Pediatr Radiol (2015) 45 (Suppl 3):S485–S496

DOI 10.1007/s00247-015-3320-1

ADVANCES IN PEDIATRIC NEURORADIOLOGY

Skull base development and craniosynostosis

Susan I. Blaser & Nancy Padfield & David Chitayat &
Christopher R. Forrest

Received: 15 October 2014 / Revised: 14 November 2014 / Accepted: 15 February 2015

# Springer-Verlag Berlin Heidelberg 2015

Abstract Abnormal skull shape resulting in craniofacial de- craniosynostosis. Evidence for intracranial hypertension
formity is a relatively common clinical finding, with deformi- may be seen both pre- and postoperatively, associated
ty either positional (positional plagiocephaly) or related to with jugular foraminal stenosis, sinovenous occlusion,
premature ossification and fusion of the skull sutures (cranio- hydrocephalus and Chiari 1 malformations. Following
synostosis). Growth restriction occurring at a stenosed suture clinical assessment, imaging evaluation may include ra-
is associated with exaggerated growth at the open sutures, diographs, high-frequency US of the involved sutures,
resulting in fairly predictable craniofacial phenotypes in low-dose (20–30 mAs) CT with three-dimensional
single-suture non-syndromic pathologies. Multi-suture reformatted images, MRI and nuclear medicine brain
syndromic subtypes are not so easy to understand with- imaging. Anomalous or vigorous collateral venous
out imaging. Imaging is performed to define the site drainage may be mapped preoperatively with CT or
and extent of craniosynostosis, to determine the pres- MR venography or catheter angiography.
ence or absence of underlying brain anomalies, and to
evaluate both pre- and postoperative complications of
Keywords Craniosynostosis . Skull base . Craniofacial
deformity . Ultrasonography . Magnetic resonance imaging .
S. I. Blaser (*) : N. Padfield Radiography . Computed tomography . Children
Department of Diagnostic Imaging,
Division of Neuroradiology,
The Hospital for Sick Children and University of Toronto,
Toronto M5G 1X8, Canada
e-mail: [email protected] Introduction
S. I. Blaser
Craniosynostosis occurs in 1 in 2,500 live births. Most cases
Department of Otolaryngology — Head and Neck Surgery,
University of Toronto, Toronto, Canada of single-suture synostosis are likely caused by defective
dural-mesenchymal signaling issues and are thought to be
D. Chitayat idiopathic, although genetic causes are increasingly being
Division of Clinical and Metabolic Genetics,
The Hospital for Sick Children and University of Toronto,
identified. Multisuture synostoses are likely genetically influ-
Toronto, Canada enced, either by single gene disorders or chromosomal abnor-
malities. Metabolic (mucopolysaccharidoses, I-cell disease)
D. Chitayat causes of premature sutural fusion are extremely rare. Delay
Prenatal Diagnosis and Medical Genetics Program,
in fusion has been reported with hypothyroidism and equally
Mount Sinai Hospital and University of Toronto,
Toronto, Canada rare metabolic and genetic disorders like cleidocranial
dysostosis (RUNX2 mutation) and peroxisomal biogenesis
C. R. Forrest disorders (Zellweger). Iatrogenic factors are somewhat more
Centre for Craniofacial Care and Research,
Division of Plastic and Reconstructive Surgery,
common and include exposure to teratogens, early postnatal
The Hospital for Sick Children and University of Toronto, shunting of hydrocephalus and early craniofacial irradiation
Toronto, Canada for tumor control.
486 Pediatr Radiol (2015) 45 (Suppl 3):S485–S496

