Prenatal ultrasound and magnetic resonance
imaging features in a fetus with Walker–Warburg
syndrome
A 27-year-old woman was referred for targeted ultrasound
examination at 26 weeks’ gestation following sonographic
detection of fetal ventriculomegaly and posterior
fossa abnormality. She and the father were Macedonian,
non-consanguineous, healthy and had two healthy daughters.
A mid-trimester abnormality scan had not been
performed.
On ultrasound examination the fetal cerebral ventricles
were found to be enlarged (atrial width, 14 mm), the
cerebellar vermis was not depicted and the fourth ventricle
communicated with the cisterna magna, which was not
enlarged (Figure 1). A median anechoic structure was
interposed between the lateral ventricles, suggestive of
a vein of Galen aneurysmal malformation. However,
this diagnosis was easily excluded because the structure
showed no signal on color Doppler imaging. Two days
later, magnetic resonance imaging (MRI) confirmed the
sonographic findings. Moreover, it showed a kinked
Z-shaped brainstem, with bifid pons and medulla
oblongata (Figure 2), and the mantle was thin with a
simplified gyral pattern. The association of lissencephaly
with cerebellar and brainstem anomalies suggested the
diagnosis of Walker–Warburg syndrome (WWS). WWS
is a rare autosomal recessive disorder characterized by
congenital muscle dystrophy (CMD) and complex brain
and eye abnormalities1,2. Additional ultrasound and MRI
examinations showed progressive enlargement of the
cerebral ventricles, the median anechoic structure and
the cisterna magna (Figure 1c). At 31 weeks, retinal nonattachment/
detachment and asymmetry of the eye globes
were observed (Figure 3).
At 41 weeks a male fetus was vaginally delivered, with
a birth weight of 3400 g and head circumference of
37.5 cm. The neonate showed spontaneous respiratory
activity, but was deeply hypotonic and required gavage
nutrition for impaired swallowing. Postnatal MRI showed
active hydrocephalus (necessitating ventriculoperitoneal
shunt placement), the typical ‘cobblestone’ appearance of
lissencephaly and abnormal cerebellar gyration (Figure 4).
Muscular biopsy on day 15 showed severely increased
variability of the diameter of muscle fibers and endomisial
fibrosis together with immunohistochemical reduction
of glycosylated alpha-dystroglycan2. Molecular analysis
showed a homozygous mutation in the protein-Omannosyltransferase
1 (POMT1) gene (c.1611C>G,
p.Ser537Arg), which has previously been detected in other
cases of WWS3,4. The infant died at 6 months of age.
In fetuses postnatally proven to be affected by WWS,
the cerebral anomalies detected by prenatal sonography
are usually non-specific5 and suggestive of WWS only
in cases with a positive family history. When familial
history is uninformative, only the association of cerebral
or cerebellar with ocular anomalies can suggest the correct
diagnosis6,7.
In the current case, sonography showed ventriculomegaly
and dysplastic cerebellum, and the diag...
