Clinical Spectrum of Arrhythmogenic Entities in Spanish Children Carrying Deleterious SCN5A Variants
Por:
Martínez-Barrios E, Cruzalegui JC, Hidalgo-Sanuy M, Greco A, César-Díaz S, Chipa F, Nuria Díez Escuté, Patricia Cerralbo Martín, Zschaeck-Luzardo I, Merchán F, Balsells S, Brugada-Terradellas J, Campuzano O and Sarquella-Brugada G
Publicada:
15 ene 2026
Ahead of Print:
15 ene 2026
Resumen:
Deleterious variants in SCN5A lead to a wide clinical spectrum that
includes pathologies characterized by life-threatening cardiac events
(CEs). In the pediatric population, early identification, management,
and risk stratification of these pathologies are the main current
challenges. This study analyzed a Spanish pediatric cohort (<= 18 years)
carrying rare SCN5A variants to explore genotype-phenotype correlations.
A retrospective descriptive cohort study, including clinical,
demographic, and genetic data of probands and their relatives, was
conducted. Out of 100 children studied, 69 had definitively deleterious
SCN5A variants (26 females, 38%; median age: 3 years, IQR 1-12). The
main diagnoses were isolated Brugada syndrome (BrS) (31; 45%); isolated
long QT syndrome type 3 (LQT3) (5; 7%); isolated progressive cardiac
conduction disease (PCCD) (1; 2%); isolated familial atrial fibrillation
(1; 2%); overlapping phenotypes (7; 10%) including: BrS-PCCD (2; 2.8%);
BrS-LQT3 (1; 1.4%); premature ventricular contraction-dilated
cardiomyopathy (1; 1.4%); BrS-LQT3-PCCD (1; 1.4%); BrS-PCCD-sick sinus
syndrome (SSS) (1; 1.4%) and BrS-PCCD-SSS-familial atrial fibrillation
(1; 1.4%). Of them, 13 (19%) patients presented with CEs (cardiogenic
syncope, ventricular tachycardia/fibrillation, sudden cardiac
arrest/death, and appropriate implantable cardio defibrillator shock).
These findings underscore the utility of genetic testing for early
diagnosis, risk stratification, and personalized management, enhancing
preventive strategies for CE prevention in pediatrics.
Filiaciones:
Martínez-Barrios E:
Pediatric Arrhythmias, Genetic Cardiology and Sudden Death, Institut de Recerca Sant Joan de Déu (IRSJD), Santa Rosa 39-57, Esplugues de Llobregat, 08950 Barcelona, Spain
Arrhythmia, Inherited Cardiac Diseases and Sudden Death Unit, Department of Cardiology, Hospital Sant Joan de Déu Barcelona, Passeig Sant Joan de Déu 2, Esplugues de Llobregat, 08950 Barcelona, Spain
European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), 1105 AZ Amsterdam, The Netherlands
Cruzalegui JC:
Pediatric Arrhythmias, Genetic Cardiology and Sudden Death, Institut de Recerca Sant Joan de Déu (IRSJD), Santa Rosa 39-57, Esplugues de Llobregat, 08950 Barcelona, Spain
Arrhythmia, Inherited Cardiac Diseases and Sudden Death Unit, Department of Cardiology, Hospital Sant Joan de Déu Barcelona, Passeig Sant Joan de Déu 2, Esplugues de Llobregat, 08950 Barcelona, Spain
European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), 1105 AZ Amsterdam, The Netherlands
Hidalgo-Sanuy M:
Pediatric Arrhythmias, Genetic Cardiology and Sudden Death, Institut de Recerca Sant Joan de Déu (IRSJD), Santa Rosa 39-57, Esplugues de Llobregat, 08950 Barcelona, Spain
Greco A:
Pediatric Arrhythmias, Genetic Cardiology and Sudden Death, Institut de Recerca Sant Joan de Déu (IRSJD), Santa Rosa 39-57, Esplugues de Llobregat, 08950 Barcelona, Spain
Arrhythmia, Inherited Cardiac Diseases and Sudden Death Unit, Department of Cardiology, Hospital Sant Joan de Déu Barcelona, Passeig Sant Joan de Déu 2, Esplugues de Llobregat, 08950 Barcelona, Spain
European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), 1105 AZ Amsterdam, The Netherlands
César-Díaz S:
Pediatric Arrhythmias, Genetic Cardiology and Sudden Death, Institut de Recerca Sant Joan de Déu (IRSJD), Santa Rosa 39-57, Esplugues de Llobregat, 08950 Barcelona, Spain