Normal cranial development involved in syndromic synostosis are FGFR1–3 (gain of func-
tion mutations in Pfeiffer, Crouzon, Apert and Muenke syn-
The neurocranium of the skull comprises the base, formed by dromes), TWIST1 (helix-loop-helix transcription factor found
endochondral ossification via formation of a cartilaginous in- in Saethre–Chotzen syndrome), MSX2 (both a homeobox-
termediate, and the vault, formed by intramembranous ossifi- containing gene and a potential modulator of downstream
cation. The membranous vault bones arise from different em- fibroblast growth factor [FGF] activity in Boston-type cranio-
bryonic origins. The frontal bones are derived from neural synostosis) and RAB23 in Carpenter syndrome. Both pheno-
crest, while the parietal bones are derived from paraxial me- typic and genetic variability occur. For example, Saethre-
soderm [1]. Calvarial bones arise in ossification centers, with Chotzen can involve one or both coronal sutures, sagittal su-
spicules of bone growing toward each other by proliferation tures or a combination of sutures. Additionally, midline sutur-
and differentiation of cells at the bone margins. Sutures form al synostosis of the sagittal and metopic sutures is common in
at the site of meeting bone fronts (Fig. 1). Interdigitating fin- Carpenter syndrome, and bicoronal synostosis in the FGFR1-
gers of bone project into the suture, with osteoblastic and 3 craniosynostosis syndromes, but all may progress to
clastic activity contributing to the fusion process. Genes gov- kleeblattschädel (cloverleaf skull deformity) [4].
ern molecules that modulate normal cranial development, With the advent of genome-wide studies, family-based stud-
such as osteoblast differentiation, vault ossification, apoptosis ies and pathological assessment of sutural stenosis, even some
or programmed cell death and sutural morphogenesis and fu- single-suture non-syndromic synostoses, which comprise ap-
sion [2]. Expression of these genes might be general or suture- proximately 80% of craniosynostosis cases, have been found
specific. For example, TWIST1 is expressed in the sutural to have genetic causes. For example, WDR35, BBS9 and BMP2
mesenchyme along frontal and parietal bone edges [3]. Pre- mutations are associated with sagittal synostosis, while FREM1
mature sutural fusion is allowed by an imbalance of gene mutations, chromosome 9p deletion, Jacobsen/11q23 deletion
expression. Genetic mutations can lead to isolated single- and various trisomies and other aneuploidies have been report-
suture or multi-suture synostosis or to a more diffuse, ed in children with metopic synostosis [4–6]. In addition, up-
syndromic type synostosis. The genes most commonly regulation or down-regulation of sutural genes and matrix

Fig. 1 Suture closure. a Frontal

and (b) lateral 3-D CT skull
reconstructions demonstrate
patent sutures in a 1-month-old
boy. c Axial 3-D CT view reveals
the skull base synchondroses. d
Synchondroses are fusing
normally and are only faintly
visible on axial 3-D CT image in a
10-month-old girl
Pediatr Radiol (2015) 45 (Suppl 3):S485–S496 487

