Population Health Research Institute
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.
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…
Cohort 1: Calcium Release Deficiency Syndrome (CRDS) Cases Inclusion criteria: • Presence of an RyR2 variant confirmed to be loss-of-function on in vitro testing Exclusion criteria: • Unable to provide informed consent Cohort 2: Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) Cases Inclusion criteria: * Satisfy a clinical phenotype consistent with the Expert Consensus Statement * Presence of a confirmed or presumed pathogenic gain-of-function RyR2 variant OR homozygous or compound heterozygous for likely pathogenic/pathogenic CASQ2 variants Exclusion criteria: * Unable to…
1. Ventricular 10 beat burst at 500ms (120bpm) 2. Ventricular 10 beat burst at 400ms (150bpm) 3. Atrial 10 beat burst at 500ms (120bpm) 4. Atrial 10 beat burst at 400ms (150bpm).