Clinical studies in non-chromosome 4-linked facioscapulohumeral muscular dystrophy

Objectives To characterize clinically and molecularly a large, non-chromosome 4-linked facioscapulohumeral muscular dystrophy (FSHMD) family. Methods Neurological evaluations of affected (N = 55) and at-risk (N = 48) individuals were performed along with selected laboratory analyses, including creatine kinase testing, muscle biopsy, p13E-11 fragment analysis, and cytogenetic studies. Genetic analyses of the scapuloperoneal muscular dystrophy and scapuloperoneal muscular atrophy regions on chromosome 12 were performed using genetic markers flanking the intervals of interest and parametric LOD score analyses. Results Clinically, the FSHMD in individuals in this family is indistinguishable from that observed in chromosome 4-linked FSHMD. Fragment analysis with p13E-11 showed no small fragment segregating with the family and no evidence for 4:10 translocation or deletion of the p13E-11 binding site. Linkage analysis excluded the loci for autosomal-dominant scapuloperoneal muscular dystrophy and scapuloperoneal muscular atrophy. Conclusions This family is clinically similar to patients with the chromosome 4-linked FSHMD. These data support our previous hypothesis of genetic heterogeneity within FSHMD.