Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• European heart journal, 2018-08, Vol.39 (31), p.2879-2887

Ort / Verlag

England: Oxford University Press

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• 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.