Definition: 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
imperforate 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
- type II lissencephaly
- disorganized brain cytoarchitecture
- cerebellar malformation
- macrogyria and/or polymicrogyria
- Dandy-Walker malformation
- ventriculomegaly
- elevated serum creatine kinase
-
neural tube defects
- occipital encephalocele
- meningoencephalocele
Etiology
germline mutations in
- the O-mannosyltransferase gene POMT1 (12369018)
- the O-mannosyltransferase gene POMT2
- the FKTN gene coding for fukutin (MIM.607440) (also causing the Fukuyama congenital muscular dystrophy (FCMD) - MIM.253800)