molecules has been reported to be induced by mechanical con- radiation has led to the development and more widespread
straint, leading to intrauterine suture synostosis [7]. use of low-dose CT. Newer post-imaging reconstruction
techniques utilizing doses as low as 30 mAs on preoper-
ative studies and 20 mAs on immediate postoperative
Imaging techniques in the synostoses studies give excellent depiction of sutures [12]. As low-
dose techniques poorly define subtle intracranial findings,
Ultrasound children with complex or syndromic craniosynostoses
may benefit from MRI evaluation of the brain.
Sonography is known to be helpful in the evaluation of pos- Immediate low-dose postoperative CT can provide infor-
sible hydrocephalus or brain malformations when the fonta- mation about post-surgical extra-axial fluid collections and
nels are patent, and US has value in evaluation of suture pa- hydrocephalus. Suspicion of sinovenous thrombosis at any
tency in suspected single-suture synostosis. High-frequency stage requires CT or MR venographic evaluation. Complica-
US is capable of evaluating the width of sutures, adjacent bone tions are more common in multi-suture than single-suture syn-
thickness, partial or complete synostosis or bone overlap in ostosis repair, and reoperation has been shown to have an
positional plagiocephaly [8]. Sutures are considered abnormal increased risk of dural tears and cerebral spinal fluid (CSF)
if lacking a beveled or hypoechoic gap of at least 0.5 mm or leaks [13]. Developmental delay and visual loss caused by
more. In a study of 44 infants suspected of having craniosyn- progressive calvarial growth restriction with evidence of in-
ostosis because of small head circumference or skull deformi- creased intracranial pressure have been reported in up to 6.2%
ty, comparison between US and CT of the sutures revealed of children undergoing cranial vault reconstruction for non-
concordance of findings in 43 cases. One child with com- syndromic single-suture synostosis, more commonly in boys
pound synostosis was properly diagnosed by CT only. Au- undergoing surgery for sagittal synostosis at 5 months or
thors noted the need for specific training because US is younger. CT demonstrated intracranial crowding, scalloping
operator-dependent [9]. Another study comparing sonography of the inner table of the skull and multiple suture stenoses.
with CT found that sonography correctly identified suture Increased intracranial pressure was confirmed by intracranial
stenosis in 5 of 7 cases of CT-confirmed sagittal or lambdoid pressure monitoring [14]. In addition to signs of intracranial
synostosis, while sutural patency was confirmed by US in 45 hypertension, late follow-up CT also evaluates for the
of 47 infants with CT-confirmed posterior positional presence of progressive stenosis. Secondary coronal syn-
plagiocephaly [10]. ostosis was identified on 2-year follow-up CT in 89% of
37 children who had undergone primary surgical repair of
Radiography and CT isolated and nonsyndromic sagittal suture synostosis,
while 15% showed an additional partial lambdoid synos-
Conventional radiographs are still used at some centres as tosis. Only one child required reoperation because of the
the first imaging evaluation of abnormal calvarial config- presence of papilledema and intracranial hypertension
uration. However, findings such as sutural narrowing or [15]. Another study of 42 patients following total cranial
indistinctness, bony bridging, alterations in calvarial vault remodeling for isolated sagittal synostosis revealed a
shape and fontanel closure are better shown by low-dose significantly higher rate of lambdoid (74.5%) than coronal
CT in children who are being evaluated for cranial synostosis [16]. Children with TWIST1-confirmed
reshaping procedures, who have complicating syndromes Saethre–Chotzen syndrome are particularly likely to re-
or who have suspected multi-sutural involvement. Al- stenose following primary intervention, with up to 59%
though the value of CT and 3-D reconstruction of the developing intracranial hypertension and requiring a sec-
skull in evaluating craniosynostosis has long been appre- ond calvarial surgery [17, 18]. Children with TCF12-con-
ciated, the use of CT in clinically suspected single-suture firmed Saethre–Chotzen syndrome do not share the same
synostosis is controversial. Some authors suggest that high rate of reoperation from increased intracranial hyper-
clinical observation might be all that is required [11]. A tension, a feature that could impact the imaging follow-up
comparison of clinical versus CT evaluation of single- required [3].
suture synostosis in 131 cases of nonsyndromic cranio-
synostosis showed that although 93% had concordance Magnetic resonance imaging
between clinical and CT evaluation, incomplete diagnosis
or misdiagnosis was identified in 6 children on the basis Formerly the utility of MRI in children with cranial synos-
of clinical evaluation alone. Abnormal findings included tosis was limited to the evaluation of the underlying brain.
unsuspected additional sutural stenosis and intracranial The presence of brain abnormalities, including deformations
brain abnormalities including tumors, atrophy and anom- and malformations, is known to be associated with more
alies. Concern over the long-term effects of ionizing complex syndromic craniosynostoses. Over-convoluted
488 Pediatr Radiol (2015) 45 (Suppl 3):S485–S496