Arrhythmia, Inherited Cardiac Diseases and Sudden Death Unit, Department of Cardiology, Hospital Sant Joan de Déu Barcelona, Passeig Sant Joan de Déu 2, Esplugues de Llobregat, 08950 Barcelona, Spain
European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), 1105 AZ Amsterdam, The Netherlands
:
Pediatric Arrhythmias, Genetic Cardiology and Sudden Death, Institut de Recerca Sant Joan de Déu (IRSJD), Santa Rosa 39-57, Esplugues de Llobregat, 08950 Barcelona, Spain
Arrhythmia, Inherited Cardiac Diseases and Sudden Death Unit, Department of Cardiology, Hospital Sant Joan de Déu Barcelona, Passeig Sant Joan de Déu 2, Esplugues de Llobregat, 08950 Barcelona, Spain
European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), 1105 AZ Amsterdam, The Netherlands
Nuria Díez Escuté:
Pediatric Arrhythmias, Genetic Cardiology and Sudden Death, Institut de Recerca Sant Joan de Déu (IRSJD), Santa Rosa 39-57, Esplugues de Llobregat, 08950 Barcelona, Spain
Arrhythmia, Inherited Cardiac Diseases and Sudden Death Unit, Department of Cardiology, Hospital Sant Joan de Déu Barcelona, Passeig Sant Joan de Déu 2, Esplugues de Llobregat, 08950 Barcelona, Spain
European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), 1105 AZ Amsterdam, The Netherlands
Patricia Cerralbo Martín:
Pediatric Arrhythmias, Genetic Cardiology and Sudden Death, Institut de Recerca Sant Joan de Déu (IRSJD), Santa Rosa 39-57, Esplugues de Llobregat, 08950 Barcelona, Spain
Arrhythmia, Inherited Cardiac Diseases and Sudden Death Unit, Department of Cardiology, Hospital Sant Joan de Déu Barcelona, Passeig Sant Joan de Déu 2, Esplugues de Llobregat, 08950 Barcelona, Spain
European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), 1105 AZ Amsterdam, The Netherlands
Zschaeck-Luzardo I:
Pediatric Arrhythmias, Genetic Cardiology and Sudden Death, Institut de Recerca Sant Joan de Déu (IRSJD), Santa Rosa 39-57, Esplugues de Llobregat, 08950 Barcelona, Spain
European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), 1105 AZ Amsterdam, The Netherlands
:
Pediatric Arrhythmias, Genetic Cardiology and Sudden Death, Institut de Recerca Sant Joan de Déu (IRSJD), Santa Rosa 39-57, Esplugues de Llobregat, 08950 Barcelona, Spain
Arrhythmia, Inherited Cardiac Diseases and Sudden Death Unit, Department of Cardiology, Hospital Sant Joan de Déu Barcelona, Passeig Sant Joan de Déu 2, Esplugues de Llobregat, 08950 Barcelona, Spain
European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), 1105 AZ Amsterdam, The Netherlands
Balsells S:
Statistical Advising Service, Fundació de Recerca Sant Joan de Déu, Santa Rosa 39-57, 08950 Esplugues de Llobregat, Spain
Brugada-Terradellas J:
Centro de Investigación Biomédica en Red, Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain
Arrhythmias Unit, Hospital Clinic, University of Barcelona, 08036 Barcelona, Spain
:
Centro de Investigación Biomédica en Red, Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain
Medical Science Department, School of Medicine, Universitat de Girona, 17003 Girona, Spain
Institut d'Investigació Biomèdica de Girona (IDIBGI-CERCA), Parc Hospitalari Martí i Julià, Edifici M2, 17190 Salt, Spain
Sarquella-Brugada G:
Pediatric Arrhythmias, Genetic Cardiology and Sudden Death, Institut de Recerca Sant Joan de Déu (IRSJD), Santa Rosa 39-57, Esplugues de Llobregat, 08950 Barcelona, Spain
Arrhythmia, Inherited Cardiac Diseases and Sudden Death Unit, Department of Cardiology, Hospital Sant Joan de Déu Barcelona, Passeig Sant Joan de Déu 2, Esplugues de Llobregat, 08950 Barcelona, Spain
European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), 1105 AZ Amsterdam, The Netherlands
Medical Science Department, School of Medicine, Universitat de Girona, 17003 Girona, Spain
Departament de Pediatria, Facultat de Medicina i Ciències Mèdiques, Universitat de Barcelona, 08007 Barcelona, Spain
Green Accepted, Green Submitted, gold
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