Three siblings with Walker-Warburg Syndrome.

The Walker-Warburg syndrome (WWS) is an autosomal recessive disease entity within the framework of "cerebro-ocular-muscular syndromes". The gene locus is still undetected. Its diagnostic criteria have been firmly established in the literature on newborns or infants affected with the disease. However, a diagnosis of severe pathologic conditions must often be made on the basis of ultrasound examination at a fetal age. It is therefore necessary to examined whether the diagnostic criteria are sufficient to warrant a diagnosis at the fetal stage. We here report on a new family affected with WWS. Two elder siblings had presented with epileptic seizures, eye abnormalities as well as multiple skeletal dysplasias (the latter finding in the first child only) in the neonatal period, and died in their first years. Postmortem examination of the second child revealed type II lissencephaly, buphthalmos, and undifferentiated retina with rigid retinal folds. Skeletal muscle tissue was not examined. In a sibling fetus, bilateral cataract was detected in the 17th gestational week by ultrasonographic examination. Postmortem examination in the 23rd gestational week revealed type II lissencephaly and bilateral cataract. Skeletal muscle was normal. Taken together, all siblings were diagnosed as Walker-Warburg syndrome. In the fetal case, prenatal diagnosis could only be made with confidence against a background of a positive family history.