Hostname: page-component-745bb68f8f-kw2vx Total loading time: 0 Render date: 2025-01-24T23:53:08.989Z Has data issue: false hasContentIssue false
  • English
  • Français

Brugada syndrome in the paediatric population: a comprehensive approach to clinical manifestations, diagnosis, and management

Published online by Cambridge University Press:  06 May 2016

M. Cecilia Gonzalez Corcia ,
Carlo de Asmundis ,
Gian-Battista Chierchia  and
Pedro Brugada
M. Cecilia Gonzalez Corcia*
Affiliation:
Pediatric Cardiology Department, Cliniques Universitaires St Luc, Brussels, Belgium
Carlo de Asmundis
Affiliation:
Heart Rhythm Management Centre, UZ Brussel-VUB, Brussels, Belgium
Gian-Battista Chierchia
Affiliation:
Heart Rhythm Management Centre, UZ Brussel-VUB, Brussels, Belgium
Pedro Brugada
Affiliation:
Heart Rhythm Management Centre, UZ Brussel-VUB, Brussels, Belgium
*
Correspondence to: M. C. Gonzalez Corcia, Pediatric Cardiology Department, Cliniques Universitaires St Luc, Avenue de Hippocrates 10, 1200, Brussels, Belgium. Tel: +00 322 764 1380; Fax: +02 764 8911; E-mail: maria.c.gonzalez@uclouvain.be
Get access Rights & Permissions [Opens in a new window]

Abstract

Brugada syndrome is an inherited arrhythmogenic disorder, characterised by coved-type ST-segment elevation in the right precordial leads, and is associated with increased risk of sudden death. It is genetically and clinically heterogeneous, presenting typically in the fourth or fifth decade of life. The prevalence of Brugada syndrome in the paediatric population is low compared with the adult population. Interestingly, over the last several years, there has been growing evidence in the literature of onset of the disease during childhood. Most of the paediatric cases reported in the literature consist of asymptomatic Brugada syndrome; however, some patients manifest the disease at different regions of the cardiac conduction system at a young age. Early expression of the disease can be affected by multiple factors, including genetic substrate, hormonal changes, and still unknown environmental exposures. The initial manifestation of Brugada syndrome in children can include sinus node dysfunction and atrial arrhythmias. Brugada syndrome can also manifest as ventricular arrhythmias leading to sudden death at an early age. In symptomatic children, performance of the ajmaline test by an experienced team can be safely used as a diagnostic tool to unmask latent Brugada syndrome. Defining indications for an implantable cardioverter defibrillator in children with the diagnosis of Brugada syndrome remains challenging. Given the rarity of the syndrome in children, most paediatric cardiologists will only rarely see a young patient with Brugada syndrome and there is still no universal consensus regarding the optimal management approach. Care should be individualised according to the specific clinical presentation, taking into account the family history, genetic data, and the family’s specific preferences.

