Familial evaluation in catecholaminergic polymorphic ventricular tachycardia: disease penetrance and expression in cardiac ryanodine receptor mutation-carrying relatives.

Details

Serval ID
serval:BIB_5312E787FD56
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Familial evaluation in catecholaminergic polymorphic ventricular tachycardia: disease penetrance and expression in cardiac ryanodine receptor mutation-carrying relatives.
Journal
Circulation. Arrhythmia and Electrophysiology
Author(s)
van der Werf C., Nederend I., Hofman N., van Geloven N., Ebink C., Frohn-Mulder I.M., Alings A.M., Bosker H.A., Bracke F.A., van den Heuvel F., Waalewijn R.A., Bikker H., van Tintelen J.P., Bhuiyan Z.A., van den Berg M.P., Wilde A.A.
ISSN
1941-3084 (Electronic)
ISSN-L
1941-3084
Publication state
Published
Issued date
2012
Peer-reviewed
Oui
Volume
5
Number
4
Pages
748-756
Language
english
Notes
Publication types: Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
Abstract
BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome associated with mutations in the cardiac ryanodine receptor gene (Ryr2) in the majority of patients. Previous studies of CPVT patients mainly involved probands, so current insight into disease penetrance, expression, genotype-phenotype correlations, and arrhythmic event rates in relatives carrying the Ryr2 mutation is limited.
METHODS AND RESULTS: One-hundred sixteen relatives carrying the Ryr2 mutation from 15 families who were identified by cascade screening of the Ryr2 mutation causing CPVT in the proband were clinically characterized, including 61 relatives from 1 family. Fifty-four of 108 antiarrhythmic drug-free relatives (50%) had a CPVT phenotype at the first cardiological examination, including 27 (25%) with nonsustained ventricular tachycardia. Relatives carrying a Ryr2 mutation in the C-terminal channel-forming domain showed an increased odds of nonsustained ventricular tachycardia (odds ratio, 4.1; 95% CI, 1.5-11.5; P=0.007, compared with N-terminal domain) compared with N-terminal domain. Sinus bradycardia was observed in 19% of relatives, whereas other supraventricular dysrhythmias were present in 16%. Ninety-eight (most actively treated) relatives (84%) were followed up for a median of 4.7 years (range, 0.3-19.0 years). During follow-up, 2 asymptomatic relatives experienced exercise-induced syncope. One relative was not being treated, whereas the other was noncompliant. None of the 116 relatives died of CPVT during a 6.7-year follow-up (range, 1.4-20.9 years).
CONCLUSIONS: Relatives carrying an Ryr2 mutation show a marked phenotypic diversity. The vast majority do not have signs of supraventricular disease manifestations. Mutation location may be associated with severity of the phenotype. The arrhythmic event rate during follow-up was low.
Keywords
Adolescent, Adult, Aged, Child, Child, Preschool, DNA Mutational Analysis, Electrocardiography, Female, Genetic Association Studies, Genetic Predisposition to Disease, Heart Conduction System/physiopathology, Heredity, Humans, Kaplan-Meier Estimate, Logistic Models, Male, Middle Aged, Multivariate Analysis, Mutation, Netherlands, Odds Ratio, Pedigree, Penetrance, Phenotype, Prognosis, Risk Assessment, Risk Factors, Ryanodine Receptor Calcium Release Channel/genetics, Severity of Illness Index, Tachycardia, Ventricular/diagnosis, Tachycardia, Ventricular/genetics, Time Factors, Young Adult
Pubmed
Web of science
Open Access
Yes
Create date
14/02/2013 19:01
Last modification date
20/08/2019 15:08
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