Genetics of familial cardiomyopathies and arrhythmias

Molecular cardiology has become an important tool in understanding the aetiology, pathogenesis and development of familial cardiomyopathies and arrhythmias. The knowledge of genotype-phenotype correlations in certain pathologies has changed the concepts of therapy. In monogenic diseases, genetic testing offers a new complementary diagnostic approach. A genetic test can be used to confirm a clinically determined diagnosis, predict prognosis in a clinically affected patient, or provide options for therapy in patients and in clinically unaffected relatives of a patient with the disease producing mutation. In pure forms of familial hypertrophic cardiomyopathy mutations in several genes coding for sarcomeric proteins have been identified, indicating wide locus heterogeneity. Various disease genes are implicated in familial dilated cardiomyopathy in the pure form or in combination with other diseases. In the long QT syndrome and Brugada syndrome, mutations in ion channel genes can cause the disease; one of those genes is also implicated in progressive cardiac conduction defect. In other familial diseases like the arrhythmogenic right ventricular cardiomyopathy, anyone of the numerous chromosomal loci can be involved, but only one gene has been identified so far. The same gene is also involved in catecholaminergic polymorphic ventricular tachycardia. From genotype-phenotype studies, correlations between gene-mutations and the clinical course of the disease have become clear. As only a few families with the same mutations have been studied, data have to be considered as preliminary and any conclusion must be regarded as tentative. This emphasizes the need to study genotype-phenotype correlations in a large number of families.