A Novel Variant in RYR2 Causes Autosomal Recessive Catecholamineric Polymorphic Ventricular Tachycardia , Presenting with Cardiac Arrest & Ventricular Fibrillation

Background:
Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is a rare cardiac channelopathy characterized by exercise or emotion induced bidirectional ventricular tachycardia. The autosomal dominant type of the disease (CPVT1) is caused by mutations in the Ryanodine receptor (RYR2).

Objective:
We describe a family with autosomal recessive segregation of CPVT1 caused by a novel RYR2 mutation.

Methods:
ECG, stress test, echocardiography, genetic testing.

Results:
A 19 years old male from Jerusalem presented with cardiac arrest (CA) during physical stress. While visiting him in the intensive care unit, his 13 years old sister underwent CA as well. Workup revealed asymptomatic parents and siblings, of which one had multifocal premature ventricular contractions during stress test. G3118R missense mutation in RYR2 was found with recessive segregation: The affected members are homozygous for the mutation whereas the non-affected parents and siblings are heterozygous (figure). This variant was not reported in ExAC database. It is located in the cytosolic component of the RYR2 outside areas with frequent cluster mutations. The affected members underwent ICD implantation and have been receiving Metoprolol. During nine years of follow up the female had an episode of multiple VF and shocks (figure). Metoprolol dose was increased. No further episodes occurred.

Conclusion:
A report of autosomal recessive CPVT1 caused by RYR2 mutation. It suggests different or a less severe mechanism for RYR2 function disruption.