Danna A Spears, Michael H Gollob

A sudden unexplained death is felt to be due to a primary arrhythmic disorder when no structural heart disease is found on autopsy, and there is no preceding documentation of heart disease. In these cases, death is presumed to be secondary to a lethal and potentially heritable abnormality of cardiac ion channel function. These channelopathies include congenital long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome, and short QT syndrome. In certain cases, genetic testing may have an important role in supporting a diagnosis of a primary arrhythmia disorder, and can also provide prognostic information, but by far the greatest strength of genetic testing lies in the screening of family members, who may be at risk. The purpose of this review is to describe the basic genetic and molecular pathophysiology of the primary inherited arrhythmia disorders, and to outline a rational approach to genetic testing, management, and family screening.