Ve. Kimonis et al., Clinical and molecular studies in a unique family with autosomal dominant limb-girdle muscular dystrophy and Paget disease of bone, GENET MED, 2(4), 2000, pp. 232-241
Purpose: To characterize the clinical features and perform linkage analysis
of candidate loci in a large Illinois family with autosomal dominant limb-
girdle muscular dystrophy (LGMD) and Paget disease of bone (PDB). Methods:
The family includes 11 affected individuals (8 M, 3 F). Clinical, biochemic
al and radiologic evaluations were performed to delineate clinical features
of the disorder. Linkage analysis with polymorphic markers was performed f
or previously identified LGMD, PDB and cardiomyopathy loci. Results: Onset
of PDB is early, at a mean age of 35 y, with classic distribution involving
the spine, pelvis, and skull. Muscle weakness and atrophy is progressive w
ith mildly elevated to normal creatine phosphokinase levels. Muscle biopsy
in the oldest male revealed vacuolated fibers, however, in others revealed
nonspecific myopathy. Affected individuals die from progressive muscle weak
ness, and respiratory and cardiac failure in their 40s-60s. Linkage analysi
s excluded autosomal dominant and recessive LGMD, PDB, and cardiomyopathy l
oci. Conclusion: Autosomal dominant LGMD associated with PDB is an unusual
disorder. Linkage analysis indicates a unique locus in this family.