Pediatr Radiol

DOI 10.1007/s00247-015-3300-5

ORIGINAL ARTICLE

Neuroimaging features of Cornelia de Lange syndrome

Matthew T. Whitehead & Usha D. Nagaraj &
Phillip L. Pearl

Received: 25 July 2014 / Revised: 18 November 2014 / Accepted: 4 February 2015

# Springer-Verlag Berlin Heidelberg 2015

Abstract anomalies included scoliosis, segmentation anomalies,

Background Cornelia de Lange syndrome is a rare genetic
disease characterized by distinctive facial dysmorphia and
dwarfism. Multiple organ system involvement is typical. Var-
ious central nervous system (CNS) aberrations have been de-
scribed in the pathology literature; however, the spectrum of
neuroimaging manifestations is less well documented.
Objective To present neuroimaging findings from a series of
eight patients with Cornelia de Lange syndrome.
Materials and methods The CT/MR database at a single aca-
demic children’s hospital was searched for the terms “Corne-
lia,” “Brachmann” and “de Lange.” The search yielded 18
exams from 16 patients. Two non-CNS and six exams without
available images were excluded. Ten exams from eight pa-
tients were evaluated by a board-certified neuroradiologist.
Results All patients had skull base dysplasia, most with an
unusual coronal basioccipital cleft (7/8). All brain MR exams
showed microcephaly, volume loss and gyral simplification
(5/5). Six patients had an absent massa intermedia. Four pa-
tients had small globe anterior segments; three had optic path-
way hypoplasia. Basilar artery fenestration was present in two
patients; vertebrobasilar hypoplasia was present in one pa-
tient. The inner ear vestibules were dysplastic in two patients.
One patient had pachymeningeal thickening. Spinal
M. T. Whitehead (*) : U. D. Nagaraj : P. L. Pearl
Department of Radiology,
111 Michigan Ave. NW, Washington, DC 20010, USA
e-mail: matthewthomaswhitehead@gmail.com
U. D. Nagaraj
Department of Radiology,
Cincinnati Children’s Hospital,
Cincinnati, OH, USA
P. L. Pearl
Department of Neurology,
Boston Children’s Hospital,
Boston, MA, USA
endplate irregularities, basilar invagination, foramen magnum
stenosis and tethered spinal cord.
Conclusion Typical imaging manifestations of Cornelia de
Lange syndrome include skull base dysplasia with coronal
clival cleft, cerebral and brainstem volume loss, and gyral
simplification. Membranous labyrinth dysplasia, anterior seg-
ment and optic pathway hypoplasia, basilar artery fenestra-
tion, absent massa intermedia and spinal anomalies may also
be present.
Keywords Cornelia de Lange syndrome . Brachmann de
Lange syndrome . Clivus . Skull base . Fenestration . Anterior
segment . Hypoplasia . Micrencephaly . Segmentation .
Children . Magnetic resonance imaging
Introduction
Cornelia de Lange syndrome (also called Brachmann de
Lange syndrome) is an autosomal- dominant, generally spo-
radic disease that manifests with typical facial dysmorphism,
growth impairment and multisystemic manifestations particu-
larly including intellectual deficiency, limb anomalies, con-
genital heart defects and gastrointestinal disease. The syn-
drome has been classified as a cohesinopathy because genes
encoding cohesin complex proteins are consistently involved
[1]. The cohesin complex governs chromosomal division, sep-
aration, architecture and transcription [2]. The protein elabo-
rated from the NIPBL (Nipped-B homolog) gene is responsi-
ble for cohesin complex – chromatin attachment and promoter
activation [2]. Therefore, NIPBL defects disrupt normal mito-
sis and meiosis in cells throughout the body. Mutations of five
different genes have been identified thus far: SMC1A, SMC3,

