Abstract

Walker-Warburg syndrome is a rare, lethal congenital diffuse neurodysplasia, characterized by variable cerebral and ocular abnormalities. Cerebral abnormalities include ventriculomegaly, encephalocele, and Dandy-Walker malformation. Other features include varied ocular findings in the posterior or anterior segments of the eye or in both. Principal diagnostic criteria are lissencephaly, cerebellar and ocular abnormalities, and congenital muscular dystrophy. Recurrence of Walker-Warburg syndrome in siblings, especially in consanguineous families, suggests an autosomal recessive mode of inheritance. Several genes have been implicated with considerable heterogeneity. Approximately 20% of patients have mutations in the protein O -mannosyltransferase 1 and 2 ( POMT1 and POMT2 ) genes. Prenatal diagnosis is based on typical ultrasound findings in the setting of a family history of the disorder. Genetic counseling should be offered to parents; amniocentesis should be recommended to exclude aneuploidy and to test for mutations in families that carry known mutations. Clinical manifestations at birth include generalized hypotonia, muscle weakness, developmental delay, mental retardation, and occasional seizures. Laboratory investigations usually show elevated creatine kinase, and muscle pathology reveals a myopathic or dystrophic pattern and altered alpha-dystroglycan. Infants often die within the first few months of life, with almost all affected children dying by age 3 years. No specific treatment is available, and management is supportive and preventive.