Prenatal diagnosis of Walker-Warburg syndrome in three sibs

Walker-Warburg syndrome (WWS) is an autosomal recessive condition characterized by diffuse neurodysplasia, resulting in brain and eye abnormalities. We report on 3 prenatally diagnosed cases of this syndrome born to a consanguineous couple. An ultrasonographic examination showed hydrocephalus at the 27th week of the first pregnancy. Amniocentesis documented a normal male karyotype. The couple opted for termination of the pregnancy but declined an autopsy. Seven months later, hydrocephalus was observed at 20 weeks of the second pregnancy. Termination of pregnancy was performed at the 22nd week. Autopsy of this male fetus showed dilated ventricles, thin cortex, and type II lissencephaly with microscopic evidence of chaotic architecture. Eye examination showed retinal dysplasia. Notwithstanding the lack of demonstrable muscle change, the diagnosis of Walker-Warburg syndrome was made. Ten months later, hydrocephalus was discovered in the third fetus, a female, at 13 weeks of gestation. Termination of pregnancy was performed at 20 weeks. At autopsy, brain, eye, and muscular findings were similar to those of the previous case. In addition, cystic changes and a stenosis of the pyelo-ureteral junction were found in the right kidney. Type II lissencephaly and retinal dysplasia are characteristic of WWS. Muscular dystrophy has been pointed out as an additional abnormality in postnatal cases. By contrast, the lack of demonstrable muscle changes in the fetal period must be emphasized. Those cases illustrate practical problems in the ultrasound and pathologic diagnosis of WWS in the fetal period.