From OMIMBrugada 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 Syndrome
Brugada syndrome-2 (611777) is caused by mutation in the GPD1L gene (611778) on chromosome 3p22. Brugada syndrome-3 (611875) and Brugada syndrome-4 (611876), the phenotypes of which include a shortened QT interval on ECG, are caused by mutation in the CACNA1C gene (114205) on chromosome 12p13 and CACNB2 gene (600003) on chromosome 10p12, respectively. Brugada syndrome-5 (612838) is caused by mutation in the SCN1B gene (600235) on chromosome 19q13. Brugada syndrome-6 (613119) is caused by mutation in the KCNE3 gene (604433) on chromosome 11q13. Brugada syndrome-7 (613120) is caused by mutation in the SCN3B gene (608214) on chromosome 11q24. Brugada syndrome-8 (613123) is caused by mutation in the HCN4 gene (605206) on chromosome 15q24. Brugada syndrome-9 (616399) is caused by mutation in the KCND3 gene (605411) on chromosome 1p13.
Hosseini et al. (2018) described a study to evaluate the clinical validity of 21 genes tested by diagnostic laboratories for Brugada syndrome. Using an evidence-based semiquantitative scoring system of genetic and experimental evidence, 3 curation teams independently classified genes as demonstrating limited to definitive evidence. The classifications were then reviewed by an expert panel for consensus. Based on the expert panel review, only one of the genes, SCN5A, was classified as having definitive evidence as a cause of Brugada syndrome.
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 (114205) or CACNB2 (600003) 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 (611778), CACNB2, CACNA1C, SCN1B (600235), KCNE2 (603796), KCNE3 (604433), KCNE4 (607775), and IRX5 (606195), as well as the sodium channel beta subunit SCN3B (608214), 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 (125671), 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 (160760) (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.
http://www.omim.org/entry/601144 From MedlinePlus GeneticsBrugada syndrome is a condition that causes a disruption of the heart's normal rhythm. Specifically, this disorder can lead to irregular heartbeats in the heart's lower chambers (ventricles), which is an abnormality called ventricular arrhythmia. If untreated, the irregular heartbeats can cause fainting (syncope), seizures, difficulty breathing, or sudden death. These complications typically occur when an affected person is resting or asleep.
Brugada syndrome usually becomes apparent in adulthood, although it can develop any time throughout life. Signs and symptoms related to arrhythmias, including sudden death, can occur from early infancy to late adulthood. Sudden death typically occurs around age 40. This condition may explain some cases of sudden infant death syndrome (SIDS), which is a major cause of death in babies younger than 1 year. SIDS is characterized by sudden and unexplained death, usually during sleep.
Sudden unexplained nocturnal death syndrome (SUNDS) is a condition characterized by unexpected cardiac arrest in young adults, usually at night during sleep. This condition was originally described in Southeast Asian populations, where it is a major cause of death. Researchers have determined that SUNDS and Brugada syndrome are the same disorder.
https://medlineplus.gov/genetics/condition/brugada-syndrome