NIPBL, RAD21 and HDAC8 [1]. Defects in SMC1A, SMC3
and NIPBL are responsible for the clinical phenotype in 60–
65%; the latter is associated with increased severity [1, 3, 4].
Distinctive facial features in classical phenotypes (arched eye-
brows, long philtrum, thin lips, anteverted nose, crescent-
shaped mouth and synophysis) are diagnostic [5–8]. However,
patients exhibiting mild signs and symptoms of Cornelia de
Lange syndrome may be underdiagnosed. A confirmatory test
could be a useful diagnostic adjunct in this circumstance.
Epilepsy has been reported in a large percentage of patients
(up to 80%, average 20%), often with focal epileptiform ac-
tivity on electroencephalogram [4, 9, 10]. Seizures are the
most common central nervous system clinical manifestation
[4, 5, 9]. Nevertheless, radiologic and histopathological re-
ports presenting CNS aberrations in Cornelia de Lange syn-
drome are sparse. Some of the previously described congenital
brain and temporal bone abnormalities include parenchymal
hypoplasia (especially involving midline structures),
malformations of cortical development such as abnormal cor-
tical convolutions and gray matter heterotopia, inner ear dys-
plasia and middle/external ear hypoplasia [5, 11, 12]. Clastic
(destructive) brain lesions may also be present, presumably a
consequence of concurrent congenital heart disease in some of
these patients [12]. In terms of the craniofacial and axial skel-
etal system, cervical segmentation anomalies, mandibular hy-
poplasia and cleft palate have been described [13–15]. The
purpose of this study is to show additional newly discovered
characteristic brain and skeletal anomalies from a series of
eight patients with Cornelia de Lange syndrome.
Materials and methods
This HIPAA compliant retrospective study was performed
after Institutional Review Board approval. Requirement for
informed consent was waived. The imaging database at a sin-
gle academic children’s hospital was queried for the terms
“Cornelia de Lange,” “de Lange” and “Brachmann de Lange”
after filtering by modality (CT and MR). Eighteen exams were
identified from 16 patients performed during a 14-year period
(1999–2013). Two non-CNS exams were excluded (chest and
lower extremity MRIs). The remaining six exams excluded as
images were not available for direct review. All exams were of
diagnostic quality. Magnetic resonance studies were per-
formed on either 1.5- or 3.0-Tesla scanners (General Electric,
Milwaukee, WI). Sagittal T1-WI, axial T2-WI, axial T2 fluid
attenuated inversion recovery (FLAIR), coronal fat-saturated
T2-WI and axial diffusion tensor imaging (DTI) images with
15 non-collinear directions of encoding were reviewed. Axial
T1-WI and coronal fat saturated T1-WI of the brain were
performed after IV gadolinium administration in one patient.
CT images of the head, temporal bone, and/or cervical spine
were acquired on a 16-detector scanner (General Electric,
Pediatr Radiol
Milwaukee, WI). Electronic medical records of all patients
were reviewed for symptomatology, past medical history and
confounding variables that could cause secondary CNS pa-
thology such as congenital heart disease.
Studies were reviewed in a blinded manner by a
fellowship-trained neuroradiologist (M.T.W.) with American
Board of Radiology subspecialty certificate in neuroradiology
and 3 years of clinical experience after board certification.
Imaging studies were qualitatively examined for all visible
abnormalities involving the brain and its coverings, head and
neck, and spine. Because follow-up studies were not available,
we used the term brain parenchymal volume loss to encom-
pass both hypoplasia (underdevelopment) and atrophy
(wasting). Cerebellar hypoplasia was diagnosed according to
definitions of cerebellar atrophy and hypoplasia, as defined by
Barkovich [16]. Skull base hypoplasia was diagnosed subjec-
tively based on the appearance of the occipital bone relative to
the sizes of posterior fossa CSF spaces and parenchyma.
All patients in this series were either diagnosed clinically
(n=5) or clinically and molecularly (n=3) with Cornelia de
Lange syndrome.
Results
A total of 10 exams from 8 patients, ages 7 months to 21 years
(mean: 9 years) with an equal gender distribution, met inclu-
sion criteria. Clinical manifestations are shown in Table 1.
Imaging features are displayed in Table 2.
Brain, vasculature and meninges
In all patients with available brain MR imaging (5/5),
micrencephaly, parenchymal volume loss and gyral simplifi-
cation were present. Parenchymal volume loss was variable in
degree and extent, but generally diffuse involving both gray
and white matter structures of the cerebrum, cerebellum and
brainstem (Fig. 1). The normal interthalamic adhesion (massa
intermedia) was absent in six patients (Fig. 1); the massa
intermedia were not diagnostically evaluable in the remaining
two patients.
The vertebrobasilar system flow-voids were abnormal in
three patients, although dedicated vascular imaging was not
performed. Basilar artery fenestration was present in two pa-
tients and vertebrobasilar hypoplasia was present in one pa-
tient (Fig. 2). One patient exhibited diffuse dural thickening
and contrast enhancement (Fig. 3).
Skull base
All patients had skull base hypoplasia and/or dysplasia. A
unique coronal cleft involving the basiocciput was present in
most patients (n=7) (Figs. 1 and 4).
Pediatr Radiol

Table 1 Clinical manifestations

Pt 1 Pt 2 Pt 3 Pt 4 Pt 5 Pt 6 Pt 7 Pt 8

Gene defect NIPBL NT NT NIPBL NT NIPBL NT ?

