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

Alban Elouen Baruteau, Florence Kyndt, Elijah R. Behr, Arja S. Vink, Matthias Lachaud, Anna Joong, Jean Jacques Schott, Minoru Horie, Isabelle Denjoy, Lia Crotti, Wataru Shimizu, Johan M. Bos, Elizabeth A. Stephenson, Leonie Wong, Dominic J. Abrams, Andrew M. Davis, Annika Winbo, Anne M. Dubin, Shubhayan Sanatani, Leonardo LibermanJuan Pablo Kaski, Boris Rudic, Sit Yee Kwok, Claudine Rieubland, Jacob Tfelt-Hansen, George F. Van Hare, Béatrice Guyomarc'h-Delasalle, Nico A. Blom, Yanushi D. Wijeyeratne, Jean Baptiste Gourraud, Hervé Le Marec, Junichi Ozawa, Véronique Fressart, Jean Marc Lupoglazoff, Federica Dagradi, Carla Spazzolini, Takeshi Aiba, David J. Tester, Laura A. Zahavich, Virginie Beauséjour-Ladouceur, Mangesh Jadhav, Jonathan R. Skinner, Sonia Franciosi, Andrew D. Krahn, Mena Abdelsayed, Peter C. Ruben, Tak Cheung Yung, Michael J. Ackerman, Arthur A. Wilde, Peter J. Schwartz, Vincent Probst

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


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.

Original languageEnglish
Pages (from-to)2879-2887
Number of pages9
JournalEuropean heart journal
Issue number31
StatePublished - Aug 1 2018


  • Brugada syndrome
  • Genotype-phenotype correlation
  • Long QT syndrome
  • Progressive cardiac conduction disorders
  • SCN5A
  • Sodium channelopathy


Dive into the research topics of 'SCN5A mutations in 442 neonates and children: Genotype-phenotype correlation and identification of higher-risk subgroups'. Together they form a unique fingerprint.

Cite this