Clinical Information

Sudden cardiac death (SCD) is estimated to occur at an incidence of between 50 to 100 per 100,000 individuals in North America and Europe each year, claiming between 250,000 and 450,000 lives in the United States annually. In younger individuals (15-35 years of age), the incidence of SCD is between 1 to 2 per 100,000 young individuals. Sudden cardiac death, particularly in young individuals, may suggest an inherited form of heart disease. In some cases of SCD, autopsy may identify a structural abnormality, such as a form of cardiomyopathy. In cases with no identified structural abnormality, a hereditary arrhythmia may be suspected. Postmortem diagnosis of a hereditary arrhythmia or cardiomyopathy may assist in confirmation of the cause and manner of death, as well as risk assessment in living family members.

Cardiomyopathies are a group of disorders characterized by disease of the heart muscle. Cardiomyopathy can be caused by either inherited, genetic factors or nongenetic (acquired) causes, such as infection or trauma. 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. Overall, cardiomyopathies are some of the most common genetic disorders. The inherited forms of cardiomyopathy include hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC or AC), and left ventricular noncompaction (LVNC).(1)

Cardiac arrhythmias are a group of conditions characterized by abnormal heart rhythms. Arrhythmias can be caused by either genetic (inherited) factors or nongenetic (acquired) causes, such as medications and infection. Hereditary forms of cardiac arrhythmias assessed for on this panel include, but are not limited to, long QT syndrome, short QT syndrome, catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome, arrhythmogenic right ventricular cardiomyopathy, and familial atrial fibrillation.(2) This panel also assesses genes associated with rarer, syndromic conditions in which cardiac arrhythmia is a major feature, such as Andersen-Tawil syndrome, Carvajal syndrome, Jervell and Lange-Nielsen syndrome, Naxos disease, Timothy syndrome, and Emery-Dreifuss muscular dystrophy.(2-4)

Inherited cardiomyopathies and cardiac arrhythmias can follow autosomal dominant, autosomal recessive, X-linked, and digenic patterns of inheritance. Genes associated with mitochondrial inheritance of cardiomyopathies and cardiac arrhythmias are not assessed on this panel.