Facies + + + + + + + +
Limb anomalies + normal + + + + normal ?
Cardiac TOF TOF normal normal ASD,VSD normal normal ?
GI GERD GERD GERD normal GERD GERD normal ?
Hearing SNHL CHL MHL SNHL SNHL SNHL CHL ?
Neurological DD, Sz DD DD, Sz DD,Sz encephalopathy DD DD ?
GU MP normal normal normal normal HS, MP ? ?
Ophthalmic normal normal My, As, ONP normal normal normal normal ?

Clinical features of eight patients (Pt) with Cornelia de Lange syndrome

As astigmatism, ASD atrial septal defect, CHL conductive hearing loss, DD developmental disability, GI gastrointestinal, GU genitourinary, HS
hypospadias, MHL mixed hearing loss, MP micropenis, My myopia, NT not tested, ONP optic nerve pitting, SNHL sensorineural hearing loss, Sz
seizure, TOF tetralogy of Fallot, VSD ventricular septal defect, ? unknown
Facies facial dysmorphia specific for Cornelia de Lange syndrome such as arched brows, long philtrum, anteverted nose, crescent-shaped mouth and thin
lips with or without hypertrichosis
+ abnormal/involved

Temporal bone (incomplete partitioning type II or IP-II) was present

Bilateral vestibular dysplasia was present in two of
three patients with dedicated thin section temporal bone
images (CT: n = 2; MR: n = 1). Both of these patients
demonstrated focal posteromedial vestibular protrusions
(Fig. 5). Bilateral malleus and incus malformations
compatible with ossicular dysplasia were present in
two patients. Bilateral cochlear hypoplasia/dysplasia
in one patient. One patient had bilateral cholesteatomas
and ossicular erosions.
Ocular
Small anterior globe segments were seen in four of six patients
where the globes were visible (Fig. 6). Three patients had

Table 2 Imaging features

Pt 1a 1b 2 3a 3b 4 5 6 7 8

Age 8m 1y 21y 2y 7y 11y 1y 7m 21y 7m

Exam Head CT Brain MR C-spine/ Head CT T-bone CT Head CT/ Brain MR Brain MR Spine MR Brain MR
T-bone CT T-bone CT
Cerebrum VL VL,MCD NI VL NI WNL VL, MCD VL, MCD VL, MCD VL, MCD
MI ? A NI A NI A A A ? A
Cerebellum VL VL NI VL NI VL VL VL VL WNL
Brainstem VL VL NI VL NI WNL VL VL VL WNL
T-bone ? ? C,OE ? OD VD, IP2, OD VD ? NI ?
Ocular ASH ONH, ASH NI ASH ASH ASH ONH, ASH ONH NI WNL
Meninges ? ? ? ? ? ? DE ? ? ?
Vessels ? WNL ? ? ? ? BAF BAF VBH WNL
Spine NI SA SA SA ? ? ? ? AAS, SA, TSC, ?
EI, FMS, scoli
Skull base PCC PCC PCC, H PCC PCC H CCC PCC PCC, BI CCC

Neuroimaging findings from eight patients (Pt) with Cornelia de Lange syndrome
A absent, AAS atlantoaxial subluxation, ASH anterior segment hypoplasia, BAF basilar artery fenestration, BI basilar invagination, C cholesteatoma, CCC
complete coronal cleft, DE dural enhancement, EI endplate irregularities, FMS foramen magnum stenosis, H hypoplasia, IP2 incomplete partitioning
type II, MCD malformation of cortical development, MI massa intermedia, NI not imaged, OD ossicular dysplasia, OE ossicular erosions, ONH optic
nerve hypoplasia, PCC partial clival cleft, SA segmentation anomalies, scoli scoliosis, T-bone temporal bone, TSC tethered spinal cord, VBH
vertebrobasilar hypoplasia, VD vestibular dysplasia, VL volume loss, WNL within normal limits, ? unknown

