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Brugada syndrome(SUNDS)

MedGen UID:
222975
Concept ID:
C1142166
Disease or Syndrome
Synonyms: Sudden unexpected nocturnal death syndrome; Sudden Unexplained Death Syndrome; Sudden unexplained nocturnal death syndrome; Sudden Unexplained Nocturnal Death Syndrome (SUNDS)
SNOMED CT: Brugada syndrome (418818005)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Related genes: SCN3B, GPD1L, HCN4, KCNE3, SCN5A, SCN1B, CACNB2, CACNA1C
 
Monarch Initiative: MONDO:0015263
OMIM®: 601144
OMIM® Phenotypic series: PS601144
Orphanet: ORPHA130

Disease characteristics

Excerpted from the GeneReview: Brugada Syndrome
Brugada syndrome is characterized by cardiac conduction abnormalities (ST segment abnormalities in leads V1-V3 on EKG and a high risk for ventricular arrhythmias) that can result in sudden death. Brugada syndrome presents primarily during adulthood, although age at diagnosis may range from infancy to late adulthood. The mean age of sudden death is approximately 40 years. Clinical presentations may also include sudden infant death syndrome (SIDS; death of a child during the first year of life without an identifiable cause) and sudden unexpected nocturnal death syndrome (SUNDS), a typical presentation in individuals from Southeast Asia. Other conduction defects can include first-degree AV block, intraventricular conduction delay, right bundle branch block, and sick sinus syndrome. [from GeneReviews]
Authors:
Ramon Brugada  |  Oscar Campuzano  |  Georgia Sarquella-Brugada, et. al.   view full author information

Additional descriptions

From OMIM
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 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 Genetics
Brugada 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

Professional guidelines

PubMed

Espinosa Á, Ripollés-Melchor J, Brugada R, Campuzano Ó, Sarquella-Brugada G, Abad-Motos A, Zaballos-García M, Abad-Torrent A, Prieto-Gundin A, Brugada J
Minerva Anestesiol 2019 Feb;85(2):173-188. Epub 2018 Oct 30 doi: 10.23736/S0375-9393.18.13170-1. PMID: 30394071
Gourraud JB, Barc J, Thollet A, Le Marec H, Probst V
Arch Cardiovasc Dis 2017 Mar;110(3):188-195. Epub 2017 Jan 27 doi: 10.1016/j.acvd.2016.09.009. PMID: 28139454
Baranchuk A, Enriquez A, García-Niebla J, Bayés-Genís A, Villuendas R, Bayés de Luna A
Ann Noninvasive Electrocardiol 2015 Jan;20(1):7-17. Epub 2014 Dec 26 doi: 10.1111/anec.12241. PMID: 25546557Free PMC Article

Suggested Reading

PubMed

Priori SG, Wilde AA, Horie M, Cho Y, Behr ER, Berul C, Blom N, Brugada J, Chiang CE, Huikuri H, Kannankeril P, Krahn A, Leenhardt A, Moss A, Schwartz PJ, Shimizu W, Tomaselli G, Tracy C; Document Reviewers, Ackerman M, Belhassen B, Estes NA 3rd, Fatkin D, Kalman J, Kaufman E, Kirchhof P, Schulze-Bahr E, Wolpert C, Vohra J, Refaat M, Etheridge SP, Campbell RM, Martin ET, Quek SC; Heart Rhythm Society; European Heart Rhythm Association; Asia Pacific Heart Rhythm Society
Europace 2013 Oct;15(10):1389-406. Epub 2013 Aug 30 doi: 10.1093/europace/eut272. PMID: 23994779

Recent clinical studies

Etiology

Krahn AD, Behr ER, Hamilton R, Probst V, Laksman Z, Han HC
JACC Clin Electrophysiol 2022 Mar;8(3):386-405. doi: 10.1016/j.jacep.2021.12.001. PMID: 35331438
Marsman EMJ, Postema PG, Remme CA
Heart 2022 May;108(9):668-675. Epub 2021 Oct 14 doi: 10.1136/heartjnl-2020-318258. PMID: 34649929
Espinosa Á, Ripollés-Melchor J, Brugada R, Campuzano Ó, Sarquella-Brugada G, Abad-Motos A, Zaballos-García M, Abad-Torrent A, Prieto-Gundin A, Brugada J
Minerva Anestesiol 2019 Feb;85(2):173-188. Epub 2018 Oct 30 doi: 10.23736/S0375-9393.18.13170-1. PMID: 30394071
Brugada J, Campuzano O, Arbelo E, Sarquella-Brugada G, Brugada R
J Am Coll Cardiol 2018 Aug 28;72(9):1046-1059. doi: 10.1016/j.jacc.2018.06.037. PMID: 30139433
Gourraud JB, Barc J, Thollet A, Le Marec H, Probst V
Arch Cardiovasc Dis 2017 Mar;110(3):188-195. Epub 2017 Jan 27 doi: 10.1016/j.acvd.2016.09.009. PMID: 28139454