Keywords

Brugada syndromesodium channel mutationssudden deathsudden infant death syndromesyncope
Type
Review Article
Information
Cardiology in the Young , Volume 26 , Issue 6 , August 2016 , pp. 1044 - 1055
Check for updates
Copyright
© Cambridge University Press 2016 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1 Brugada, P, Brugada, J. Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome: a multicenter report. J Am Coll Cardiol 1992; 20: 1391–1396.CrossRefGoogle ScholarPubMed
2 Wilde, AA, Antzelevitch, C, Borggrefe, M, et al. Proposed diagnostic criteria for the Brugada syndrome: consensus report. Circulation 2002; 106: 2514–2519.Google Scholar
3 Antzelevitch, C, Brugada, P, Borggrefe, M, et al. Brugada syndrome: report of the second consensus conference. Heart Rhythm 2005; 2: 429–440.Google ScholarPubMed
4 Hermida, JS, Lemoine, JL, Aoun, FB, Jarry, G, Ray, JL, Quiet, JC. Prevalence of the Brugada syndrome in an apparently healthy population. Am J Cardiol 2000; 86: 91–94.Google Scholar
5 Papadatos, GA, Wallerstein, PM, Head, CE, et al. Slowed conduction and ventricular tachycardia after targeted disruption of the cardiac sodium channel gene SCN5A. Proc Natl Acad Sci U S A 2002; 30: 6210–6215.Google Scholar
6 Kusano, K, Tanimaya, M, Nakamura, K. Atrial fibrillation in patients with Brugada syndrome: relationship of gene mutation, electrophysiology and clinical backgrounds. J Am Coll Cardiol 2008; 51: 1169–1175.Google Scholar
7 Francis, J, Antzelevitch, C. Atrial fibrillation and Brugada syndrome. J Am Coll Cardiol 2008; 51: 1149–1153.Google Scholar
8 Benson, DW, Wang, DW, Dyment, M, et al. Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A). J Clin Invest 2003; 112: 1019–1028.CrossRefGoogle ScholarPubMed
9 Nof, E, Gikson, M, Antzelevich, C. Genetic and sinus node dysfunction. J Atr Fibrillation 2009; 1: 328–336.Google Scholar
10 Letsas, KP, Korantzopoulos, P, Efremidis, M, et al. Sinus node disease in subjects with type 1 ECG pattern of Brugada syndrome. J Cardiol 2003; 61: 227–231.Google Scholar
11 Sumiyoshi, M, Nakazato, Y, Tokano, T, et al. Sinus node dysfunction concomitant with Brugada syndrome. Circ J 2005; 69: 946–950.Google Scholar
12 Davignon, A, Rautaharju, P, Boisselle, E, Soumis, F, Mégélas, M, Choquette, A. Normal ECG standards for infants and children. Ped Cardiol 1979/1980; 1: 123–131.Google Scholar
13 Conte, G, Dewals, W, Sieira, J, et al. Drug-induced Brugada syndrome in children: clinical features, device-based management, and long-term follow-up. J Am Coll Cardiol 2014; 63: 2272–2279.CrossRefGoogle ScholarPubMed
14 Makiyama, T, Akao, M, Tsuji, K, et al. High risk for bradyarrhythmic complications in patients with Brugada syndrome caused by SCN5A gene mutations. J Am Coll Cardiol 2005; 46: 2100–2106.Google Scholar
15 Lupoglazoff, JM, Cheav, T, Baroudi, G, et al. Homozygous SCN5A mutation in long-QT syndrome with functional two-to-one atrioventricular block. Circ Res. 2001; 89: E16–E21.Google Scholar
16 Kanter, RJ, Pjeiffer, R, Hu, D. Brugada-like syndrome in infancy presenting with rapid ventricular tachycardia and intraventricular conduction delay. Circulation 2012; 125: 14–22.Google Scholar
17 Roggen, A, Pavlovic, M, Pfammatter, JP. Frequency of spontaneous tachycardia in a pediatric population. Am J Cardiol 2008; 101: 852–854.Google Scholar
18 Yan, GX, Antzelevitch, C. Cellular basis for the Brugada syndrome and other mechanisms of arrhythmogenesis associated with ST-segment elevation. Circulation 1999; 100: 1660–1666.Google Scholar