Fig. 1 Midline sagittal spoiled gradient recalled acquisition in the steady
state (SPGR) T1-W (3-T MR; repetition time 12 ms, echo time 7 ms,
inversion time 450 ms; slice thickness, 1 mm; slice spacing, 0.5 mm;
matrix, 256 × 256) of a 1-year-old boy with Cornelia de Lange
syndrome shows a small brain-to-face ratio compatible with
micrencephaly, a simplified gyral pattern, cerebellar hypoplasia and
brainstem volume loss, predominantly involving the pons. The massa
intermedia is absent (small arrow). A distinctive coronally oriented cleft
is present in the clivus (large arrow)
optic pathway hypoplasia (Fig. 6). However, dedicated orbital
imaging was not acquired.
Spine
Spinal anomalies included segmentation anomalies (n=
4), basilar invagination (n=1), atlantoaxial subluxation
and foramen magnum stenosis (n=1), endplate irregular-
ities (n=1), scoliosis (n=1) and tethered spinal cord (n=
1) (Figs. 7 and 8).
Fig. 2 Coronal fat-saturated T2-W (3-T MR; repetition time 6,551 ms,
echo time 75 ms; slice thickness, 3 mm; slice spacing, 3 mm; matrix,
288 × 288) of a 1-year-old boy with Cornelia de Lange syndrome
demonstrates basilar artery fenestration (arrow). Note generalized
cerebral volume loss with diffuse sulcal enlargement and commensurate
ventriculomegaly
Pediatr Radiol
Fig. 3 Coronal fat-saturated T1-W (3-T MR; repetition time 667 ms, 11
echo time ms; slice thickness, 1.2 mm; slice spacing, 0.6 mm; matrix,
288×288) acquired after intravenous gadolinium administration (1.1 mL
gadopentetate dimeglumine) in a 1-year-old boy with Cornelia de Lange
syndrome demonstrates generalized dural thickening and
hyperenhancement (arrows)
Discussion
Cornelia de Lange syndrome is a systemic disorder, affecting
multiple organs (Table 1). Specific organ system abnormali-
ties include cardiac (structural anomaly in 33%), auditory
(80% hearing loss), genitourinary (41%), gastrointestinal (gas-
troesophageal reflux in 65%), skeletal (including delayed mat-
uration, microcephaly, limb/digital anomalies, abnormal tho-
racic configuration, flat acetabular angles), brain (intellectual
disability, developmental delay and seizure) and ophthalmo-
logical (ptosis, nystagmus, high myopia, poor macula reflex,
hypertropia, nasolacrimal duct fistula, corneal opacities)
[17–23]. Prenatal diagnosis is suspected in patients exhibiting
the constellation of growth retardation, limb defects, hirsutism
and diaphragmatic hernia [24]. Typical facial features (Fig. 9)
in a patient with upper limb defects, growth deficiency and
intellectual disability are essentially diagnostic of Cornelia de
Lange syndrome. Conversely, mild phenotypes may be
underdiagnosed. All patients in this series were either diag-
nosed clinically (n=5) or clinically and molecularly (n=3).
NIPBL gene mutations were detected in the three patients
who underwent adjunctive molecular testing.
Little literature exists regarding CNS manifestations of
Cornelia de Lange syndrome. Histopathological structural
CNS abnormalities that have been described include
microbrachycephaly, abnormal gyration, migrational abnor-
malities, thickened meninges and hypoplasia of myelin, fron-
tal lobes, neurohypophysis, lateral geniculate nuclei, corpus
callosum, cerebral peduncles, ventral pons and cerebellum
[11, 12, 25, 26]. We found microcephaly, parenchymal vol-
ume loss and gyral simplification to be constant features,
though variable in degree. Frontal lobe predominant volume
loss was present in two patients. Brain malformation may be
responsible for developmental disability and epilepsy in
Pediatr Radiol

Fig. 4 Image collage depicts

Clival clefts (arrows) are depicted
in six different patients with
Cornelia de Lange syndrome.
a=axial T2-W, 7-month-old boy;
b=sagittal T1-W, 1-year-old boy;
c=sagittal T2-W, 21-year-old
man; d=sagittal T2-W, 1-year-old
boy; e=sagittal CT image,
21-year-old woman, f=sagittal
CT image, 2-year-old girl

