Rippling muscle disease and cardiomyopathy associated with a mutation in the CAV3 gene.
Caveolin-3, the myocyte-specific isoform of caveolins, is preferentially expressed in skeletal, cardiac and smooth muscles. Mutations in the CAV3 gene cause clinically heterogeneous neuromuscular disorders, including rippling muscle disease, or cardiopathies. The same mutation may lead to different phenotypes, but cardiac and muscle involvement rarely coexists suggesting that the molecular network acting with caveolin-3 in skeletal muscle and heart may differ. Here we describe an Italian family (a father and his two sons) with clinical and neurophysiological features of rippling muscle disease and heart involvement characterized by atrio-ventricular conduction defects and dilated cardiomyopathy. Muscle biopsy showed loss of caveolin-3 immunosignal. Molecular studies identified the p.A46V mutation in CAV3 previously reported in a German family with autosomal dominant rippling muscle disease and sudden death in few individuals. We suggest that cardiac dysfunction in myopathic patients with CAV3 mutations may be underestimated and recommend a more thorough evaluation for the presence of cardiomyopathy and potentially lethal arrhythmias.
Department of Neuroscience, Institute of Neurology, Catholic University, Largo Agostino Gemelli 8, 00168 Rome, Italy.
Michela
M
Catteruccia
Tommaso
T
Sanna
Filippo Maria
FM
Santorelli
Alessandra
A
Tessa
Raffaella
R
Di Giacopo
Donato
D
Sauchelli
Alessandro
A
Verbo
Mauro
M
Lo Monaco
Serenella
S
Servidei
D000328:Adult; D000409:Alanine / Q000235:genetics; D009202:Cardiomyopathies / Q000150:complications / Q000235:genetics* / Q000473:pathology; D051244:Caveolin 3 / Q000235:genetics*; D004562:Electrocardiography / Q000379:methods; D004576:Electromyography / Q000379:methods; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology; D009135:Muscular Diseases / Q000150:complications / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D014633:Valine / Q000235:genetics; D055815:Young Adult
D051244:Caveolin 3; D014633:Valine; D000409:Alanine