Calcium Release Deficiency Syndrome: A New Inherited Arrhythmia Syndrome

Abstract

Calcium release deficiency syndrome (CRDS) is a newly described form of inherited arrhythmia caused by damaging loss-of-function variants in the cardiac ryanodine receptor (RyR2). Unlike the prototypical RyR2 gain-of-function channelopathy, known as catecholaminergic polymorphic ventricular tachycardia, patients with CRDS are predisposed to sudden death usually in the absence of any electrical abnormalities at rest or during stress electrocardiography. This makes diagnosis incredibly challenging, however, an invasive electrophysiologic test appears to be effective in unmasking the phenotype, called the long-burst, long-pause, short-coupled ventricular extra-stimulus protocol. Optimal therapies for patients with CRDS remain unestablished, although flecainide appears to be a promising candidate drug.

Keywords: Calcium release deficiency syndrome; Catecholaminergic polymorphic ventricular tachycardia; Idiopathic ventricular fibrillation; Inherited arrhythmia; RyR2; Ryanodine receptor; Sudden death.