Clinical and molecular studies in a unique family with autosomal dominant limb-girdle muscular dystrophy and Paget disease of bone.
OBJECTIVE
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, biochemical and radiologic evaluations were performed to delineate clinical features of the disorder. Linkage analysis with polymorphic markers was performed for 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 with 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 weakness, and respiratory and cardiac failure in their 40s-60s. Linkage analysis excluded autosomal dominant and recessive LGMD, PDB, and cardiomyopathy loci.


CONCLUSIONS
Autosomal dominant LGMD associated with PDB is an unusual disorder. Linkage analysis indicates a unique locus in this family.
Department of Pediatircs, Southern Illinois University-School of Medicine, Springfield 62794-9658, USA.
V E
VE
Kimonis
M J
MJ
Kovach
B
B
Waggoner
S
S
Leal
A
A
Salam
L
L
Rimer
K
K
Davis
R
R
Khardori
D
D
Gelber
D000328:Adult; D017668:Age of Onset; D000368:Aged; D001706:Biopsy; D002311:Cardiomyopathy, Dilated / Q000235:genetics; D005192:Family Health; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology; D009136:Muscular Dystrophies / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics*; D010001:Osteitis Deformans / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics*; D010375:Pedigree; D011110:Polymorphism, Genetic; D011859:Radiography
D005819:Genetic Markers