Abstract
Brugada syndrome (BrS) is an inherited disorder with high allelic and genetic heterogeneity clinically characterized by typical coved-type ST segment elevation at the electrocardiogram (ECG), which may occur either spontaneously or after provocative drug testing. BrS is classically described as an arrhythmic condition occurring in a structurally normal heart and is associated with the risk of ventricular fibrillation and sudden cardiac death (SCD). We studied five patients with spontaneous or drug-induced type 1 ECG pattern, variably associated with symptoms and a positive family history through a Next Generation Sequencing panels approach, which includes genes of both channelopathies and cardiomyopathies. We identified variants in MYBPC3 and in MYH7, hypertrophic cardiomyopathy (HCM) genes (MYBPC3: p.Lys1065Glnfs*12 and c.1458-1G > A, MYH7: p.Arg783His, p.Val1213Met, p.Lys744Thr). Our data propose that Brugada type 1 ECG may be an early electrocardiographic marker of a concealed structural heart disease, possibly enlarging the genotypic overlap between Brugada syndrome and cardiomyopathies.
Highlights
A typical ECG pattern, characterized by a coved ST-segment elevation ≥ 2 mm in at least one right precordial lead followed by a concave or straight ST segment elevation and a negative symmetric T-wave [1], is associated with Brugada syndrome, an inherited disease characterized by an increased risk of ventricular arrhythmias and sudden cardiac death (SCD) in a structurally normal heart [2]
Among a cohort of 51 patients with BrP tested by the gene panel including both structural and arrhythmogenic cardiomyopathies, we identified five patients carrying a pathogenic/likely pathogenic variation in sarcomeric genes
The phenotypic and genotypic overlap between Brugada syndrome (BrS) and arrhythmogenic cardiomyopathy (ACM) is well-known in literature and it is supported by the identification of both conduction abnormalities and structural alterations in the right ventricular outflow tract (RVOT) in BrS patients [14,22,23,24]
Summary
A typical ECG pattern, characterized by a coved ST-segment elevation ≥ 2 mm in at least one right precordial lead followed by a concave or straight ST segment elevation and a negative symmetric T-wave [1], is associated with Brugada syndrome, an inherited disease characterized by an increased risk of ventricular arrhythmias and sudden cardiac death (SCD) in a structurally normal heart [2]. BrS is complicated by many confounding factors: genetic and allelic heterogeneity, variants of uncertain significance [11], incomplete penetrance [12], phenotypic overlaps [6] and new evidence of complex inheritance [12] and mutation load [13], overcoming the one gene–one disease paradigm [10]. The overlap between BrS and arrhythmogenic cardiomyopathy (ACM) is well known in the literature, so much that ACM and BrS could be seen as two different entities belonging to the same disease spectrum [10,14]
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