temporal lobe cortex, midline deficiencies, and developmen- include trapezoidal head shape, mastoid bulge, tilt of the cra-
tal white matter defects occur in Apert syndrome and other nial base and a relatively pulled-back ear position. Radio-
disorders associated with fibroblast growth factor receptor graphs were formerly used to differentiate the disorders
(FGFR) gene defects [19]. Brain abnormalities are also seen and unfortunately are still ordered in outpatient settings.
in the single-suture craniosynostoses. For example, metopic There is often difficulty with visualization of the entire
synostosis is associated with holoprosencephaly and with lambdoid suture, in part because of the difficulty with
brain growth failure, either acquired or congenital, as in obtaining orthogonal views in an asymmetrical skull. In-
microcephaly vera. Hydrocephalus, asymmetry of the complete visualization of the suture because of obliquity
pericerebral fluid spaces and acquired Chiari 1 malformation often leads to further imaging and considerable parental
can be seen in either multi- or single-suture stensoses. Chiari anxiety. If clinical differentiation is not possible, low-dose
1 cerebellar tonsil protrusion may be seen in 9% of children CT is a better choice (Fig. 2). A parallelogram configuration
with sagittal synostosis [20] or may be seen following ste- in positional plagiocephaly on axial CT or MRI images re-
nosis of bilateral lambdoid sutures in the presence of flects the combination of ipsilateral frontal bossing and uni-
syndromic multi-sutural synostosis, both scenarios reflecting lateral lambdoid flattening. Additional CT imaging features
a small bony posterior fossa [19]. MRI 3-D skin surface include focal sutural narrowing, sclerosis, fusion or overlap.
reconstructions are now readily performed following acqui- Additionally, endocranial ridging is present, rather than the
sition of T1 volume data sets. Evaluation of sutures is also ectocranial ridging occurring in true lambdoid synostosis.
possible with black bone MRI source sequences. Calvarial Sonographic confirmation of patent lambdoid sutures is
3-D surface reconstruction of black bone source images is used at some centers in differentiating positional
promising but requires additional software, is compromised plagiocephaly from unilateral lambdoid synostosis [25].
by patient movement and other potential artifacts, is less
sensitive in older individuals because of the intrinsic signal
Lambdoid synostosis
intensity of juxta-sutural bone, and remains more labor-
intensive than CT [21]. MRI with black bone technique is
True isolated lambdoid synostosis is one of the least common
likely to play a very important role with further development
of the synostoses, representing less than 5% of isolated non-
of technical factors. Currently, both MRI and low-dose CT
syndromal craniosynostosis cases. A trapezoid configuration
are often required to fully evaluate children with multi-
is seen in lambdoid synostosis when viewed from the vertex,
sutural or syndromic cases of craniosynostosis, which in-
reflecting ipsilateral occipital flattening with contralateral
volve orbital compromise, brain malformations, intracranial
frontal bossing. Growth at a patent mastoid fontanel, also
hypertension, venous outflow and complex anatomy of the
known as the posterolateral fontanel, leads to the typical mas-
skull base [22].
toid bump (Fig. 3). Bilateral isolated lambdoid synostosis is
extremely rare (1 in 100,000 births) and can be a marker of
Nuclear medicine
underlying rhombencephalosynapsis. Bilateral lambdoid syn-
ostosis can also be seen in the syndromic synchondroses, such
Nuclear medicine is rarely utilized in the evaluation of cranio-
as in Apert or Pfeiffer syndromes, progressing to
synostosis. A recent report documents resolution of regional
kleeblattschädel (Fig. 4) [26, 27].
cerebral hemispheric perfusion abnormalities following surgi-
cal release of craniosynostosis [23].
Sagittal synostosis

Specific imaging patterns in the craniosynostoses The most common craniosynostosis is sagittal synostosis,
comprising 40–60% of cases. Approximately 80% of sagittal
Posterior positional plagiocephaly synostosis cases are isolated and non-syndromal. Boys and
multiple births are overrepresented and genetic causes are be-
Posterior positional plagiocephaly is also known as non- coming known [28, 29]. The male predominance found in
synostotic lambdoid flattening. It is the most common etiolo- metopic and sagittal suture synostoses can be explained by
gy of abnormal skull shape in the infant. Its incidence has the role of androgens on sutural osteogenesis [30]. Skull
increased with the “Back to Sleep” campaign to reduce sud- growth occurs at patent coronal and metopic sutures, leading
den infant death syndrome (SIDS) by supine positioning of to typical frontal bossing with anterior inclination of the fore-
infants during sleep. Clinical differentiation between position- head and widened intraorbital distance. Growth at the
al plagiocephaly and unilateral lambdoid synostosis is report- lambdoid sutures leads to occipital bulging and prominence,
ed to be difficult [24]. However, typical clinical features while restriction from sagittal synostosis produces the combi-
strongly support the presence of lambdoid synostosis. These nation of elongated cranium, flat vertex and narrow cranial
Pediatr Radiol (2015) 45 (Suppl 3):S485–S496 489

Fig. 2 Posterior positional

plagiocephaly. a Submentovertex
radiograph demonstrates left
lambdoid flattening and a
parallelogram configuration in a
5-month-old girl. b Townes view
confirms patency of the
visualized lambdoid sutures
(arrows), although the sutures are
poorly visualized as they extend
to the skull base. c Axial CT in
another infant, this one a
7-month-old girl, also shows
significant left lambdoid
flattening with patent lambdoid
sutures (arrow). d Symmetrical
patent lambdoid sutures (arrow)
are shown in same infant as in (c)
on brow-down 3-D skull view

