Brugada Syndrome 1; Brgda1

Description

Brugada syndrome is characterized by an ST segment elevation in the right precordial electrocardiogram leads (so-called type 1 ECG) and a high incidence of sudden death in patients with structurally normal hearts. The syndrome typically manifests during adulthood, with a mean age of sudden death of 41 +/- 15 years, but also occurs in infants and children (summary by Antzelevitch et al., 2005). Genetic Heterogeneity of Brugada SyndromeBrugada syndrome-2 (OMIM ) is caused by mutation in the GPD1L gene (OMIM ) on chromosome 3p22. Brugada syndrome-3 (OMIM ) and Brugada syndrome-4 (OMIM ), the phenotypes of which include a shortened QT interval on ECG, are caused by mutation in the CACNA1C gene (OMIM ) on chromosome 12p13 and CACNB2 gene (OMIM ) on chromosome 10p12, respectively. Brugada syndrome-5 (OMIM ) is caused by mutation in the SCN1B gene (OMIM ) on chromosome 19q13. Brugada syndrome-6 (OMIM ) is caused by mutation in the KCNE3 gene (OMIM ) on chromosome 11q13. Brugada syndrome-7 (OMIM ) is caused by mutation in the SCN3B gene (OMIM ) on chromosome 11q24. Brugada syndrome-8 (OMIM ) is caused by mutation in the HCN4 gene (OMIM ) on chromosome 15q24. Brugada syndrome-9 (OMIM ) is caused by mutation in the KCND3 gene (OMIM ) on chromosome 1p13.Antzelevitch et al. (2007) screened 82 consecutive probands with a clinical diagnosis of Brugada syndrome for mutations in 16 ion channel genes. Seven probands were found to have mutations in the CACNA1C (OMIM ) or CACNB2 (OMIM ) genes, including 3 Brugada probands with shortened QTc intervals (see {611875} and {611876}). Fifteen percent of probands harbored a pathogenic mutation in the SCN5A gene.Delpon et al. (2008) screened 14 ion channel genes in 105 probands with Brugada syndrome and detected SCN5A mutations in 14.3%, CACNA1C mutations in 6.7%, and CACNB2 mutations in 4.8% of the probands.Hu et al. (2009) analyzed 9 'Brugada susceptibility' genes, including SCN5A, GPD1L (OMIM ), CACNB2, CACNA1C, SCN1B (OMIM ), KCNE2 (OMIM ), KCNE3 (OMIM ), KCNE4 (OMIM ), and IRX5 (OMIM ), as well as the sodium channel beta subunit SCN3B (OMIM ), in 179 probands with Brugada syndrome; they noted that 129 (72.07%) of the probands were negative for mutation in all of the genes tested.Crotti et al. (2012) analyzed 12 Brugada syndrome susceptibility genes in 129 unrelated patients with possible or probable Brugada syndrome and identified SCN5A mutations in 21 (16.3%) of the patients; only 6 (4.6%) of the patients carried a mutation in 1 of the other 11 genes.In a cohort of 91 SCN5A-negative Brugada syndrome patients and 91 European controls from the 1000 Genomes Project database, Di Resta et al. (2015) analyzed 158 arrhythmia- and cardiac defect-associated genes. A significant enrichment in Brugada syndrome samples was found only for the DSG2 gene (OMIM ), with 6 (6%) of 91 patients having a rare functional variant compared to none of the 91 controls (p = 0.029). In addition, borderline significance was detected for the MYH7 gene (OMIM ) (5 patients versus 0 controls; p = 0.059). Analysis of phenotype correlations yielded statistical significance only between the presence of a DSG2 variant and syncope, documented ventricular tachycardia/fibrillation, and/or cardiac arrest (p = 0.034). Di Resta et al. (2015) noted the possible genetic overlap between different cardiac disorders, suggesting common pathogenetic pathways.

Clinical Features

• Fever
• Respiratory distress
• Arrhythmia
• Abnormal heart morphology
• Tachycardia
• Sudden cardiac death
• Syncope
• Cardiac arrest
• Ventricular tachycardia
• Ventricular arrhythmia

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