Myopathy, Distal, 3

Clinical Features

Mahjneh et al. (2003) reported a large Finnish family in which 7 individuals spanning 4 generations developed slowly progressive adult-onset distal myopathy. Age at onset ranged from 32 to 45 years with clumsiness in the hands and/or feet. Later features included steppage gait due to marked weakness of ankle dorsiflexion, contractures of the hands leading to claw hands, and weakness and wasting of the intrinsic hand muscles. Lower limb muscle weakness tended to be asymmetric. MRI showed fatty degeneration of affected muscles. Proximal muscle involvement occurred later in the disease. EMG showed myopathic changes. Serum creatine kinase was normal or slightly increased, and muscle biopsy showed severe dystrophic changes with rimmed vacuoles. Cardiac and respiratory functions were not affected. There was no evidence of linkage to Welander distal myopathy (WDM; 604454) or tibial muscular dystrophy (TMD; 600334).

Inheritance

The transmission pattern of MPD in the family reported by Mahjneh et al. (2003) was consistent with autosomal dominant inheritance.

Mapping

By genomewide analysis of the family reported by Mahjneh et al. (2003), Haravuori et al. (2004) found significant linkage to 2 distinct regions on chromosomes 8p22-q11 and 12q13-q22 (maximum multipoint lod score of 3.01 for both regions). Haravuori et al. (2004) concluded that the defective gene in this family is located on either chromosome 8 or 12, or that both loci are involved, possibly representing digenic inheritance. Sequencing excluded pathogenic mutations in the coding regions of the ANK1 (612641) and MLC1SA (609930) genes on 8p11 and 12q13, respectively.