title: Clinical and genetic distinction between Walker-Warburg syndrome and muscle-eye-brain disease.
abstract: BACKGROUND
  Three rare autosomal recessive disorders share the combination of congenital muscular dystrophy and brain malformations including a neuronal migration defect: muscle-eye-brain disease (MEB), Walker-Warburg syndrome (WWS), and Fukuyama congenital muscular dystrophy (FCMD). In addition, ocular abnormalities are a constant feature in MEB and WWS. Lack of consistent ocular abnormalities in FCMD has allowed a clear clinical demarcation of this syndrome, whereas the phenotypic distinction between MEB and WWS has remained controversial. The MEB gene is located on chromosome 1p32-p34.
  
  
  OBJECTIVE
  To establish distinguishing diagnostic criteria for MEB and WWS and to determine whether MEB and WWS are allelic disorders.
  
  
  METHODS
  The authors undertook clinical characterization followed by linkage analysis in 19 MEB/WWS families with 29 affected individuals. With use of clinical diagnostic criteria based on Finnish patients with MEB, each patient was categorized as having either MEB or WWS. A linkage and haplotype analysis using 10 markers spanning the MEB locus was performed on the entire family resource.
  
  
  RESULTS
  Patients in 11 families were classified as having MEB and in 8 families as WWS. Strong evidence in favor of genetic heterogeneity was obtained in the 19 families. There was evidence for linkage to 1p32-p34 in all but 1 of the 11 pedigrees segregating the MEB phenotype. In contrast, linkage to the MEB locus was excluded in seven of eight of the WWS families.
  
  
  CONCLUSIONS
  These results allow the classification of MEB and WWS as distinct disorders on both clinical and genetic grounds and provide a basis for the mapping of the WWS gene(s).
authors.affiliation: Department of Medical Genetics, University of Helsinki, Finland. bcormand@imim.es
authors.forename: B
authors.initials: B
authors.lastname: Cormand
authors.forename: H
authors.initials: H
authors.lastname: Pihko
authors.forename: M
authors.initials: M
authors.lastname: Bayés
authors.forename: L
authors.initials: L
authors.lastname: Valanne
authors.forename: P
authors.initials: P
authors.lastname: Santavuori
authors.forename: B
authors.initials: B
authors.lastname: Talim
authors.forename: R
authors.initials: R
authors.lastname: Gershoni-Baruch
authors.forename: A
authors.initials: A
authors.lastname: Ahmad
authors.forename: H
authors.initials: H
authors.lastname: van Bokhoven
authors.forename: H G
authors.initials: HG
authors.lastname: Brunner
authors.forename: T
authors.initials: T
authors.lastname: Voit
authors.forename: H
authors.initials: H
authors.lastname: Topaloglu
authors.forename: W B
authors.initials: WB
authors.lastname: Dobyns
authors.forename: A E
authors.initials: AE
authors.lastname: Lehesjoki
mesh_terms: D000293:Adolescent; D001921:Brain / Q000002:abnormalities*; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D003616:Dandy-Walker Syndrome / Q000175:diagnosis / Q000235:genetics*; D005124:Eye Abnormalities / Q000175:diagnosis / Q000235:genetics*; D015785:Eye Diseases, Hereditary / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007223:Infant; D008126:Lod Score; D008297:Male; D009136:Muscular Dystrophies / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype