Familial Evaluation in Catecholaminergic Polymorphic Ventricular Tachycardia Disease Penetrance and Expression in Cardiac Ryanodine Receptor Mutation-Carrying Relatives

Autor: Corné Ebink, Ineke Nederend, A. Marco Alings, Hennie Bikker, Nynke Hofman, J. Peter van Tintelen, Frank A.L.E. Bracke, Christian van der Werf, Ingrid M.E. Frohn-Mulder, Nan van Geloven, Reinier A. Waalewijn, Hans A. Bosker, Zahurul A. Bhuiyan, Arthur A.M. Wilde, Maarten P. van den Berg, Freek van den Heuvel
Přispěvatelé: Ethical, Legal, Social Issues in Genetics (ELSI), Cardiovascular Centre (CVC), Cardiology, Human Genetics, Clinical Research Unit, ACS - Amsterdam Cardiovascular Sciences, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Other Research, Other departments
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Proband
Male
MECHANISM
Heredity
Time Factors
Sinus bradycardia
FEATURES
DNA Mutational Analysis
Penetrance
Kaplan-Meier Estimate
Ventricular tachycardia
Ryanodine receptor 2
Severity of Illness Index
Electrocardiography
Risk Factors
Odds Ratio
genetics
Child
death
sudden
Netherlands
catecholaminergic polymorphic ventricular tachycardia
ion channels
Middle Aged
Prognosis
CARRIERS
Pedigree
Phenotype
Child
Preschool
Cardiology
cardiovascular system
Female
medicine.symptom
Cardiology and Cardiovascular Medicine
tachyarrhythmias
Adult
medicine.medical_specialty
Adolescent
Catecholaminergic polymorphic ventricular tachycardia
Asymptomatic
Sudden death
Risk Assessment
Young Adult
SUDDEN-DEATH
Heart Conduction System
Physiology (medical)
Internal medicine
death
medicine
RELEASE CHANNEL
Humans
Genetic Predisposition to Disease
Genetic Association Studies
Aged
sudden
SPECTRUM
business.industry
Ryanodine Receptor Calcium Release Channel
medicine.disease
GENE
DYSFUNCTION
Endocrinology
Logistic Models
ARRHYTHMIA SYNDROMES
Multivariate Analysis
Mutation
Tachycardia
Ventricular
business
FOLLOW-UP
Zdroj: Circulation. Arrhythmia and Electrophysiology, 5(4), 748-756. LIPPINCOTT WILLIAMS & WILKINS
Circulation. Arrhythmia and electrophysiology, 5(4), 748-756. Lippincott Williams and Wilkins
ISSN: 1941-3084
1941-3149
Popis: 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.
Databáze: OpenAIRE
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