19 Kim, G, Kyung, Y, Kang, I, et al. A pediatric case of Brugada syndrome diagnosed by fever-provoked ventricular tachycardia. Korean J Pediatr 2014; 57: 374–378.Google Scholar
20 Chockalingam, P, Rammeloo, L, Postema, P, et al. Fever-induced life-threatening arrhythmias in children harboring an SCN5A mutation. Pediatrics 2011; 127: e239–e244.Google Scholar
21 Miller, T, Estrella, E, Myerburg, R, et al. Recurrent third-trimester fetal loss and maternal mosaicism for long-QT syndrome. Circulation 2004; 109: 3029–3034.Google Scholar
22 Baruteau, A, Scheleich, JM. Antenatal presentation of congenital long QT syndrome: a prenatal diagnosis not to be missed. Pediatr Cardiol 2008; 29: 1131–1132.Google Scholar
23 AAP Task Force on infant positioning and SIDS. Positioning and SIDS. Pediatrics. 1992; 87: 1120–1126.Google Scholar
24 Moon, RY, Horne, RS, Hauck, FR. Sudden infant death syndrome. Lancet 2007; 370: 1578–1587.Google Scholar
25 Gutheroth, WG. Theories of cardiovascular causes in sudden infant death syndrome. J Am Coll Cardiol 1989; 14: 443–447.Google Scholar
26 Schwartz, PJ, Priori, SG, Bloise, R, et al. Molecular diagnosis in a child with sudden infant death syndrome. Lancet 2001; 358: 1342–1343.Google Scholar
27 Wedekind, H, Smits, JP, Schulze-Bahr, E, et al. De novo mutation in the SCN5A gene associated with early onset of sudden infant death. Circulation 2001; 104: 1158–1164.Google Scholar
28 Ackerman, MJ, Siu, BL, Stuner, WQ, et al. Postmortem molecular analysis of SCN5A defects in sudden infant death syndrome. JAMA 2001; 286: 2264–2269.Google Scholar
29 Wedekind, H, Smits, JPP, Schulze-Barh, E, et al. A de-novo mutation in the SCN5A gene associated with early onset of sudden infant death. Circulation 2001; 104: 1158–1164.Google Scholar
30 Skinner, JR, Chung, S-K, Montgomery, D, et al. Near-miss SIDS due to Brugada syndrome. Arch Dis Child 2005; 90: 528–529.Google Scholar
31 Priori, S, Napolitano, C, Giordano, U, et al. Brugada syndrome and sudden cardiac death in children. Lancet 2000; 355: 808–809.Google Scholar
32 Winkel, BG, Yuan, L, Olesen, M, et al. The role of the sodium current complex in a nonreferred nationwide cohort of sudden infant death syndrome. Heart Rhythm, 12: 1241–1249.CrossRefGoogle Scholar
33 Winkel, BG, Holst, AG, Theilade, J, et al. Nationwide study of sudden cardiac death in persons aged 1-35 years. Eur Heart J 2011; 32: 983–990.Google Scholar
34 Antzelevitch, C, Brugada, P, Borggrefe, M, et al. Brugada syndrome: report of the second consensus conference endorsed by Heart Rhythm Society and the European Heart Rhythm Association. Circulation 2005; 111: 659–660.Google Scholar
35 Di Diego, JM, Cordeiro, JM, Goodrow, RJ, et al. Ionic and cellular basis for the predominance of the Brugada syndrome phenotype in males. Circulation 2002; 106: 2004–2011.Google Scholar
36 Shimizu, W, Matsuo, K, Kokubo, Y, et al. Sex hormone and gender difference: role of testosterone on male predominance in Brugada syndrome. J Cardiovasc Electrophysiol 2007; 18: 415–421.Google Scholar
37 Allan, W, Gospe, S. Seizure, syncope, or breath-holding presenting to the pediatric neurologist – when is the etiology a life-threatening arrhythmia. Semin Pediatr Neurol 2005; 12: 2–9.Google Scholar
38 Kapplinger, JD, Tester, DJ, Alders, M, et al. An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing. Heart Rhythm 2010; 7: 33–46.Google Scholar
