Génétique des cardiomyopathies dilatées.

Abstract

Les cardiomyopathies dilatees (CMD) sont caracterisees par une dilatation des cavites cardiaques et une baisse de la contractilite. Il s' agit d' une affection severe pouvant conduire a l' insuffisance cardiaque et a la mort subite et c' est une indication majeure de transplantation cardiaque. Environ 30 % a 40 % des CMD sont d' origine familiale ; le gene codant pour l' actine cardiaque et six locus chromosomiques sont incrimines dans les formes autosomiques dominantes; des deletions, des duplications et des mutations ponctuelles du gene de la dystrophine sont responsables de formes liees a l' X ; il existe une forme autosomique recessive pour laquelle les localisations chromosomiques n' ont pas encore ete determinees. La determination des alterations genetiques a l' origine des CMD permettra une approche rationnelle de la pathologie et l' identification des individus a risque afin de leur apporter un suivi medical pour prevenir la progression de la maladie.

Dilated cardiomyopathy (CMD) is a heart disease characterized by dilation and impaired contraction of the left ventricle or both ventricles. It is a significant health problem regarding the prevalence, the high mortality rates, and the severity of the disease leading to heart failure and sudden death. CMD represents the major indication for heart transplantation. The importance of genetic factors implicated in CMD has been underestimated for a l ong time and CMD molecular genetics is, at the present time, much less documented than in other cardiovascular genetic diseases such as hypertrophic cardiomyopathy. Nevertheless, in the case of familial CMD, which represents about 30-40% of idiopathic CMD, the cardiac actin gene and size distinct chromosomal locations have been already implicated in the case of autosomal dominant pattern of inheritance. Deletions, duplications and mutations in the dystrophin gene are known to be responsible for X-linked CMD. Familial CMD is therefore a heterogeneous disorder, with different patterns of transmission and variable clinical features, since the disease can be associated with conduction defects or/and myopathy. Identification of genes involved in CMD should allow a rational approach to the etiology and pathogenesis of the disease. Finally, the identification of genetically affected individuals, even if they are asymptomatic, should have important clinical implications including medical management and early treatment in order to prevent the progression of the disease.