Fig. 5 Axial CT image of the left temporal bone of an 11-year-old girl
with Cornelia de Lange syndrome depicts vestibular dysplasia with a
posteromedial protrusion (arrow)
Fig. 6 Axial T2-W (1.5-T MR; repetition time 2,683 ms, 103 echo time
ms; slice thickness, 4 mm; slice spacing, 5 mm; matrix, 256×256) of the
orbits of a 1-year-old boy with Cornelia de Lange syndrome shows small
anterior segments (small arrows) and small optic nerves, partially visible
(large arrows). The imaged cerebrum is small in volume

Fig. 7 Sagittal T2-W (1.5-T MR; repetition time 2,400 ms, 99 echo time
ms; slice thickness, 3 mm; slice spacing, 3.3 mm) of the upper cervical
spine of a 21-year-old man with Cornelia de Lange syndrome
demonstrates atlantoaxial subluxation. The posterior neural arch of the
atlas impinges upon the dorsal cervical spinal cord (black arrow);
hyperintense fluid fills the enlarged predental joint space (arrowhead).
A coronal cleft is visible in the clivus (white arrow)
Cornelia de Lange syndrome. All seven patients with avail-
able medical records had functional brain abnormalities in-
cluding developmental disability (n=6), seizures (n=3) and
encephalopathy (n=1).
The massa intermedia was absent in all patients in whom
the thalami were visible. The thalamic massa intermedia is
parenchymal tissue connecting the medial thalamic margins
comprised of neurons and axons [27]. Some believe the massa
Fig. 8 Sagittal T2-W (1.5-T MR; repetition time ms/echo time ms,
5,000/154; slice thickness, 3 mm; slice spacing, 3.3 mm) of the lumbar
spine in an 8-year-old boy depicts an abnormal caudal termination of an
elongated conus medullaris consistent with a tethered spinal cord (thick
arrow). Lumbosacral anatomy is congenitally transitional with partial
lumbarization of S1. There is advanced for age degenerative disk
disease at L4-L5 with associated disk hypointensity, disk height loss
and anterior cortical endplate irregularities
Pediatr Radiol
Fig. 9 Clinical photograph of an 8-year-old boy with Cornelia de Lange
syndrome depicts all major diagnostic criteria including arched eyebrows,
long philtrum, thin lips, anteverted nose and crescent-shaped mouth.
Hypertrichosis is also noted with bushy eyebrows and eyelashes.
Written consent to allow medical image publication was obtained from
the parents of the patient featured in this clinical photograph
intermedia to be a functionally void vestigial remnant in
humans, as it may be absent in up to 20–30% of normal indi-
viduals [27, 28]. Massa intermedia absence may be congenital
or age-dependent; older subjects are more likely than younger
patients to have absent or small massa intermedia volumes
[29–31]. It may also be absent in certain disease states such
as pituitary duplication syndrome [32] and schizophrenia [33].
Diffuse pachymeningeal thickening and enhancement was
present in the single patient who received contrast material
(Fig. 3). Cornelia de Lange associated meningeal abnormali-
ties have been described in the pathology literature [12]. Al-
though the etiology is unclear, meningeal maldevelopment is
possible.
Septo-optic dysplasia has been described in Cornelia de
Lange syndrome [26]. The septum pellucidum and
hypothalamic-pituitary axis were normal in all of our patients.
However, optic pathway hypoplasia (n=3) and shallow globe
anterior segments (n=4) were common. Be that as it may, only
one patient had clinical evidence of ocular disease consisting
of myopia, astigmatism and optic nerve pitting; this patient
also had anterior segment hypoplasia. Although a potential
pathogenic relationship cannot be fully substantiated,
suprasellar germinomas have been described in patients with
Cornelia de Lange syndrome in two separate case reports [34,
35]; however, there were no suprasellar masses present in our
patient cohort.
The vertebrobasilar system was abnormal in three of our
patients; basilar fenestration (n=2) and vertebrobasilar hypo-
plasia (n=1) were discovered. Although these findings may be
seen as incidental anomalies in normal patients, they may be
part of certain Cornelia de Lange syndrome disease
Pediatr Radiol
phenotypes. Multilevel segmental arteries contribute to forma-
tion of the vertebrobasilar system after development of the
carotids [36]. The vertebrobasilar circulation has multiple con-
nections with other longitudinal arteries including branches of
the carotids, deep cervical and ascending cervical arteries.
Mesodermally derived mesenchyme that forms the walls of
