Muscular Dystrophy, Congenital, Merosin-Positive

Clinical Features

Mahjneh et al. (1992) reported a large consanguineous Palestinian family in which 10 individuals had congenital muscular dystrophy with generalized muscle weakness and hypotonia since birth, but without arthrogryposis or central nervous system involvement. Interestingly, 9 additional family members had adult-onset limb-girdle muscular dystrophy type 2B (253601) caused by mutation in the gene encoding dysferlin (DYSF; 603009.0006); the patients with congenital muscular dystrophy did not have the DYSF mutation (Bashir et al., 1998). Mahjneh et al. (1999) and Sellick et al. (2005) provided additional clinical information on the family reported by Mahjneh et al. (1992). The pattern of muscle weakness and wasting in the patients with congenital muscular dystrophy was more marked in the proximal upper limb-girdle and trunk muscles. Lower limb muscles were mildly involved. Muscle biopsy showed a dystrophic pattern with normal staining for dystrophin (300377), laminin alpha-2 of merosin (156225), and the sarcoglycans (see, e.g., SGCA; 600119).

Mapping

By genomewide analysis of a large consanguineous Palestinian family with merosin-positive CMD, Sellick et al. (2005) identified a candidate disease locus on chromosome 4p16.3. Combined data from both a high-density SNP array and microsatellite markers delineated a 4.14-Mb interval flanked centromerically by marker D4S432 (multipoint lod score of 3.4). Mutations in the SPON2 (605918) and MYL5 (160782) genes were excluded.