Walker-Warburg Syndrome (WWS) is a rare form of autosomal recessive congenital
muscular dystrophy associated with brain and
eye abnormalities. WWS has a worldwide distribution. The overall incidence is unknown but a survey in North-eastern Italy has reported an incidence rate of 1.2 per 100,000 live births. It is the most severe form of congenital
muscular dystrophy with most children dying before the age of three years. WWS presents at birth with generalized
hypotonia, muscle weakness, developmental delay with
mental retardation and occasional
seizures. It is associated with type II
cobblestone lissencephaly,
hydrocephalus, cerebellar malformations,
eye abnormalities and congenital
muscular dystrophy characterized by hypoglycosylation of
alpha-dystroglycan. Several genes have been implicated in the etiology of WWS, and others are as yet unknown. Several mutations were found in the
Protein O-Mannosyltransferase 1 and 2 (POMT1 and POMT2) genes, and one mutation was found in each of the fukutin and fukutin-related
protein (FKRP) genes. Laboratory investigations usually show elevated
creatine kinase, myopathic/dystrophic muscle pathology and altered
alpha-dystroglycan. Antenatal diagnosis is possible in families with known mutations. Prenatal ultrasound may be helpful for diagnosis in families where the molecular defect is unknown. No specific treatment is available. Management is only supportive and preventive.