Diagnosis

Korlipara H, Korlipara G, Pentyala S
Acta Cardiol 2021 Oct;76(8):805-824. Epub 2020 Jul 20 doi: 10.1080/00015385.2020.1790823. PMID: 32684122
Espinosa Á, Ripollés-Melchor J, Brugada R, Campuzano Ó, Sarquella-Brugada G, Abad-Motos A, Zaballos-García M, Abad-Torrent A, Prieto-Gundin A, Brugada J
Minerva Anestesiol 2019 Feb;85(2):173-188. Epub 2018 Oct 30 doi: 10.23736/S0375-9393.18.13170-1. PMID: 30394071
Brugada J, Campuzano O, Arbelo E, Sarquella-Brugada G, Brugada R
J Am Coll Cardiol 2018 Aug 28;72(9):1046-1059. doi: 10.1016/j.jacc.2018.06.037. PMID: 30139433
Gourraud JB, Barc J, Thollet A, Le Marec H, Probst V
Arch Cardiovasc Dis 2017 Mar;110(3):188-195. Epub 2017 Jan 27 doi: 10.1016/j.acvd.2016.09.009. PMID: 28139454
Fu DG
Cell Biochem Biophys 2015 Nov;73(2):291-296. doi: 10.1007/s12013-015-0626-4. PMID: 25737133

Therapy

Krahn AD, Behr ER, Hamilton R, Probst V, Laksman Z, Han HC
JACC Clin Electrophysiol 2022 Mar;8(3):386-405. doi: 10.1016/j.jacep.2021.12.001. PMID: 35331438
Gourraud JB, Barc J, Thollet A, Le Marec H, Probst V
Arch Cardiovasc Dis 2017 Mar;110(3):188-195. Epub 2017 Jan 27 doi: 10.1016/j.acvd.2016.09.009. PMID: 28139454
Vandael E, Vandenberk B, Vandenberghe J, Willems R, Foulon V
Int J Clin Pharm 2017 Feb;39(1):16-25. Epub 2016 Dec 23 doi: 10.1007/s11096-016-0414-2. PMID: 28012118
Fu DG
Cell Biochem Biophys 2015 Nov;73(2):291-296. doi: 10.1007/s12013-015-0626-4. PMID: 25737133
Kloesel B, Ackerman MJ, Sprung J, Narr BJ, Weingarten TN
Can J Anaesth 2011 Sep;58(9):824-36. Epub 2011 Jun 23 doi: 10.1007/s12630-011-9546-y. PMID: 21698509

Prognosis

Stiles MK, Wilde AAM, Abrams DJ, Ackerman MJ, Albert CM, Behr ER, Chugh SS, Cornel MC, Gardner K, Ingles J, James CA, Jimmy Juang JM, Kääb S, Kaufman ES, Krahn AD, Lubitz SA, MacLeod H, Morillo CA, Nademanee K, Probst V, Saarel EV, Sacilotto L, Semsarian C, Sheppard MN, Shimizu W, Skinner JR, Tfelt-Hansen J, Wang DW
Heart Rhythm 2021 Jan;18(1):e1-e50. Epub 2020 Oct 19 doi: 10.1016/j.hrthm.2020.10.010. PMID: 33091602Free PMC Article
Korlipara H, Korlipara G, Pentyala S
Acta Cardiol 2021 Oct;76(8):805-824. Epub 2020 Jul 20 doi: 10.1080/00015385.2020.1790823. PMID: 32684122
Gourraud JB, Barc J, Thollet A, Le Marec H, Probst V
Arch Cardiovasc Dis 2017 Mar;110(3):188-195. Epub 2017 Jan 27 doi: 10.1016/j.acvd.2016.09.009. PMID: 28139454
Jellins J, Milanovic M, Taitz DJ, Wan SH, Yam PW
Hong Kong Med J 2013 Apr;19(2):159-67. PMID: 23535677
Benito B, Brugada J, Brugada R, Brugada P
Rev Esp Cardiol 2009 Nov;62(11):1297-315. doi: 10.1016/s1885-5857(09)73357-2. PMID: 19889341

Clinical prediction guides

Marsman EMJ, Postema PG, Remme CA
Heart 2022 May;108(9):668-675. Epub 2021 Oct 14 doi: 10.1136/heartjnl-2020-318258. PMID: 34649929
Korlipara H, Korlipara G, Pentyala S
Acta Cardiol 2021 Oct;76(8):805-824. Epub 2020 Jul 20 doi: 10.1080/00015385.2020.1790823. PMID: 32684122
Glazer AM, Wada Y, Li B, Muhammad A, Kalash OR, O'Neill MJ, Shields T, Hall L, Short L, Blair MA, Kroncke BM, Capra JA, Roden DM
Am J Hum Genet 2020 Jul 2;107(1):111-123. Epub 2020 Jun 12 doi: 10.1016/j.ajhg.2020.05.015. PMID: 32533946Free PMC Article
Brugada J, Campuzano O, Arbelo E, Sarquella-Brugada G, Brugada R
J Am Coll Cardiol 2018 Aug 28;72(9):1046-1059. doi: 10.1016/j.jacc.2018.06.037. PMID: 30139433
Gourraud JB, Barc J, Thollet A, Le Marec H, