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  • SCN5A mutations in 442 neonates and children: genotype-phenotype correlation and identification of higher-risk subgroups EUROPEAN HEART JOURNAL Baruteau, A., Kyndt, F., Behr, E. R., Vink, A. S., Lachaud, M., Joong, A., Schott, J., Horie, M., Denjoy, I., Crotti, L., Shimizu, W., Bos, J. M., Stephenson, E. A., LeonieWong, Abrams, D. J., Davis, A. M., Winbo, A., Dubin, A. M., Sanatani, S., Liberman, L., Kaski, J., Rudic, B., Kwok, S., Rieubland, C., Tfelt-Hansen, J., Van Hare, G. F., Guyomarc'h-Delasalle, B., Blom, N. A., Wijeyeratne, Y. D., Gourraud, J., Le Marec, H., Ozawa, J., Fressart, V., Lupoglazoff, J., Dagradi, F., Spazzolini, C., Aiba, T., Tester, D. J., Zahavich, L. A., Beausejour-Ladouceur, V., Jadhav, M., Skinner, J. R., Franciosi, S., Krahn, A. D., Abdelsayed, M., Ruben, P. C., Yung, T., Ackerman, M. J., Wilde, A. A., Schwartz, P. J., Probst, V. 2018; 39 (31): 2879-+


    To clarify the clinical characteristics and outcomes of children with SCN5A-mediated disease and to improve their risk stratification.A multicentre, international, retrospective cohort study was conducted in 25 tertiary hospitals in 13 countries between 1990 and 2015. All patients ≤16 years of age diagnosed with a genetically confirmed SCN5A mutation were included in the analysis. There was no restriction made based on their clinical diagnosis. A total of 442 children {55.7% boys, 40.3% probands, median age: 8.0 [interquartile range (IQR) 9.5] years} from 350 families were included; 67.9% were asymptomatic at diagnosis. Four main phenotypes were identified: isolated progressive cardiac conduction disorders (25.6%), overlap phenotype (15.6%), isolated long QT syndrome type 3 (10.6%), and isolated Brugada syndrome type 1 (1.8%); 44.3% had a negative electrocardiogram phenotype. During a median follow-up of 5.9 (IQR 5.9) years, 272 cardiac events (CEs) occurred in 139 (31.5%) patients. Patients whose mutation localized in the C-terminus had a lower risk. Compound genotype, both gain- and loss-of-function SCN5A mutation, age ≤1 year at diagnosis in probands and age ≤1 year at diagnosis in non-probands were independent predictors of CE.In this large paediatric cohort of SCN5A mutation-positive subjects, cardiac conduction disorders were the most prevalent phenotype; CEs occurred in about one-third of genotype-positive children, and several independent risk factors were identified, including age ≤1 year at diagnosis, compound mutation, and mutation with both gain- and loss-of-function.

    View details for PubMedID 30059973