Fig. 3 Combined unilateral

coronal and lambdoid synostosis.
a Anteroposterior radiograph
demonstrates a left “harlequin
eye” (long arrow) and mastoid
bump (short arrow) in a 2-month-
old boy. b Left unilateral coronal
synostosis is seen on
anteroposterior 3-D calvarial
reconstruction. c Posterior 3-D
calvarial reconstruction reveals
unilateral lambdoid synostosis
(black arrow) and again shows
ipsilateral mastoid bump (white
arrow). d Axial 3-D cutaway view
demonstrates trapezoidal shape of
the skull with an angled skull base
490 Pediatr Radiol (2015) 45 (Suppl 3):S485–S496

Fig. 4 Kleeblattschädel in
Pfeiffer syndrome type 2. a
Coronal T1-W MR image in a
3-day-old girl with Pfeiffer type 2
demonstrates a cloverleaf skull.
Temporal horns are dilated with
vertical hippocampi, and
temporal lobes fill the
outpocketing of the skull formed
by bulging at the enlarged
squamosal sutures shown on b,
lateral 3-D calvarial
reconstruction. c, d Posterior 3-D
reconstructions obtained in the
same child at 15 days of age (c)
and at 11 weeks of age (d)
demonstrate sagittal and
progressive bilateral lambdoid
synostosis. Foci of bone thinning
have increased in number, with
progressive synostosis and
increasing intracranial pressure.
No foci of thinning are identified
at the site of the subjacent torcular
herophili (arrow), a relatively
thicker area of bone due to dural
attachments

width. Fusion may involve any part of the superior sagittal in sagittal synostosis [33]. Imaging hallmarks of early metopic
suture but is usually posterior (Fig. 5) [29, 31]. synostosis are hypotelerism, trigonocephaly, narrowed anteri-
or cranial fossa and ethmoidal hypoplasia. An additional fea-
ture is an endosteal notch (omega sign) rather than an endos-
Metopic synostosis teal spur (M-sign) at the site of normal anterior falx insertion
[34–36]. Associated upward deviation of the medial orbital
Metopic synostoses were thought to represent less than 10% rim leads to a quizzical appearance of the orbits. Skull base
of craniosynostoses overall, although recent studies suggest narrowing also occurs because metopic fusion starts at the
an increasing incidence, making it the second most common glabella (Fig. 6).
form of craniosynostosis [32]. The metopic suture is unlike
the other sutures, having its origin in mesenchyme populated
by neural crest cells [2]. Expansion of frontal bone ossification Coronal synostosis
centers is visible at 9 weeks on fetal US and leads to delinea-
tion of the metopic suture during the second trimester. The The coronal synostoses have more complicated effects
metopic suture closes from the glabella, extending upward on craniofacial appearance than do the midline synosto-
toward the anterior fontanel. Metopic closure starts in the third ses (sagittal and metopic). Children with coronal synos-
trimester and is usually complete by 9 months of postnatal life. toses are more likely to be female and to have extensive
The majority (64–75%) of cases identified in the postnatal skull base involvement. The harlequin deformity, which
period are non-syndromic and isolated. Therefore, up to one- is the most consistent orbital imaging feature of bilateral
third of children affected are syndromal or have associated or unilateral coronal synostosis, occurs because of supe-
brain abnormalities, such as microcephaly vera, rior elevation of the lesser wing of the sphenoid and is
holoprosencephaly or atrophy [28]. Boys and multiple births associated with a patent ipsilateral frontosphenoidal su-
are overrepresented in series of metopic synostosis, as they are ture (Figs. 3 and 7). Ipsilateral supraorbital and lateral
Pediatr Radiol (2015) 45 (Suppl 3):S485–S496 491

Fig. 5 Sagittal synostosis. a

Sagittal T1-weighted MR image
demonstrates scaphocephaly and
Chiari 1 malformation (arrow) in
an 18-month-old girl. b Lateral
3-D projection of the calvarium in
a 13-day-old boy with
scaphocephaly reveals patent
coronal, squamosal and lambdoid
sutures. c Oblique 3-D projection
in the same boy demonstrates
bridging of the posterior sagittal
sinus (arrow). d Axial 3-D
projection shows frontal bossing,
enlarged anterior fossa and a
narrow occiput

