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Comment
. 2023 May 19;25(5):euad079.
doi: 10.1093/europace/euad079.

Genetic testing in children with Brugada syndrome: results from a large prospective registry

Luigi Pannone  1 , Antonio Bisignani  1 , Randy Osei  2 , Anaïs Gauthey  1 , Antonio Sorgente  1 , Pasquale Vergara  1 , Cinzia Monaco  1 , Domenico Giovanni Della Rocca  1 , Alvise Del Monte  1 , Antanas Strazdas  1 , Joerelle Mojica  1 , Maysam Al Housari  1 , Vincenzo Miraglia  1 , Sahar Mouram  1 , Gaetano Paparella  1 , Robbert Ramak  1 , Ingrid Overeinder  1 , Gezim Bala  1 , Alexandre Almorad  1 , Erwin Ströker  1 , Gudrun Pappaert  1 , Juan Sieira  1 , Thomy de Ravel  2 , Mark La Meir  3 , Pedro Brugada  1 , Gian Battista Chierchia  1 , Sonia Van Dooren  2   4 , Carlo de Asmundis  1
Affiliations
Comment

Genetic testing in children with Brugada syndrome: results from a large prospective registry

Luigi Pannone et al. Europace. .

Abstract

Aims: A pathogenic/likely pathogenic (P/LP) variant in SCN5A is found in 20-25% of patients with Brugada syndrome (BrS). However, the diagnostic yield and prognosis of gene panel testing in paediatric BrS is unclear. The aim of this study is to define the diagnostic yield and outcomes of SCN5A gene testing with ACMG variant classification in paediatric BrS patients compared with adults.

Methods and results: All consecutive patients diagnosed with BrS, between 1992 and 2022, were prospectively enrolled in the UZ Brussel BrS registry. Inclusion criteria were: (i) BrS diagnosis; (ii) genetic analysis performed with a large gene panel; and (iii) classification of gene variants following ACMG guidelines. Paediatric patients were defined as ≤16 years of age. The primary endpoint was ventricular arrhythmias (VAs). A total of 500 BrS patients were included, with 63 paediatric patients and 437 adult patients. Among children with BrS, 29 patients (46%) had a P/LP variant (P+) in SCN5A and no variants were found in 34 (54%) patients (P-). After a mean follow-up of 125.9 months, 8 children (12.7%) experienced a VA, treated with implanted cardioverter defibrillator shock. At survival analysis, P- paediatric patients had higher VA-free survival during the follow-up, compared with P+ paediatric patients. P+ status was an independent predictor of VA. There was no difference in VA-free survival between paediatric and adult BrS patients for both P- and P+.

Conclusion: In a large BrS cohort, the diagnostic yield for P/LP variants in the paediatric population is 46%. P+ children with BrS have a worse arrhythmic prognosis.

Keywords: Brugada syndrome; Genetics; SCN5A; Sudden cardiac death; Ventricular arrhythmias.

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Conflict of interest statement

Conflict of interest: A.B. is a consultant for Biotronik. A.S. received research grants from Daiichi-Sankyo and Bayer; he has received speaker fees from Menarini and Bayer. V.M. received an educational grant from the Foundation ‘Enrico and Enrica Sovena’. M.L.M. is consultant for Atricure. P.B. received compensation for teaching purposes from Biotronik. G.B.C. received compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, Boston Scientific, and Acutus Medical. C.d.A. receives research grants on behalf of the centre from Biotronik, Medtronic, Abbott, LivaNova, Boston Scientific, AtriCure, Philips, and Acutus; C.d.A. received compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, LivaNova, Boston Scientific, Atricure, Acutus Medical Daiichi Sankyo. The remaining authors have nothing to disclose.

Figures

Graphical Abstract
Graphical Abstract
Figure 1
Figure 1
Kaplan–Meier curves of survival free from ventricular arrhythmia occurrence by P/LP variant carrier status in a paediatric Brugada syndrome population (≤16 years). Kaplan–Meier curve of survival free from VA occurrence by P/LP variant; patients without any P/LP variants (P−) (blue, upper curve) had higher VA-free survival during the follow-up, compared with those with a P/LP variant (P+) patients (red, lower curve) (94.1 vs. 79.3%, Log-rank P = 0.03). P/LP, pathogenic/likely pathogenic; VA, ventricular arrhythmia.
Figure 2
Figure 2
Kaplan–Meier curves of survival free from ventricular arrhythmia occurrence in Brugada syndrome by age group: paediatric cohort (≤16 years) vs. adult cohort (>16 years). Kaplan–Meier curve of survival free from ventricular arrhythmia (VA) occurrence. There was no difference in VA-free survival between paediatric Brugada syndrome (BrS) patients (red, lower curve) and adult BrS patients (blue, upper curve) (87.3 vs. 90.8%, Log-rank P = 0.47).
Figure 3
Figure 3
Kaplan–Meier curves of survival free from ventricular arrhythmia occurrence by pathogenic/likely pathogenic (P/LP) variant carrier status and paediatric (≤16 years) vs. adult (>16 years) Brugada syndrome. Kaplan–Meier curve of survival free from ventricular arrhythmia (VA) occurrence. There was no difference in VA-free survival between P− paediatric Brugada syndrome (BrS) patients (green curve, upper) and P− adult BrS patients (blue curve, middle upper) (94.1 vs. 92.5%, pairwise Log-rank P = 0.55). There was no difference in VA-free survival in P+ paediatric BrS patients (purple curve, lower) and P+ adult BrS patients (red curve, middle lower) (79.3 vs. 82.7%, pairwise Log-rank P = 0.45).
See this image and copyright information in PMC

Comment on

  • Characterization and Management of Arrhythmic Events in Young Patients With Brugada Syndrome.
    Michowitz Y, Milman A, Andorin A, Sarquella-Brugada G, Gonzalez Corcia MC, Gourraud JB, Conte G, Sacher F, Juang JJM, Kim SH, Leshem E, Mabo P, Postema PG, Hochstadt A, Wijeyeratne YD, Denjoy I, Giustetto C, Mizusawa Y, Huang Z, Jespersen CH, Maeda S, Takahashi Y, Kamakura T, Aiba T, Arbelo E, Mazzanti A, Allocca G, Brugada R, Casado-Arroyo R, Champagne J, Priori SG, Veltmann C, Delise P, Corrado D, Brugada J, Kusano KF, Hirao K, Calo L, Takagi M, Tfelt-Hansen J, Yan GX, Gaita F, Leenhardt A, Behr ER, Wilde AAM, Nam GB, Brugada P, Probst V, Belhassen B. Michowitz Y, et al. J Am Coll Cardiol. 2019 Apr 16;73(14):1756-1765. doi: 10.1016/j.jacc.2019.01.048. J Am Coll Cardiol. 2019. PMID: 30975291

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