Prenatal ultrasound and magnetic resonance imaging features in a fetus with Walker–Warburg syndrome

Prenatal ultrasound and magnetic resonanceimaging features in a fetus with Walker–WarburgsyndromeA 27-year-old woman was referred for targeted ultrasoundexamination at 26 weeks’ gestation following sonographicdetection of fetal ventriculomegaly and posteriorfossa abnormality. She and the father were Macedonian,non-consanguineous, healthy and had two healthy daughters.A mid-trimester abnormality scan had not beenperformed.On ultrasound examination the fetal cerebral ventricleswere found to be enlarged (atrial width, 14 mm), thecerebellar vermis was not depicted and the fourth ventriclecommunicated with the cisterna magna, which was notenlarged (Figure 1). A median anechoic structure wasinterposed between the lateral ventricles, suggestive ofa vein of Galen aneurysmal malformation. However,this diagnosis was easily excluded because the structureshowed no signal on color Doppler imaging. Two dayslater, magnetic resonance imaging (MRI) confirmed thesonographic findings. Moreover, it showed a kinkedZ-shaped brainstem, with bifid pons and medullaoblongata (Figure 2), and the mantle was thin with asimplified gyral pattern. The association of lissencephalywith cerebellar and brainstem anomalies suggested thediagnosis of Walker–Warburg syndrome (WWS). WWSis a rare autosomal recessive disorder characterized bycongenital muscle dystrophy (CMD) and complex brainand eye abnormalities1,2. Additional ultrasound and MRIexaminations showed progressive enlargement of thecerebral ventricles, the median anechoic structure andthe cisterna magna (Figure 1c). At 31 weeks, retinal nonattachment/detachment and asymmetry of the eye globeswere observed (Figure 3).At 41 weeks a male fetus was vaginally delivered, witha birth weight of 3400 g and head circumference of37.5 cm. The neonate showed spontaneous respiratoryactivity, but was deeply hypotonic and required gavagenutrition for impaired swallowing. Postnatal MRI showedactive hydrocephalus (necessitating ventriculoperitonealshunt placement), the typical ‘cobblestone’ appearance oflissencephaly and abnormal cerebellar gyration (Figure 4).Muscular biopsy on day 15 showed severely increasedvariability of the diameter of muscle fibers and endomisialfibrosis together with immunohistochemical reductionof glycosylated alpha-dystroglycan2. Molecular analysisshowed a homozygous mutation in the protein-Omannosyltransferase1 (POMT1) gene (c.1611C>G,p.Ser537Arg), which has previously been detected in othercases 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 sonographyare usually non-specific5 and suggestive of WWS onlyin cases with a positive family history. When familialhistory is uninformative, only the association of cerebralor cerebellar with ocular anomalies can suggest the correctdiagnosis6,7.In the current case, sonography showed ventriculomegalyand dysplastic cerebellum, and the diagnosis ofWWS was suspected after the detection of lissencephaly,bifid pons and medulla oblongata and kinked brainstemby MRI8,9. The ocular abnormalities, which confirmedthe diagnosis6,7,9, were only observed 1 month later.Late-onset microphthalmia and late diagnosis of retinaldetachment have been described previously5,10.Aside from the findings that were used to diagnoseWWS, listed above, the most peculiar sonographicfinding at presentation was the midline oblong anechoicstructure. This feature was explained when MRI showedseparation of the bifid portions of the brainstem,together with its downward displacement (Figure 2).Figure 1 Oblique axial (a) and axial (b) ultrasound images of the fetal head at 26 weeks’ gestation, showing enlargement of the lateralventricles and the third ventricle (*). The cerebellar lobes (arrows) were separated, with no detectable vermian structure. The dotted arrowindicates the retropulvinar cistern. (c) Axial ultrasound image at 35 weeks, showing widening of the midline anechoic structures.Copyright 2009 ISUOG. Published by John Wiley & Sons, Ltd. LETTERS TO THE EDITOR364 Letters to the EditorFigure 2 Single shot fast spin echo T2-weighted magnetic resonance images of the fetal head at 26 weeks. (a,b) Axial planes at differentlevels showing separated cerebellar lobes (solid arrows), bifid pons (arrowhead), third ventricle (*) and retropulvinar cistern (dotted arrow).(c) Sagittal view showing the kinked brainstem (box). The line indicates the plane at which the axial images shown in (b) and in Figures 1band 1c were obtained.Figure 3 Fetal retinal non-attachment at 31 weeks, imaged usingsonography, seen as a conical structure in the sagittal plane (a) andas concentric circles in the coronal plane (b).Figure 4 Magnetic resonance imaging on day 6 of postnatal life,showing severe enlargement of the lateral ventricles and the cisternamagna, together with the typical ‘cobblestone’ appearance of thecortical mantle (a) and abnormal cerebellar gyral pattern (b).The resulting enlarged retropulvinar cistern appeared incontinuation with the enlarged third ventricle anteriorlyand with the communication between the fourth ventricleand the cisterna magna posteriorly. We suggest thatthis characteristic might represent an indirect sign ofmaldevelopment of the brainstem. As it was detectable atan earlier gestational age than ocular anomalies, it mayoffer an earlier sonographic clue leading to suspicion ofthe diagnosis of WWS