Evaluation of a Clinical Diagnostic Test for Calcium Release Deficiency Syndrome: The DIAGNOSE CRDS Study
Population Health Research Institute
Summary
Calcium Release Deficiency Syndrome (CRDS) is a novel inherited arrhythmia syndrome secondary to RyR2 loss-of-function that confers a risk of sudden cardiac death. Diagnosis of CRDS presently requires cellular-based in vitro confirmation that an RyR2 variant causes loss-of-function. We hypothesize that CRDS can be diagnosed clinically through evaluation of the repolarization response to brief tachycardia, mediated by cardiac pacing, and a subsequent pause.
Description
RyR2 loss-of-function variants have recently been established as causative for a new disease termed calcium release deficiency syndrome (CRDS) that confers a risk of malignant ventricular arrhythmias and sudden cardiac death. RyR2 encodes the cardiac ryanodine receptor, the calcium release channel on the sarcoplasmic reticulum that mediates excitation-contraction coupling through calcium-induced calcium-release. In contrast to CRDS, pathogenic RyR2 gain-of-function variants result in an autosomal dominant form of catecholaminergic polymorphic ventricular tachycardia (CPVT). The adrenergic-medi…