Dilated cardiomyopathy (DCM) is the most common form of cardiomyopathy, which is responsible for more than 2.85 million cases of heart failure, and causes approximately 25,000 deaths every year in the United States. Characteristic features of DCM are an enlargement of the left ventricle, with systolic dysfunction and a reduction in the force of contraction. Symptoms at initial presentation of DCM often include heart failure, arrhythmias and/or conduction system disease, and/or thromboembolic disease. Both nongenetic and genetic factors can cause DCM. The nongenetic factors may include ischemia, toxins, infections, endocrine dysfunction, inflammatory conditions, protracted hypertension, metabolic disturbances, and radiation. The 50% of DCM patients in whom an underlying cause is not apparent are said to have idiopathic DCM (IDC). IDC is not always
symptomatic and the initial symptom may be sudden cardiac death (SCD). Preventative cardiac screening can be used to detect some individuals with IDC that are asymptomatic. When 2 or more individuals in the same family are found to have DCM, this is classified as familial DCM (FDC). The mean age at onset and clinical characteristics of FDC can be highly variable even within the same family. Clinical genetic testing is available in the United States for 41 genes that have been linked with DCM, although in most of these genes, sequence variants are rare among DCM patients. In addition, sequence variants in many of the same genes are associated with other forms of cardiomyopathy, as well as other clinically distinct disorders such as some forms of muscular dystrophy. Many of the genes associated with DCM encode for proteins that function as part of the sarcomere. The sarcomere is the structural and functional unit of muscle and is composed of thick and thin filaments that slide past one another during muscle contraction. The inheritance of FDC is mostly autosomal dominant, but cases of X-linked, mitochondrial, and autosomal recessive inheritance may account for up to 10% of FDC.