Brugada Syndrome Associated with Different Heterozygous SCN5A Variants in Two Unrelated Families

Nadine Molitor; Argelia Medeiros-Domingo; Siv Fokstuen; Frank Ruschitzka; Firat Duru; Ardan Saguner

doi:10.3390/jcm11195625

Brugada Syndrome Associated with Different Heterozygous SCN5A Variants in Two Unrelated Families

J Clin Med. 2022 Sep 24;11(19):5625. doi: 10.3390/jcm11195625.

Authors

Nadine Molitor¹, Argelia Medeiros-Domingo², Siv Fokstuen^{1

3}, Frank Ruschitzka¹, Firat Duru^{1

4}, Ardan Saguner¹

Affiliations

¹ Department of Cardiology, University Heart Center Zurich, 8091 Zurich, Switzerland.
² Swiss DNAlysis, 8600 Dubendorf, Switzerland.
³ Genetic Medicine Division, Diagnostic Department, Hôpitaux Universitaires de Genève, 1205 Geneva, Switzerland.
⁴ Center for Integrative Human Physiology (ZIHP), University of Zurich, 8006 Zurich, Switzerland.

Abstract

The cardiac sodium channel (Nav1.5) controls cardiac excitability by triggering the action potential of cardiac myocytes and controlling electric impulse transmission. However, it has also been associated with arrhythmogenic cardiomyopathies. Accordingly, genetic variants in SCN5A that result in loss of function of Nav1.5 are associated with inherited arrhythmia syndromes, which are caused by reduced cardiac excitability, particularly Brugada syndrome (BrS) as well as arrhythmogenic right ventricular cardiomyopathy (ARVC). We report a novel pathogenic SCNA5 variant being associated with BrS overlapping with ARVC, as well as disease progression with a previously reported SCN5A variant being associated with a phenotype of BrS and conduction system disorder in two unrelated families.

Keywords: Brugada syndrome; SCN5A; arrhythmogenic right ventricular cardiomyopathy; channelopathy; overlapping syndrome.

Grants and funding

The Zurich ARVC Program is supported by the Georg und Bertha Schwyzer-Winiker Foundation, Baugarten Foundation, Wild Foundation, Swiss National Science Foundation (SNF), and the Swiss Heart Foundation.