SCN5A mutations in 442 neonates and children: genotype–phenotype correlation and identification of higher-risk subgroups

Abstract Aims To clarify the clinical characteristics and outcomes of children with SCN5A-mediated disease and to improve their risk stratification. Methods and results A multicentre, international, retrospective cohort study was conducted in 25 tertiary hospitals in 13 countries between 1990 and 20...

Full description

Saved in:

Bibliographic Details
Published in:	European heart journal Vol. 39; no. 31; pp. 2879 - 2887
Main Authors:	Baruteau, Alban-Elouen, Kyndt, Florence, Behr, Elijah R, Vink, Arja S, Lachaud, Matthias, Joong, Anna, Schott, Jean-Jacques, Horie, Minoru, Denjoy, Isabelle, Crotti, Lia, Shimizu, Wataru, Bos, Johan M, Stephenson, Elizabeth A, Wong, Leonie, Abrams, Dominic J, Davis, Andrew M, Winbo, Annika, Dubin, Anne M, Sanatani, Shubhayan, Liberman, Leonardo, Kaski, Juan Pablo, Rudic, Boris, Kwok, Sit Yee, Rieubland, Claudine, Tfelt-Hansen, Jacob, Van Hare, George F, Guyomarc’h-Delasalle, Béatrice, Blom, Nico A, Wijeyeratne, Yanushi D, Gourraud, Jean-Baptiste, Le Marec, Hervé, Ozawa, Junichi, Fressart, Véronique, Lupoglazoff, Jean-Marc, Dagradi, Federica, Spazzolini, Carla, Aiba, Takeshi, Tester, David J, Zahavich, Laura A, Beauséjour-Ladouceur, Virginie, Jadhav, Mangesh, Skinner, Jonathan R, Franciosi, Sonia, Krahn, Andrew D, Abdelsayed, Mena, Ruben, Peter C, Yung, Tak-Cheung, Ackerman, Michael J, Wilde, Arthur A, Schwartz, Peter J, Probst, Vincent
Format:	Journal Article
Language:	English
Published:	England Oxford University Press 14-08-2018 Oxford University Press (OUP)
Subjects:	Life Sciences Long QT syndrome Progressive cardiac conduction disorders Genotype–phenotype correlation SCN5A Brugada syndrome Sodium channelopathy
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Abstract Aims To clarify the clinical characteristics and outcomes of children with SCN5A-mediated disease and to improve their risk stratification. Methods and results 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. Conclusion 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0195-668X 1522-9645
DOI:	10.1093/eurheartj/ehy412