic, dyskinetic, and particularly ataxic CP.
References:
1. Surveillance of Cerebral Palsy in Europe. Surveillance of cerebral palsy in Europe: a collaboration of cerebral palsy
surveys and registers. Surveillance of Cerebral Palsy in Europe (SCPE). Dev Med Child Neurol 2000; 42:816.
2. Noritz GH, Murphy NA, Neuromotor Screening Expert Panel. Motor delays: early identification and evaluation.
Pediatrics 2013; 131:e2016.
3. Odding E, Roebroeck ME, Stam HJ. The epidemiology of cerebral palsy: incidence, impairments and risk factors. Disabil
Rehabil 2006; 28:183.

Graphic 74533 Version 12.0

Markers of an acute peripartum or intrapartum hypoxic-ischemic event

Neonatal signs consistent with an acute peripartum or intrapartum event:

Apgar score of <5 at 5 minutes and 10 minutes

Fetal umbilical artery acidemia – Fetal umbilical artery pH <7.0, or base deficit ≥12 mmol/L, or
both
Neuroimaging evidence of acute brain injury seen on brain MRI or MRS consistent with hypoxia-
ischemia
Presence of multisystem organ failure consistent with hypoxic-ischemic encephalopathy

Type and timing of contributing factors that are consistent with an acute peripartum
or intrapartum event:

A sentinel hypoxic or ischemic event occurring immediately before or during labor and delivery:
Ruptured uterus
Severe abruptio placentae
Umbilical cord prolapse
Amniotic fluid embolus with coincident severe and prolonged maternal hypotension and
hypoxemia
Maternal cardiovascular collapse
Fetal exsanguination from either vasa previa or massive fetomaternal hemorrhage
Fetal heart rate monitor patterns consistent with an acute peripartum or intrapartum event,
particularly a category I fetal heart rate pattern on presentation that converts to one of the
following patterns:
Category III pattern
Tachycardia with recurrent decelerations
Persistent minimal variability with recurrent decelerations
Timing and type of brain injury patterns based on imaging studies consistent with an etiology of
an acute peripartum or intrapartum event. Well-defined patterns on brain MRI typical of hypoxic-
ischemic cerebral injury in the newborn are:
Deep nuclear gray matter (ie, basal ganglia or thalamus) injury
Watershed (borderzone) cortical injury
No evidence of other proximal or distal factors that could be contributing

Developmental outcome is spastic quadriplegia or dyskinetic cerebral palsy:

Other subtypes of cerebral palsy are less likely to be associated with acute intrapartum hypoxic-
ischemic events
Other developmental abnormalities may occur, but they are not specific to acute intrapartum
hypoxic-ischemic encephalopathy and may arise from a variety of other causes

MRI: magnetic resonance imaging; MRS: magnetic resonance spectroscopy.

Source: Neonatal encephalopathy and neurologic outcome, second edition. Report of the American College of Obstetricians
and Gynecologists' Task Force on Neonatal Encephalopathy. Obstet Gynecol 2014; 123:896.
Graphic 96192 Version 2.0
Patterns of brain injury on MRI in neonates with hypoxic-ischemic
encephalopathy

Patterns of brain injury in neonates with hypoxic-ischemic encephalopathy on T1-weighted, T2-

weighted, and DWI.

MRI: magnetic resonance imaging; DWI: diffusion-weighted images; BGT: basal ganglia/thalamic-
predominant injury; WS: watershed with cortical laminar necrosis and subcortical white matter injury;
Global: global pattern with total cerebral injury.

Reproduced from: Massaro AN. MRI for neurodevelopmental prognostication in the high-risk term infant. Semin Perinatol
2015; 39:159. Illustration used with the permission of Elsevier Inc. All rights reserved.

