Clinical Information

The cardiomyopathies are a group of disorders characterized by disease of the heart muscle. Cardiomyopathy can be caused by inherited, genetic factors or by nongenetic (acquired) causes such as infection and inflammation.(1) When the presence or severity of the cardiomyopathy observed in a patient cannot be explained by acquired causes, genetic testing for the inherited forms of cardiomyopathy may be considered.

Hereditary forms of dilated cardiomyopathy (DCM) are characterized by ventricular dilation with reduced cardiac performance in the absence of other cardiac or systemic causes that may cause dilation of the heart muscle, such as hypertension and ischemic heart disease. The incidence of DCM in the general population is approximately 1 in 2500 (1), and it is estimated that approximately 50% of cases can be attributed to a genetic etiology.(1) Hereditary forms of DCM are most often caused by genes encoding proteins of the cardiac cytoskeleton and sarcomere.

Left ventricular noncompaction (LVNC) is characterized by prominent trabeculations of the left ventricle with trabecular recesses extending into the ventricular cavity. The incidence of LVNC in the general population is estimated to be 1 in 5000.(2) It is currently unclear if LVNC represents a genetically distinct form of cardiomyopathy, as many familial cases of LVNC have been linked to the same genes associated with other forms of hereditary cardiomyopathies, and many affected individuals also meet diagnostic criteria for DCM or hypertrophic cardiomyopathy.(2,3)

The clinical presentation of DCM and LVNC can be variable, even within the same family. DCM and LVNC can be apparently asymptomatic in some individuals but can cause sudden, life-threatening arrhythmias, increasing the risk of sudden cardiac death. In addition, some patients with primary hypertrophic cardiomyopathy or arrhythmogenic cardiomyopathy may eventually develop dilated ventricles, resembling DCM in later stages of disease progression.(1) DCM may also be a feature of an underlying systemic disorder such as amyloidoses and musculoskeletal conditions.(1)

Hereditary forms of DCM and LVNC can follow an autosomal dominant, autosomal recessive, and X-linked patterns of inheritance. Mitochondrial inheritance is also possible, however, genes associated with mitochondrial inheritance of DCM and LNVC are not assessed on this panel.