Concealed Arrhythmogenic Right Ventricular Cardiomyopathy in Sudden Unexplained Cardiac Death Events

lakophilin-2 (PKP2) is an integral component of the desmosome, important in cell-cell adhesion. Causative variants in PKP2 are a well-established cause of arrhythmogenic right ventricular cardiomyopathy (ARVC). An inherited cardiomyopathy characterized by fibro-fatty replacement of the myocardium and propensity for ventricular arrhythmias. Importantly, sustained arrhythmias have been shown only to occur in mutation carriers with clear structural disease on imaging. 1 PKP2 is important for transcription of genes that control intracellular calcium cycling, and it is hypothesized this newly described disease mechanism could lead to life-threatening arrhythmias in humans in the absence of structural disease. 2 Despite this, the arrhythmic risk is not reported before the development of an overt phenotype. We report 4 unrelated probands who presented because of an unexplained sudden cardiac arrest with overt structurally normal hearts in early adulthood with causative loss of function variants in the PKP2 gene subsequently identified.