Graphic 100474 Version 3.0

Genetic and metabolic disorders that may present with motor symptoms
resembling cerebral palsy

Type of Clinical and

Laboratory and
motor radiographic
diagnostic tests
disturbance features

Organic acidemias

Glutaric aciduria type 1 Dystonia Episodes of Abnormal urinary

metabolic organic acid analysis
decompensation and (elevated glutaric acid
encephalopathy and 3-hydroxyglutaric
often precipitated by acid)
infection and fever
Rarely presents in the
newborn period
Microencephalic
macrocephaly
Seizures
(approximately 20%)
Cognitive function is
preserved
MRI findings include
frontal and temporal
atrophy

Holocarboxylase Hypotonia Ketoacidosis Abnormal urinary

synthetase deficiency Dermatitis organic acid analysis
Alopecia (elevated beta-
hydroxyisovalerate,
Seizures
beta-
Developmental delay
methylcrotonylglycine
beta-
hydroxypropionate,
methylcitrate, and
tiglylglycine)

Urea cycle disorders

Arginase deficiency Spasticity Hyperammonemia Elevated ammonia

Encephalopathy level
Respiratory alkalosis Abnormal quantitative
plasma amino acid
analysis (elevated
arginine level)

Disorders of carbohydrate metabolism

 Pyruvate Spasticity Lactic acidosis Elevated lactate and
dehydrogenase Seizures pyruvate levels in
Ataxia
deficiency blood and CSF
Intellectual disability
Hypotonia
Abnormal PDH
enzymatic activity in
cultured fibroblasts

Peroxisomal disorders

Zellweger syndrome Hypotonia Craniofacial Elevated plasma VLCFA

dysmorphism levels
Hepatomegaly Elevated levels of
Neonatal seizures phytanic acid, pristani
Profound acid, and pipecolic
developmental delay acid in plasma and
fibroblasts
MRI findings include
cortical and white Reduced plasmalogen
matter abnormalities in erythrocytes

Neurologic Molecular genetic

deterioration is rapid testing for variants in
and infants rarely the PEX1 or PEX6
survive beyond six genes may also be
months of age helpful

Adrenoleukodystrophy Spasticity Clinical features vary Elevated plasma VLCFA

and by specific type, and levels
adrenomyeloneuropathy may include: Molecular genetic
Cognitive and testing for variants in
behavioral the ABCD1 gene may
abnormalities be helpful in cases
Adrenal with borderline VLCFA
insufficiency levels or atypical
Hyperpigmented features, or in females
skin
Gonadal
dysfunction
Neurologic
deterioration
progresses at a
variable rate

Infantile Refsum disease Hypotonia Abnormalities of the Elevated plasma VLCFA

Ataxia optic nerve and disc levels, though less
Retinitis pigmentosa pronounced than in
Sensorineural Zellweger syndrome
hearing loss and ALD

Hepatomegaly and
cirrhosis
 Neurologic
deterioration is
slower than in
Zellweger syndrome
or ALD

Lipid storage disorders

Niemann-Pick disease Ataxia Progressive Abnormal liver

type C neurodegeneration function tests
Dystonia
Hepatosplenomegaly Fibroblast cell culture
Systemic involvement with filipin staining
of liver, spleen, or
lung precedes
neurologic symptoms
MRI shows cerebral
and cerebellar
atrophy and thinning
of the corpus
callosum

Mitochondrial disorders

Leigh syndrome Ataxia Progressive Increased lactate

Dystonia psychomotor levels in blood and CS
regression Genetic testing for
Seizures specific variants (>20
External have been described)
ophthalmoplegia
Lactic acidosis
Vomiting
MRI shows abnormal
white matter signal
in the putamen,
basal ganglia, and
brainstem on T2
images

Others

Angelman syndrome Ataxia Profound intellectual Methylation studies

disability and chromosome
Postnatal microarray to detect
microcephaly chromosome 15
Typical abnormal anomalies and UBE3A
behaviors genetic variants
(paroxysmal laughter,
easily excitable)

Ataxia-telangiectasia Ataxia Progressive Elevated serum alpha-

cerebellar ataxia fetoprotein level
 Abnormal eye Low IgA and IgG levels
movements Lymphopenia
Oculocutaneous Genetic testing for
telangiectasias variants in the ATM
Immune deficiency gene
Increased risk of
malignancy

Congenital myotonic Hypotonia Facial diplegia Genetic testing for

dystrophy Arthrogryposis DMPK variants
Poor feeding Electromyography
Intellectual disability showing myotonic
discharges
Electrocardiography
may show cardiac
conduction
abnormalities

