Genetics of inherited cardiomyopathies

Abstract

Cardiomyopathies are the most common disorders resulting in heart failure, with dilated cardiomyopathy being responsible for the majority of cases. Other forms of cardiomyopathy, especially hypertrophic forms, are also important causes of heart failure. The mortality rate due to cardiomyopathy in the USA is over 10,000 deaths per year, and the costs associated with heart failure are approximately 200 million US dollars per year in the USA alone. Over the past few years, breakthroughs have occurred in understanding the basic mechanisms of these disorders, potentially enabling clinicians to devise improved diagnostic strategies and therapies. As at least 30 to 40% of cases are inherited, it is now imperative that the genetic basis for these disorders is clearly recognized by caregivers and scientists. However, it has also become clear that these diseases are genetically highly heterogeneous, with multiple genes identified for each of the major forms of cardiomyopathy, and most patients having private mutations. These data suggest that the genetic diagnosis of most patients with cardiomyopathy will be impractical with current technologies. However, there are a few exceptions, such as patients with X-linked cardiomyopathies, with or without the concomitant abnormalities of cyclic neutropenia and 3-methylglutaconic aciduria, or patients with cardiomyopathy associated with conduction disease: these appear to be associated with mutations in a small subset of genes, and can be investigated by certified diagnostic laboratories. This review will summarize current knowledge of the genetics of inherited cardiomyopathies and how findings from research laboratories may be translated into the diagnostic laboratory.