Molecular genetic diagnostics for ventricular arrhythmias and sudden cardiac death syndromes

Inherited forms of ventricular arrhythmias are rare diseases, but a major cause for severe cardiac events, sudden unexplained death syndromes, and death in young adults, infants, and children. Each disorder is genetically heterogeneous (5-20 genes per disease) and molecular testing may include both core genes and less common disease genes as well. Owing to the rapid development and feasibility of sequencing technologies enabling a parallel analysis of several hundred genes up to a whole exome, disease mutations can be identified very efficiently, but have to be seen in the complexity and natural variance of the human genome. Precise phenotypic knowledge and advanced gene variant interpretation are important to ensure adequate patient diagnostics and management. This article focuses on the genetic causes of inherited arrhythmia forms predisposing patients to sudden cardiac death and discusses practical issues and skills for molecular testing.