Genetics can contribute to the prognosis of Brugada syndrome: a pilot model for risk stratification

Abstract

Brugada syndrome is an inherited arrhythmogenic disorder leading to sudden death predominantly in the 3-4 decade. To date the only reliable treatment is the implantation of a cardioverter defibrillator; however, better criteria for risk stratification are needed, especially for asymptomatic subjects. Brugada syndrome genetic bases have been only partially understood, accounting for o30% of patients, and have been poorly correlated with prognosis, preventing inclusion of genetic data in current guidelines. We designed an observational study to identify genetic markers for risk stratification of Brugada patients by exploratory statistical analysis. The presence of genetic variants, identified by SCN5A gene analysis and genotyping of 73 candidate polymorphisms, was correlated with the occurrence of major arrhythmic events in a cohort of 92 Brugada patients by allelic association and survival analysis. In all, 18 mutations were identified in the SCN5A gene, including 5 novel, and statistical analysis indicated that mutation carriers had a significantly increased risk of major arrhythmic events (P ¼ 0.024). In addition, we established association of five polymorphisms with major arrhythmic events occurrence and consequently elaborated a pilot risk stratification algorithm by calculating a weighted genetic risk score, including the associated polymorphisms and the presence of SCN5A mutation as function of their odds ratio. This study correlates for the first time the presence of genetic variants with increased arrhythmic risk in Brugada patients, representing a first step towards the design of a new risk stratification model.

Impact of clinical and genetic findings on the management of young patients with Brugada syndrome

“…By contrast, none of the 17 genotype-negative patients, suffered a LTA event. Thus, in our cohort the presence of a SCN5A mutation may be necessary, but is insufficient on its own for the development of LTA 23,24 . These results should, however, be treated cautiously due to the low number of patients and the high prevalence of SCN5A mutations.…”

Genetic Insurance Discrimination in Sudden Arrhythmia Death Syndromes

“…37 Classifying all individuals with LQTS as high-risk individuals is unsubstantiated; risk stratification exists for LQTS and other channelopathies. [38][39][40][41][42][43][44][45] It is unlikely that these are known or applied by the insurers. Finally, being a mutation carrier does not necessarily indicate risk for SADS because diagnosed cases are not always confirmed by genetic testing.…”

Brugada syndrome and cardiac sodium channelopathy overlap syndromes: different faces of SCN5A mutations

“…Шесть (43%) пробандов с известными мута-циями Q1118X [16][17][18] и G1743R [18][19][20][21], а так-же с новыми миссенс-мутацией F919S, нонсенс-мутацией E1574Х и мутациями сплайсинга IVS16DS-5A>G и IVS24AS+1G>A демонстриро-вали изолированный фенотип синдрома Бруга-да. У них отмечалось синкопальное течение за-болевания с личным (Q1118X, IVS24AS+1G>A, G1743R) и семейным (за исключением F919S, Q1118X и E1574Х) анамнезом ВСС, спонтанным Бругада-паттерном I типа на ЭКГ, в связи с чем необходимость в фармакологических пробах от-сутствовала.…”