International CRDS Registry

Population Health Research Institute (PHRI)

Status: Enrolling

Conditions: Calcium Release Deficiency Syndrome

Study type: Observational

Funder types: Other

Identifiers

NCT06508164

16861

Details and patient eligibility

About

Calcium Release Deficiency Syndrome (CRDS) is a newly discovered genetic arrhythmia syndrome that confers a risk of life-threatening arrhythmias secondary to RYR2 loss-of-function. The International CRDS registry has been designed to facilitate large-scale evaluation of CRDS, including its phenotypic spectrum, approaches to risk stratification, and optimal treatment strategies.

Full description

Calcium Release Deficiency Syndrome (CRDS) is a recently discovered inherited arrhythmia syndrome that predisposes to malignant ventricular arrhythmias and sudden cardiac death (SCD). The underlying genetic culprit of CRDS is RYR2, which encodes the cardiac ryanodine receptor. In contrast to Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), which stems from pathogenic RYR2 gain-of-function, CRDS manifests secondary to RyR2 loss-of-function. Enrolment into the CRDS registry requires that the putative disease causing RYR2 variant is confirmed to result in a loss-of-function on in vitro functional analysis. Individuals possessing an RYR2 truncating variant or large copy number variant will be eligible for enrolment into a second registry arm. Patients with a suspected CRDS diagnosis whose RYR2 variant is found not to impact function will be entered into a control arm of the registry.

Given its recent discovery, our understanding of CRDS remains in its infancy. The International CRDS registry has been designed to facilitate evaluation of large numbers of CRDS patients and enable robust insights to hopefully improve management of affected patients and families.

Enrollment: 500 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

CRDS Cohort

Inclusion Criterion:

- Presence of a rare* RYR2 variant that is characterized to be loss-of-function based on in vitro testing#

RYR2 Truncating and Large CNV Cohort

Inclusion Criterion:

- Presence of a rare* RYR2 truncating variant and/or large copy number variant involving the RYR2 gene.

Carriers of a Non-Functional RYR2 variant

Inclusion Criterion:

- Presence of a rare* RYR2 variant that is characterized to be neither loss- nor gain-of-function based on in vitro testing#

*rare defined as gnomAD prevalence < 0.1%

#RYR2 in vitro functional testing will be performed in the laboratory of Dr. Wayne Chen (University of Calgary)

Trial design

500 participants in 3 patient groups

CRDS

Description:

Possesses a rare RYR2 variant characterized to be loss-of-function based on in vitro testing consistent with a CRDS diagnosis

Carrier of an RYR2 truncating variant or large copy number variant

Description:

Possesses a rare RYR2 truncating variant and/or large copy number variant involving the RYR2 gene.

Carrier of a non-functional RYR2 rare variant

Description:

Possesses a rare RYR2 variant that is NOT loss-of-function based on in vitro testing and has a clinical phenotype that was considered compatible with CRDS