Genetic Determinants of Inherited Cardiac Arrhythmias

Inherited cardiac arrhythmias are a major cause of sudden cardiac death in individuals without structural heart disease. These conditions are primarily genetic, resulting from pathogenic variants affecting cardiac ion channels, calcium-handling proteins, intercellular junctions, and transcriptional regulators. While research has traditionally focused on ventricular syndromes such as long QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia, atrial fibrillation-particularly early-onset disease-has been increasingly recognized as heritable, especially when affecting young individuals. Advances in molecular genetics have improved diagnosis, risk stratification, and family screening in these diseases as well as the possibility of postmortem evaluation of sudden unexplained death. This review summarizes the genetic basis and clinical implications of these inherited cardiac arrhythmias.