Dopa-responsive Focal dystonia Onset in early Positive response to a

dystonia childhood trial of levodopa
Spastic diplegia
Symptoms worsen
with fatigue and
exercise

Hereditary spastic Spastic Variable depending >50 genetic variants

paraplegia paraplegia on specific genetic have been identified
variant Genetic testing is
available for many

Lesch-Nyhan syndrome Choreoathetosis Self-mutilating Elevated uric acid leve

Dystonia behavior Abnormal enzymatic
Urinary stones due to activity of HPRT in
Spasticity
hyperuricemia cultured fibroblasts
Genetic testing for
HPRT variants

Metachromatic Hypotonia Regression of motor Deficient arylsulfatase

leukodystrophy skills A enzyme activity in
Ataxia
Seizures leukocytes or cultured
Optic atrophy skin fibroblasts

Reduced or absent
deep tendon reflexes
Intellectual disability
Miller-Dieker Hypotonia or Lissencephaly Cytogenetic testing fo
lissencephaly spasticity Microcephaly 17p13.3 microdeletion
Dysmorphic features
Seizures
Failure to thrive

Pelizaeus-Merzbacher Spasticity Nystagmus Genetic testing for

Ataxia Cognitive impairment variants in PLP1 gene
Onset in infancy
Athetosis
Slowly progressive
Language
development may be
normal
MRI shows white
matter abnormalities

Pontocerebellar Hypotonia Clinical features vary Genetic testing for

hypoplasias by specific type, and PCH gene variants
Dyskinesias
may include: (variants in >10 genes
Progressive have been described)
muscle atrophy
Microcephaly
Developmental
delay
MRI shows small
cerebellum and
brainstem
including the
pons

Rett syndrome Dystonia Occurs almost Clinical diagnosis

Spasticity exclusively in females Genetic testing for
Normal development MECP2 variants may
during first six be helpful
months followed by
regression and loss
of milestones
Loss of speech
capability
Stereotypic hand
movements
Seizures
Autistic features

Aicardi-Goutieres Spasticity Infantile spasms Lymphocytic

Dystonia Abnormal eye pleocytosis in CSF
movements Genetic testing for
Truncal hypotonia pathologic variants in
 Intellectual disability TREX1
MRI shows agenesis
of the corpus
callosum and
calcifications of the
basal ganglia and
periventricular areas

This list is not exhaustive. Refer to UpToDate topics on cerebral palsy for further details.

VLCFA: very long chain fatty acids; PDH: pyruvate dehydrogenase; HPRT: hypoxanthine
phosphoribosyltransferase; CSF: cerebrospinal fluid; PCH: pontocerebellar hypoplasias; MRI: magnetic
resonance imaging; Ig: immunoglobulin; ATM: ataxia-telangiectasia mutated; ALD:
adrenoleukodystrophy.

