Challenges in the prenatal diagnosis of Walker-Warburg syndrome. P.G. Wheeler¹, D. Levine², T.L. Stewart¹, D.W. Bianchi¹. 1) Division of Genetics, Department of Pediatrics, Tufts University School of Medicine, Boston, MA; 2) Dept. of Radiology,Beth Israel Deaconess Medical Center, Boston, MA.

   Walker-Warburg syndrome is an autosomal recessive condition involving anomalies of the brain(lissencephaly and other structural defects), eye(cataracts and anterior chamber defects) and muscular dystrophy. We have recently had a case that highlights the difficulties and importance of making this diagnosis.
   Abnormalities in the 1st pregnancy of a 33-year-old woman were first detected at 33 weeks' gestation when a prenatal ultrasound examination was performed for maternal concerns of decreased fetal movement. It showed marked hydrocephalus, cerebellar hypoplasia, and possible club feet. Fetal head MRI showed severe hydrocephalus,porencephaly,a non-dilated 4th ventricle, and cerebellar hypoplasia. The corpus callosum was not visualized. The preliminary diagnosis was cerebro-cerebellar dysplasia with porencephaly. Delivery occurred at 34 weeks. At birth, multiple joint contractures and minimal muscle mass were noted. The neonate died at 1 day of age from respiratory failure. At autopsy, partial lissencephaly, hydrocephalus and absence of the corpus callosum were detected. A muscle biopsy done shortly after death found abnormalities consistent with a congenital muscular dystrophy. Examination of the eyes revealed early sub-capsular cataracts. These findings are consistent with the diagnosis of Walker-Warburg syndrome.
   The diagnosis of Walker-Warburg syndrome in the baby highlights several important factors, including that this diagnosis typically can not be made based on fetal ultrasound or fetal head MRI alone, since neither study generally detects the lissencephaly seen in this condition. Also, without a complete autopsy (including muscle pathology and eye dissection) the diagnosis of Walker-Warburg syndrome cannot be made accurately when it is the first presentation in the family. The accurate diagnosis of this condition is essential since as an autosomal recessive condition it has a 25% recurrence risk, which is considerably different than the neglible recurrence risk for porencephaly.