39 Dumaine, R, Towbin, JA, Brugada, P. Ionic mechanisms responsible for the electrocardiographic phenotype of the Brugada syndrome are temperature dependent. Circ Res 1999; 85: 803–809.Google Scholar
40 Waruiru, C, Appleton, R. Febrile seizures: an update. Arch Dis Child 2004; 89: 751–756.Google Scholar
41 Skinner, JR, Chung, SK, Nel, CA, et al. Brugada syndrome masquerading as febrile seizures. Pediatrics 2007; 119: e1206–e1211.CrossRefGoogle ScholarPubMed
42 Bayes de Luna, A, Brugada, J, Baranchuk, A, et al. Current electrocardiographic criteria for the diagnosis of Brugada pattern: a consensus report. J Electrocardiol 2012; 45: 433–442.Google Scholar
43 Rolf, S, Bruns, HJ, Wichter, T, et al. The ajmaline challenge in Brugada syndrome: diagnostic impact, safety, and recommended protocol. Eur Heart J 2003; 24: 1104–1112.Google Scholar
44 Veltmann, C, Wolpert, C, Sacher, F, et al. Response to intravenous ajmaline: a retrospective analysis of 677 ajmaline challenges. Europace 2009; 11: 1345–1352.Google Scholar
45 Samson, RA, Jolma, CD, Zamora, R. Normal values for corrected sinus node recovery time in adolescents. Pediatr Cardiol 1999; 20: 396–399.CrossRefGoogle ScholarPubMed
46 Yabek, S, Jarmakani, J, Robert, N. Sinus node function in children. Factors influencing its evaluation. Circulation 1976; 53: 28–33.Google Scholar
47 Semsarian, C, Ingles, J, Wilde, A. Sudden cardiac death in the young: the molecular autopsy and a practical approach to surviving relatives. Eur Heart J 2015; 3: 1–8.Google Scholar
48 Ackerman, MJ, Priori, SG, Willems, S, et al. HRS/EHRA Expert Consensus Statement on the state of genetic testing for channelopathies and cardiomyopathies. Heart Rhythm 2011; 8: 1308–1339.Google Scholar
49 Stephenson, EA, Batra, AS, Knilans, TK, et al. A multicenter experience with novel implantable cardioverter defibrillator configurations in the pediatric and congenital heart disease population. J Cardiovasc Electrophysiol 2006; 17: 41–46.CrossRefGoogle ScholarPubMed
50 Probst, V, Evain, S, Gournay, V, et al. Monomorphic ventricular tachycardia due to Brugada syndrome successfully treated by hydroquinidine therapy in a 3-year-old child. J Cardiovasc Electrophysiol 2006; 17: 97–100.Google Scholar
51 Hermida, JS, Denjoy, I, Clerc, J, et al. Hydroquinidine therapy in Brugada syndrome. J Am Coll Cardiol 2004; 43: 1853.Google Scholar
52 Nademanee, K, Veerakul, G, Mower, M, et al. Defibrillator versus beta-blocker for unexplained death in Thailand (DEBUT): a randomized clinical trial. Circulation 2003; 107: 2221–2226.Google Scholar
53 Priori, SG, Wilde, AA, Horie, M, et al. HRS/EHRA/APHRS Expert Consensus Statement on the diagnosis and management of patients with inherited primary arrhythmia syndrome. Heart Rhythm 2013; 29: e75–e106.Google Scholar
54 Probst, V, Denjoy, I, Meregalli, P, et al. Clinical aspects and prognosis of Brugada syndrome in children. Circulation 2007; 115: 2042–2048.Google Scholar
55 Mc Millan, MR, Day, TG, Batsota, M, et al. Feasibility and outcomes of ajmaline provocation testing for Brugada syndrome in children in a specialist paediatric inherited cardiovascular disease centre. Open Heart 2014; 12: 1–6.Google Scholar
56 Kaski, JP. Should we offer screening for Brugada syndrome in children? Card Rhythm News 2012; 9.Google Scholar
57 Harris, B, Miyake, C, Motonaga, K, et al. Diagnosis and management of pediatric Brugada syndrome: a survey of pediatric electrophysiologists. Pacing Clin Electrophysiol 2014; 37: 638–642.Google Scholar