Graphic 102942 Version 3.0

Genetic forms of hereditary spastic paraplegia

Designation Locus Gene Predominant Inheritance OMIM

phenotype number
SPG1 Xq28 L1CAM Complicated X-linked 303350

SPG2 Xq22.2 PLP1 Complicated X-linked 312920

SPG3A 14q22.1 ATL1 Pure AD 182600

SPG4 2p22.3 SPAST Pure AD 182601

SPG5A 8q12.3 CYP7B1 Pure AR 270800

SPG6 15q11.2 NIPA1 Pure AD 600363

SPG7 16q24 SPG7 Pure or AR and AD 607259

complicated

SPG8 8q24.13 KIAA0196 Pure AD 603563

SPG9A 10q24.1 ALDH18A1 Complicated AD 601162

SPG9B 10q24.1 ALDH18A1 Complicated AR 616586

SPG10 12q13.3 KIF5A Pure AD 604187

SPG11 15q21.1 SPG11 Complicated AR 604360

SPG12 19q13.32 RTN2 Pure AD 604805

SPG13 2q33.1 HSPD1 Pure AD 605280

SPG14 3q27-q28 SPG14 Complicated AR 605229

SPG15 14q24.1 ZFYVE26 Complicated AR 270700

SPG16 Xq11.2 SPG16 Complicated X-linked 300266

SPG17 11q12.3 BSCL2 Complicated AD 270685

SPG18 8p1123 ERLIN2 Complicated AR 611225

SPG19 9q – Pure AD 607152

SPG20 13q13.3 SPG20 Complicated AR 275900

SPG21 15q22.31 ACP33 Complicated AR 248900

SPG23 1q32.1 DSTYK Complicated AR 270750

SPG24 13q14 SPG24 Pure AR 607584

SPG25 6q23-q24.1 SPG25 Complicated AR 608220

SPG26 12p11.1-q14 B4GALNT1 Complicated AR 609195

SPG27 10q22.1-q24.1 – Complicated AR 609041

SPG28 14q22.1 DDHD1 Pure AR 609340

SPG29 1p31.1-p21.1 – Complicated AD 609727

SPG30 2q37.3 KIF1A Pure AR 610357

SPG31 2p11 REEP1 Pure AD 609139

SPG32 14q12-q21 – Complicated AR 611252

SPG33 10q24.2 ZFYVE27 Pure AD 610244

SPG34 Xq24-q25 – Pure X-linked 300750

SPG35 16q23.1 FA2H Complicated AR 612319

SPG36 12q23-q24 – Complicated AD 613096

SPG37 8p21.1-q13.3 SPG37 Pure AD 611945

SPG38 4p16-p15 SPG38 Complicated AD 612335

SPG39 19p13.2 PNPLA6 Complicated AR 612020

SPG41 11p14.1-p11.2 SPG41 Pure AD 613364

SPG42 3q25.31 SLC33A1 Pure AD 612539

SPG43 19q12 C19ORF12 Complicated AR 615043

SPG44 1q42.13 GJC2 Complicated AR 613206

SPG45 10q24.3-q25.1 NT5C2 Complicated AR 613162

SPG46 9p13.3 GBA2 Complicated AR 614409

SPG47 1p13.2 AP4B1 Complicated AR 614066

SPG48 7p22.1 AP5Z1 Pure AR 613647

SPG49 14q32.31 TECPR2 Complicated AR 615031

SPG50 7q22.1 AP4M1 Complicated AR 612936

SPG51 15q21.2 AP4E1 Complicated AR 613744

SPG52 14q12 AP4S1 Complicated AR 614067

SPG53 8p22 VPS37A Complicated AR 614898

SPG54 8p11.23 DDHD2 Complicated AR 615033

SPG55 12q24.31 C12ORF65 Complicated AR 615035

SPG56 4q25 CYP2U1 Complicated AR 615030

SPG57 3q12.2 TFG Complicated AR 615658

SPG58 17p13.2 KIF1C Complicated AR and AD –

SPG61 16p12.3 ARL6IP1 Complicated AR 615685

SPG62 10q24.3 ERLIN1 Complicated AR 615681

SPG63 1p13.3 AMPD2 Complicated AR 615686

SPG64 10q24.1 ENTPD1 Complicated AR 615683

SPG72 5q31.2 REEP2 Pure AR/AD 615625

SPG73 19q13.33 CPT1C Pure AD 616282

 SPG74 1q42.1 IBA57 Complicated AR 616451

SPG75 19q13.1 MAG Complicated AR 616680

SPG76 11q13.1 CAPN1 Complicated AR 616907

SPG77 6p25.1 FARS2 Pure AR 617046

SPG78 1p36.1 ATP13A2 Complicated AR 617225

SPG79 4p13 UCHL1 Complicated AR 615491

SPG80 9p13.3 UBAP1 Pure AD 618418

SPG81 2p23.3 SELENOI Complicated AR 618768

SPG82 17q25.3 PCYT2 Complicated AR 618770

SPG83 1p34.1 HPDL Pure AR 618994

SPG84 22q11.21 PI4KA Complicated AR 619621

SPG85 8p11.21 RNF170 Complicated AR 619686

SPG86 6p21.33 ABHD16A Complicated AR 619735

SPG87 14q24.3 TMEM63C Pure or AR 619966

complicated

Data from Online Mendelian Inheritance in Man.

Graphic 95449 Version 8.0

