A newly recognized autosomal dominant limb girdle muscular dystrophy with cardiac involvement

Abstract

Sixty-five members of three families with limb girdle muscular dystrophy (LGMD) underwent neurological, cardiological, and ancillary investigations. Thirty-five individuals were diagnosed as having slowly progressive autosomal dominant LGMD. Symmetrical weakness started in the proximal lower limb muscles, and gradually upper limb muscles also became affected. Early contractures of the spine were absent. Contractures of elbows and Achilles tendons were either minimal or late. Serum creatine kinase activity was normal to moderately elevated. Electromyogram and muscle biopsy were consistent with a mild muscular dystrophy. Cardiological abnormalities, found in more than one-half the patients, included dysrhythmias and atrioventricular (AV) conduction disturbances presenting as bradycardia, syncopal attacks necessitating pacemaker implantation, and sudden cardiac death. There was a significant relation between the severity of AV conduction disturbances and age. In nearly all patients, neuromuscular symptomatology preceded cardiological involvement. The early recognition of this previously not described, autosomal dominant LGMD with life-threatening cardiac involvement offers an opportunity for therapeutic intervention.

Identification of lamin A/C (LMNA) gene mutations in Korean patients with autosomal dominant Emery-Dreifuss muscular dystrophy and limb-girdle muscular dystrophy 1B

“…They showed similar clinical features with slowly progressive limb-girdle weakness, the absence of early contractures, age-related atrioventricular cardiac conduction disturbance, and dilated cardiomyopathy (van der Kooi et al 1996;Muchir et al 2000;Kitaguchi et al 2001). Our patient in the present study was also a familial case and showed very similar clinical features as described previously.…”

“…On the other hand, LGMD1B is slowly progressive, with age-related atrioventricular (AV) cardiac conduction disturbance, dilated cardiomyopathy, and the absence of early contractures (van der Kooi et al 1996).…”

A new form of autosomal dominant limb-girdle muscular dystrophy (LGMD1G) with progressive fingers and toes flexion limitation maps to chromosome 4p21

“…6 LGMD1A is caused by a defect in the myotilin gene. 7 LGMD1B, located at 1q11, 8 is caused by a defect in lamin A/C 9 and LGMD1C, located at 3p25, is caused by deficiency in caveolin-3. 10,11 The locus for LGMD1D, LGMD1E and LGMD1F are respectively located at 7q, 12 6q23 13 and 7q32, 14 but their genes were not yet identified.…”

A new locus on 3p23–p25 for an autosomal-dominant limb-girdle muscular dystrophy, LGMD1H

“…2 LGMD1B, due to mutations in LMNA gene encoding lamin A/C on chromosome 1q21, and LGMD1E, on 6q23, are also associated with heart conduction system abnormalities, including atrio-ventricular blocks, arrhythmia, and sudden death. [3][4][5] Mutations in CAV3 gene, located on chromosome 3p25 (LGMD1D), encoding caveolin are associated with high creatine kinase (CK) levels with normal strength and distal myopathy, and usually occur in early childhood. 6 Both LGMD1D 7 and LGMD1F 8,9 loci map to chromosome 7q and do not present distinctive clinical features.…”

“…10 Fewer than ten AD-LGMD families show allelism with Bethlem myopathy mapped to chromosomes 2q37 and 21q22. 3 and, less frequently, with facioscapulohumeral dystrophy (FSHD) mapped to 4q35 locus (www.neuro.wustl.edu/neuromuscular/musdist/ lg.html). Pedigrees not linked to any of the listed loci warrant further genetic heterogeneity.…”