Fig. 6 Metopic suture synostosis.

a Axial sonogram in a 12-month-
old boy reveals a fused, beaked
metopic suture (arrow). b Axial
3-D calvarial reconstruction in a
5-month-old girl shows
trigonocephaly with patent
lambdoid, sagittal and coronal
sutures, with a patent anterior
fontanel. c Frontal 3-D view in the
same girl demonstrates fusion of
the metopic suture with
hypotelorism. d Oblique 3-D
view demonstrates beaking of the
metopic suture (arrow)
492 Pediatr Radiol (2015) 45 (Suppl 3):S485–S496

orbital rim retrusion occurs and is more severe with minor suture involvement or partial involvement of the coro-
frontosphenoidal suture involvement. Orbit deformity nal hemi-ring, however, can lead to progressive facial defor-
leads to hypertropia, superior oblique muscle dysfunc- mity by effects on adjacent sutures. Both isolated
tion (or absence), amblyopia and astigmatism [37]. frontosphenoidal and zygomaticotemporal suture stenosis
have been reported. Nasomaxillary suture involvement leads
to eventual deviation of the nasal root toward the side of the
Unilateral coronal synostosis stenosed suture (Fig. 7) [38–40].

Unilateral coronal synostosis is not uncommon, account-

ing for 20–30% of synostoses in infancy. Formerly con- Bilateral coronal synostosis
sidered to be non-syndromic and isolated, genetic muta-
tions in the TWIST1, TCF12 and pro250arg FGFR3 Shortening of the anterior cranial fossa and brachy- or
genes are now implicated in some cases with unilateral oxycephaly are seen in the bilateral coronal synostosis.
coronal synostosis. Bony shortening of the orbital roof, walls and floors
Synostosis begins in the coronal suture and extends supe- leads to shallow orbits. Resultant exorbitism and visual
riorly and inferiorly. Fusion of one coronal suture leads to compromise can be severe. Variable midface hypoplasia
restriction of anteroposterior growth ipsilateral to the stenosed caused by skull base involvement is common in
suture. There is variable extension from the middle of the syndromal cases of bilateral, coronal synostosis. In-
coronal suture to involve the sphenoethmoidal synchondrosis volvement of the posterior fossa sutures and skull base
and frontosphenoidal suture of the basilar coronal hemi-ring, synchondroses is also common in severe Pfeiffer
with resultant shortening of the ipsilateral sphenoid, and tem- (Fig. 4), Apert (Fig. 8) and Crouzon (Fig. 9) syn-
poral and zygomatic bones. Continued growth at the contra- dromes, with resultant distortion of the petrous ridge
lateral suture leads to eventual angling of the sagittal suture and bony skull base, small bony posterior fossa and
and cranial base toward the stenosed coronal suture. Even foramen m agnum coarctation [34]. Progressive

Fig. 7 Unilateral coronal

synostosis. a Coronal US in a 13-
day-old boy with Muenke
syndrome and unilateral coronal
synostosis reveals upward
displacement of the left orbital
roof (arrow). b Coronal CT and
(c) frontal 3-D skull
reconstruction demonstrate a
harlequin appearance with
elevated left orbital roof (arrow,
b) in a 4-month-old with
unilateral coronal synostosis. c
Also shown are unilateral coronal
synostosis with bridging (arrow),
ipsilateral frontal bone
plagiocephaly, angled sagittal
suture and nasal tilt. d Axial T2-
weighted MRI in same infant seen
in (a), now 3 years of age, shows
deformation of the left frontal
lobe in association with calvarial
plagiocephaly
Pediatr Radiol (2015) 45 (Suppl 3):S485–S496 493

