Walker-Warburg syndrome (WWS) is an autosomal recessive developmental disorder characterized by congenital muscular dystrophy and complex brain and eye abnormalities.

A similar combination of symptoms is presented by two other human diseases, muscle-eye-brain disease (MEB) and Fukuyama congenital muscular dystrophy (FCMD).

Synopsis

 craniofacial anomalies

• microcephaly
• microtia
• absent auditory canals
• ceft lip / cleft palate

 ocular anomalies

• retinal detachment
• cataract
• microphthalmia
• retinal malformations
• anterior chamber malformation
• hyperplastic primary vitreous
• optic nerve hypoplasia
• coloboma
• glaucoma
• Peters anomaly

 iperforate anus
 genital abnormalities
 renal dysplasia

 limbs

• congenital contractures
• muscular dystrophy
• muscle biopsy shows defective glycosylation of alpha-dystroglycan (DAG1, 128239)

 cerebrospinal anomalies

• hypotonia
• delayed development
• ayria
• hydrocephalus
• occipital encephalocele
• meningoencephalocele
• type II lissencephaly
• disorganized brain cytoarchitecture
• cerebellar malformation
• macrogyria and/or polymicrogyria
• Dandy-Walker malformation
• ventriculomegaly
• elevated serum creatine kinase

Etiology

 mutations in

• the O-mannosyltransferase gene POMT1 (#12369018#)
• the O-mannosyltransferase gene POMT2

 A phenotype consistent with Walker-Warburg syndrome has been shown to be caused by mutation in the fukutin gene (MIM.607440), the same gene that causes the less severe Fukuyama congenital muscular dystrophy (FCMD) (MIM.253800)