International CRDS Registry
Purpose
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.
Condition
- Calcium Release Deficiency Syndrome
Eligibility
- Eligible Ages
- All ages
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
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)
Study Design
- Phase
- Study Type
- Observational [Patient Registry]
- Observational Model
- Cohort
- Time Perspective
- Prospective
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
| CRDS | 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 | Possesses a rare RYR2 truncating variant and/or large copy number variant involving the RYR2 gene. | |
| Carrier of a non-functional RYR2 rare variant | 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 |
Recruiting Locations
San Francisco 5391959, California 5332921 94143
Rochester 5043473, Minnesota 5037779 55905
Durham 4464368, North Carolina 4482348 27710
More Details
- Status
- Recruiting
- Sponsor
- Population Health Research Institute
Detailed 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.