Update on genetics of catecholaminergic polymorphic ventricular tachycardia

Abstract

Catecholaminergic polymorphic ventricular tachycardia is a rare genetic cause of sudden cardiac death in the young population. It is characterized by adrenergic-induced bidirectional and polymorphic ventricular tachycardias in patients with structurally normal heart. This lethal arrhythmogenic syndrome is difficult to diagnose due to incomplete penetrance and variable expressivity. Recognition of the characteristic electrocardiogram findings and knowledge of the management of patients are crucial, given the risk of arrhythmia recurrence and cardiac arrest. Early identification of families at risk help to prevent lethal episodes. Currently, nine genes have been associated with the disease (ANK2, CALM1, CALM2, CALM3, CASQ2, KCNJ2, RyR2, TECRL, and TRDN), following an autosomal dominant or recessive pattern of inheritance. The main gene related to the disease is RyR2, which encodes the cardiac ryanodine receptor 2, and underlies 60% of all cases. A large part of current genetic variants reported remains classified as of uncertain significance, impeding a conclusive translation into clinical practice. In this review, we discuss the main clinical characteristics and current advances in genetic basis of catecholaminergic polymorphic ventricular tachycardia.