Key result
Family screening identifies RyR2 mutations, with ~65% of carriers showing effort-induced arrhythmias.
Why the study?
Although RyR2 mutations are associated with stress-induced polymorphic ventricular arrhythmia, syncope, and sudden death, the role of genetic screening for RyR2 mutations in affected families needed to be established.
What is the role of genetic screening for RyR2 mutations in identifying carriers among families with effort-induced polymorphic ventricular arrhythmia, syncope, and juvenile sudden death?
Cohort (n=81)
What is the role of genetic screening for RyR2 mutations in identifying carriers among families with effort-induced polymorphic ventricular arrhythmia, syncope, and juvenile sudden death?
Genetic screening is essential for early diagnosis of asymptomatic RyR2 mutation carriers and prevention of sudden death, as over one-third of carriers lack symptoms or inducible arrhythmias on exercise stress testing and EP study.
Answers are grounded in this paper and cite their sources.
May support targeted RYR2 screening in select families; leaves open prospective validation before clinical adoption.
Objectives We sought to establish the role of genetic screening for ryanodine receptor type 2 (RyR2) gene mutations in families with effort-induced polymorphic ventricular arrhythmia (PVA), syncope and juvenile sudden death. Background The RyR2 mutations have been associated with PVA, syncope and sudden death in response to physical or emotional stress. Methods We studied 81 subjects (39 males and 42 females; mean age 31 +/- 20 years) belonging to eight families with pathogenic RyR2 mutations. All subjects underwent screening for RyR2 mutations, electrocardiography (ECG), 24-h Holter monitoring, signal-averaged electrocardiography (SAECG), two-dimensional echocardiography and exercise stress testing. Electrophysiologic (EP) study was performed in nine patients. Results Six different RyR2 mutations were found in eight families. Forty-three family members carried the gene mutation. Of these, 28 (65%) showed effort-induced arrhythmic symptoms or signs and one died suddenly during follow-up. Family history revealed 19 juvenile cases of sudden death during effort or emotion. In two families sharing the same mutation, no subject presented with PVA during the stress test; thus, sudden death and syncope were the only clinical manifestations. The 12-lead ECG was normal in all but two subjects, whereas five patients showed positive late potentials on the SAECG. In 17 (39.5%) of 43 subjects, the two-dimensional echocardiogram revealed localized kinetic abnormalities and mild structural alterations of the right ventricle. The EP study was not able to induce PVA. Conclusions The absence of symptoms and PVA on the stress test in more than one-third of carriers of RyR2 mutations, as well as the lack of PVA inducibility by the EP study, underlies the importance of genetic screening for the early diagnosis of asymptomatic carriers and prevention of sudden death.
No takes yet. Share an insight, caveat, or question.
Bauce et al. (2002) conducted a cohort in Families with effort-induced polymorphic ventricular arrhythmia, syncope, and juvenile sudden death (n=81). Genetic screening for ryanodine receptor type 2 (RyR2) mutations and clinical evaluation was evaluated on Effort-induced arrhythmic symptoms or signs in RyR2 mutation carriers. Genetic screening identified 43 RyR2 mutation carriers among 81 family members, of whom 65% had effort-induced arrhythmic signs/symptoms and 35% were asymptomatic on stress testing.
Synapse has enriched 10 related papers. Consider them for comparative context: