PO-04-090 2 HIT WONDER: AUTOSOMAL RECESSIVE-CPVT WITH CONDUCTION DISEASE

Abstract

Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is a primary arrhythmogenic syndrome with clinical manifestations of syncope and sudden death following exercise or agitation. Present familial cases of autosomal recessive CPVT due to homozygous variants in RYR2 with associated conduction disease. The case was reviewed in detail as below. A 14 year-old girl presented following out of hospital cardiac arrest at a trampoline park. AED strip demonstrated ventricular fibrillation that terminated to sinus rhythm with electrical cardioversion. Workup was notable for a resting ECG with a rate of 52 bpm, a PR of 238 and a right bundle branch block with a QRS duration of 145ms . Exercise stress test resulted in frequent premature ventricular beats and bidirectional couplets. Genetic testing demonstrated homozygosity of a novel VUS in RYR2 (c.9392A>C (p.Tyr3131Ser)). Analysis by REVEL demonstrated a score of (0.763), predicting pathogenicity. Parents were found to be heterozygous asymptomatic carriers of the same variant and one sibling was homozygous for the variant. This sibling had a prolonged PR interval and intraventricular conduction delay and was phenotypically positive during exercise stress test. Two siblings who were heterozygous for the variant had normal ECG and exercise stress tests. The proband was started on nadalol and flecainide and a dual chamber ICD was placed for secondary prevention and significant sinus bradycardia prior to initiation of antiarrhythmics. On follow up EST the patient was noted to have acute onset high grade AV block during exercise resulting in initiation of ventricular pacing as well as runs of atrial tachycardia. Baseline ECG did not demonstrate QRS widening and flecainide level was within limits. The affected sibling was started on nadolol. We report two cases of patients homozygous for a VUS in RYR2 manifesting phenotypically as CPVT with associated conduction disease. Further study of this distinct phenotype of CPVT is warranted.