Clinical and genetic distinction between Walker-Warburg syndrome and muscle-eye-brain disease

B. Cormand, H. Pihko, M. Bayés, L. Valanne, P. Santavuori, B. Talim, R. Gershoni-Baruch, A. Ahmad, H. Van Bokhoven, H. G. Brunner, T. Voit, H. Topaloglu, W. B. Dobyns, A. E. Lehesjoki

Research output: Contribution to journalArticlepeer-review

140 Scopus citations


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. Objectives: 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. Conclusion: 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).

Original languageEnglish (US)
Pages (from-to)1059-1069
Number of pages11
Issue number8
StatePublished - Apr 24 2001
Externally publishedYes


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