Calcium Release Deficiency Syndrome
Conditions
Brief summary
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.
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.
Interventions
None listed
Sponsors
Population Health Research Institute
Canadian Institutes of Health Research (CIHR)
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Malignant Ventricular Arrhythmia | 5 years | Composite of malignant syncope, ICD shock, cardiac arrest, and sudden cardiac death |
Countries
Australia, Belgium, Canada, Denmark, France, Israel, United Kingdom, United States
Contacts
CONTACTJason D Roberts, MD MAS
STUDY_CHAIRThomas M Roston, MD, PhD
University of British Columbia
PRINCIPAL_INVESTIGATORJason D Roberts, MD MAS
McMaster University
PRINCIPAL_INVESTIGATORSR Wayne Chen, PhD
University of Calgary
Outcome results
None listed