Home > D. Systemic pathology > Genetic and developmental anomalies > Walker-Warburg syndrome

Walker-Warburg syndrome

Thursday 16 October 2003

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)