Fig. 8 Apert syndrome. a

Beveled edges of the widened
sagittal suture (arrows) are
identified on coronal sonogram in
a 17-day-old girl with Apert
syndrome. b Frontal 3-D skull
reconstruction in the same child at
4 months of age confirms bilateral
coronal synostosis. c Axial 3-D
view demonstrates shallow orbits
in the same infant, who clinically
has exorbitism. d Three-
dimensional CT hand
reconstruction with CT
angiography performed
preoperatively shows distal
phalangeal fusion (arrow) in a 5-
year-old with typical Apert type 2
syndactyly

pansynostosis with cloverleaf skull deformity or occurs in Saethre–Chotzen. Children with Boston-type
kleeblattschädel can occur in the syndromic bicoronal craniosynostosis have varying degrees of cutaneous syn-
synostoses (Fig. 4). dactyly of the fingers. Children with Muenke syndrome
There is variable expressivity and severity and considerable demonstrate brachyphalangia, metatarsal or metacarpal
phenotypic overlap in the syndromic bicoronal synostoses. fusion, while children with Pfeiffer syndrome have
FGFR1-3 gain-of-function mutations are seen in Apert broad first digits of the hands and feet. Radial aplasia
(OMIM# 101200), Crouzon (OMIM# 602849), Crouzon with or hypoplasia is reported in Baller–Gerold syndrome
acanthosis nigricans (OMIM# 612247), Muenke (OMIM# (OMIM# 218600/RECQL4), while Jackson–Weiss syn-
602849), Pfeiffer (OMIM# 101600), Jackson–Weiss (OMIM# drome (described in an Amish kindred) is associated
123150) and Beare–Stevenson cutis gyrata (OMIM# 123790) with tarsal–metatarsal fusion, and broad first metatarsals
syndromes. Boston-type craniosynostosis (OMIM# 604757) and proximal phalanges of the feet [41].
is caused by an MSX2 mutation, while Saethre–Chotzen
(OMIM# 101400) usually exhibits TWIST1 loss-of-function Other patterns
mutations.
Because kleeblattschädel and isolated unicoronal cra- While pansynostosis may be seen with many of the syndromic
niosynostosis can present with the same mutation, diag- complex craniosynostoses, it can also follow severe early
nosis requires both radiographic and genetic evaluation. brain injury, most commonly perinatal hypoxic–ischemic in-
For example, the presence of extremity malformations, sult (Fig. 10). Other unusual combinations of rather non-
which are common in the syndromic craniosynostoses, specific sutural synostoses occur, including Z-shaped cranio-
aids in clinical and radiologic classification. The degree synostosis (fusion of unilateral coronal, contralateral
of bony and soft-tissue syndactyly of hands and feet lambdoid and intervening sagittal sutures) and Mercedes
and elbow ankylosis in Apert syndrome correlates with Benz craniosynostosis (fusion of sagittal and bi-
specific FGFR2 mutations (Fig. 8). Variable presence of lambdoid sutures) [42, 43]. Multisutural synostosis
syndactyly of hand digits 2–3 and radioulnar syndactyly should prompt genetic evaluation.
494 Pediatr Radiol (2015) 45 (Suppl 3):S485–S496

Fig. 9 Crouzon syndrome. a

Sagittal T1-weighted image in a
12-year-old boy with prior vault
reconstruction for Crouzon
syndrome shows a small posterior
fossa with Chiari 1 malformation
(short arrow) and multiple
serpiginous vascular structures in
the posterior scalp (long arrow). b
MR venogram reveals these as
extensive venous collaterals in
association with occlusion of the
posterior superior sagittal sinus,
the straight sinus and the torcular
heropholi. c Axial CT in the same
child shows medialization of the
bony carotid canal (arrow). d MR
angiogram confirms marked
carotid medialization (arrow) or
“kissing carotids”

Fig. 10 Acquired pansynostosis.

a Coronal diffusion-weighted
image obtained in a 3-day-old boy
with a history of hypoxic–
ischemic insult at birth
demonstrates extensive bright
signal (diffusion restriction) of the
entire supratentorial brain
(arrow). By comparison,
infratentorial structures are
normal in signal. b Follow-up
axial CT shows ridging and fusion
of the coronal sutures. c Three-
dimensional skin surface
reconstruction and (d) frontal 3-D
skull reconstruction show ridging
at the site of fused, overlapped
sutures (arrow) and microcephaly
Pediatr Radiol (2015) 45 (Suppl 3):S485–S496 495

Conclusion 15. Kuang AA, Jenq T, Didier R et al (2013) Benign radiographic coronal
synostosis after sagittal synostosis repair. J Craniofac Surg 24:937–
940
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Conflicts of interest Drs. Blaser, Padfield, Chitayat and Forrest have
Nerv Syst 23:1379–1388
no financial interests, investigational or off-label uses to disclose.
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