Brugada syndrome: current concepts and genetic background

Authors

  • Andrés Ricardo Pérez-Riera Laboratório de Delineamento de Estudos e Escrita Científica. Centro Universitário FMABC, Santo André, São Paulo, Brazil.
  • Joseane Elza Tonussi Mendes Laboratório de Delineamento de Estudos e Escrita Científica. Centro Universitário FMABC, Santo André, São Paulo, Brazil.
  • Fabiola Ferreira da Silva Laboratório de Delineamento de Estudos e Escrita Científica. Centro Universitário FMABC, Santo André, São Paulo, Brazil.
  • Frank Yanowitz Intermountain Medical Center, Intermountain Heart Institute, Salt Lake City, UT, United States; The University of Utah, Department of Internal Medicine, Salt Lake City, UT, United States
  • Luiz Carlos de Abreu Professor. Department of Integrated Health Education and Graduate Program in Collective Health. Federal University of Espírito Santo, ES, Brazil.
  • José Luiz Figueiredo Department of Surgery, Experimental Surgery Unit, Federal University of Pernambuco, Recife, Pernambuco, Brazil.
  • Rodrigo Daminello Raimundo Laboratório de Delineamento de Estudos e Escrita Científica. Centro Universitário FMABC, Santo André, São Paulo, Brazil.
  • Raimundo Barbosa-Barros Coronary Center of the Hospital de Messejana Dr. Carlos Alberto Studart Gomes, Fortaleza, Ceará, Brazil
  • Kjell Nikus Heart Center, Tampere University Hospital and Faculty of Medicine and Health Technology, Tampere University, Finland.
  • Pedro Brugada Scientific Director, Cardiovascular Division, Free University of Brussels (UZ Brussel) VUB, Brussels, Belgium

DOI:

https://doi.org/10.36311/jhgd.v31.11074

Keywords:

Brugada Syndrome, arrhythmic, environmental, genotype, phenotyp

Abstract

Brugada syndrome (BrS) is a hereditary clinical-electrocardiographic arrhythmic entity with low worldwide prevalence. The syndrome is caused by changes in the structure and function of certain cardiac ion channels and reduced expression of Connexin 43 (Cx43) in the Right Ventricle (RV), predominantly in the Right Ventricular Outflow Tract (VSVD), causing electromechanical abnormalities. The diagnosis is based on the presence of spontaneous or medicated ST elevation, characterized by boost of the J point and the ST segment ≥2 mm, of superior convexity "hollow type" (subtype 1A) or descending rectilinear model (subtype 1B). BrS is associated with an increased risk of syncope, palpitations, chest pain, convulsions, difficulty in breathing (nocturnal agonal breathing) and/or Sudden Cardiac Death (SCD) secondary to PVT/VF, unexplained cardiac arrest or documented PVT/VF or Paroxysmal atrial fibrillation (AF) in the absence of apparent macroscopic or structural heart disease, electrolyte disturbance, use of certain medications or coronary heart disease and fever. In less than three decades since the discovery of Brugada syndrome, the concept of Mendelian heredity has come undone. The enormous variants and mutations found mean that we are still far from being able to concretely clarify a genotype-phenotype relationship. There is no doubt that the entity is oligogenetic, associated with environmental factors, and that there are variants of uncertain significance, especially the rare variants of the SCN5A mutation, with European or Japanese ancestors, as well as a spontaneous type 1 or induced pattern, thanks to gnomAD (coalition) researchers who seek to aggregate and harmonize exome and genome sequencing data from a variety of large scale sequencing projects and make summary data available to the scientific community at large). Thus, we believe that this in depth analytical study of the countless mutations attributed to BrS may constitute a real cornerstone that will help to better understand this intriguing syndrome.

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References

Monasky MM, Micaglio E, Ciconte G, Pappone C. Brugada syndrome: oligogenic or mendelian disease? International Journal of Molecular Sciences. janeiro de 2020; 21(5): 1687.

Wang Q, Ohno S, Ding W-G, Fukuyama M, Miyamoto A, Itoh H, et al. Gain-of-function kcnh2 mutations in patients with brugada syndrome: novel kcnh2 mutations in brugada syndrome. J Cardiovasc Electrophysiol. maio de 2014; 25(5): 522–30.

Published

2021-03-31

Issue

Section

ORIGINAL ARTICLES