the vertebrobasilar system may be insufficiently developed or
maldeveloped as a result of cohesin complex defects in Cor-
nelia de Lange syndrome. Clastic (destructive) lesions may be
present in Cornelia de Lange syndrome; these are presumably
secondary to concurrent congenital heart disease [12]. Al-
though three patients had congenital heart disease, no focal
white matter lesions were present (Table 2).
The temporal bones should be closely evaluated in patients
with Cornelia de Lange syndrome. Histopathological tempo-
ral bone anomalies may include cochlear hypoplasia, dysplas-
tic vestibule, anomalous/dehiscent facial nerve canal, and ab-
normal mesenchymal filling of the middle ear and labyrinth
[37, 38]. Temporal bone CT abnormalities from a series of 10
Cornelia de Lange syndrome patients included external audi-
tory canal stenosis, tympanomastoid cavity hypoplasia, facial
nerve canal dehiscence, dysmorphic ossicles, hypoplastic co-
chlea and dysplastic vestibule [39]. A peculiar posteromedial
vestibular protrusion was present in most of these patients
[39]. We found cochlear hypoplasia/dysplasia in one and dys-
plastic vestibules in two patients of three examined with tem-
poral bone CT exams. Ossicular dysmorphology was present
in two patients. In both cases, the malleus and incus were
malformed, being abnormal in contour. Clefts were present
in the body of the incus bilaterally in one patient. All seven
patients with medical records available for review had hearing
loss (sensorineural, n=4; conductive, n=2; mixed, n=1).
The skeletal system is often affected in Cornelia de Lange
syndrome. Bettini et al. [13] suggested that upper cervical
imaging be acquired in all patients based on findings from a
series of three Cornelia de Lange syndrome patients with cer-
vical spine malformations, two with segmentation anomalies
and one with atlantoaxial rotary subluxation [13]. NIPBL has
been demonstrated to be involved in homeobox gene regula-
tion, responsible for axial skeleton patterning [13]. We found
spinal anomalies in most patients. Commonly, these were seg-
mentation anomalies. Other anomalies included basilar invag-
ination, atlantoaxial subluxation, scoliosis, endplate irregular-
ities and tethered spinal cord.
The skull base was universally dysgenetic in our cohort.
Unique to Cornelia de Lange syndrome was a coronal cleft of
the clivus (n=7) (Fig. 4). The cleft either partially or entirely
partitions the clivus. It is located caudal to (and clearly distinct
from) the normal spheno-occipital synchondrosis. Consider-
ing the developmental embryology of the basiocciput, the lo-
cation of the cleft is unexpected. The clivus arises from fusion
and endochondral ossification of bilateral parachordal plates
[40]. Its maturation is further complicated by an intimate
association with the cranial component of the notochord. Al-
though a fossa navicularis can occasionally be present in the
clivus as a normal variant, a coronal clival cleft has never been
described to the best of our knowledge.
In summary, brain, ocular, temporal bone, arterial and
craniospinal abnormalities common to Cornelia de Lange syn-
drome result from one or more chromosomal defects that im-
pair cohesion complex loading onto sister chromatids during
cell duplication. Mesodermally derived elements appear to be
particularly affected, including the globes, temporal bones,
occiput, vertebrobasilar system, meninges and spinal
vertebrae.
This study is limited by its retrospective nature, relatively
small sample size and wide patient age range. Also, dedicated
orbital and vascular imaging was not performed in any patient.
In spite of these limitations, the distinctive imaging findings
involving the cerebrum and brainstem, occiput, temporal
bones and spine in this series merit emphasis.
Conclusion
CNS imaging manifestations of Cornelia de Lange syndrome
include skull base dysplasia and basiocciput coronal cleft,
parenchymal hypoplasia, gyral simplification and absent mas-
sa intermedia. Membranous labyrinth dysplasia, anterior seg-
ment and optic pathway hypoplasia, vertebrobasilar abnor-
malities and spinal anomalies may also be present. We believe
that neuroimaging of the brain, head and neck, intracranial
arteries and spine may play an important role in the diagnostic
work-up of patients with Cornelia de Lange syndrome.
Acknowledgments This work was presented at the 57nd annual meet-
ing of the SPR. Washington, D.C., May 2014.
Conflicts of interest None
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