Diagnostic criteria for Walker-Warburg syndrome

Am J Med Genet. 1989 Feb;32(2):195-210. doi: 10.1002/ajmg.1320320213.

Abstract

Walker-Warburg syndrome (WWS) is an autosomal recessive disorder manifest by characteristic brain and eye malformations. We reviewed data on 21 of our patients and an additional 42 patients from the literature. From this review, we expand the phenotype to include congenital muscular dystrophy (CMD) and cleft lip and/or palate (CLP), and revise the diagnostic criteria. Four abnormalities were present in all patients checked for these anomalies: type II lissencephaly (21/21), cerebellar malformation (20/20), retinal malformation (18/18), and CMD (14/14). We propose that these comprise necessary and sufficient diagnostic criteria for WWS. Two other frequently observed abnormalities, ventricular dilatation with or without hydrocephalus (20/21) and anterior chamber malformation (16/21), are helpful but not necessary diagnostic criteria because they were not constant. All other abnormalities occurred less frequently. Congenital macrocephaly with hydrocephalus (11/19) was more common than congenital microcephaly (3/19). Dandy-Walker malformation (10/19) was sometimes associated with posterior cephalocele (5/21). Additional abnormalities included slit-like ventricles (1/21), microphthalmia (8/21), ocular colobomas (3/15), congenital cataracts (7/20), genital anomalies in males (5/8), and CLP (4/21). Median survival in our series was 9 months. A related autosomal recessive disorder, Fukuyama congenital muscular dystrophy, consists of similar but less severe brain changes and CMD. It differs from WWS because of consistently less frequent and severe cerebellar and retinal abnormalities. We think that WWS is identical to "cerebro-oculo-muscular syndrome" and "muscle, eye, and brain disease."

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / abnormalities*
  • Cerebellum / abnormalities
  • Cerebral Ventricles / abnormalities
  • Chromosome Aberrations / genetics*
  • Chromosome Disorders
  • Cleft Lip / genetics
  • Cleft Palate / genetics
  • Encephalocele / genetics
  • Eye Abnormalities*
  • Female
  • Genes, Recessive*
  • Humans
  • Hydrocephalus / genetics
  • Infant
  • Male
  • Muscular Dystrophies / genetics*
  • Syndrome