Genetics, manifestations, and management of catecholaminergic polymorphic ventricular tachycardia

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a devastating heritable channelopathy that can lead to sudden cardiac death in children and young adults. This review aims to explore genetics, the cardiac and extracardiac manifestations of mutations associated with CPVT, and the challenges involved with managing phenotypically variable variants.

The understanding of the genetics and mechanisms of CPVT continues to grow with recent discoveries including alternative splicing of cardiac TRDN and calmodulin gene variants. Additionally, there is an increasing recognition of the extra-cardiac manifestations such as epilepsy, neurodevelopmental delay, and glucose homeostasis abnormalities in RyR2 variant carriers. Advances in precision medicine, including the development of iPSC-derived cardiomyocytes, are valuable models for developing targeted therapeutics.

CPVT remains a complex disorder with cardiac and neurological manifestations impacting management. Early genetic testing and personalized treatment, including beta-blockers, flecainide, and ICDs, is important in improving outcomes. Ongoing research into the mechanism of each mutation will help in developing more effective, personalized therapeutics.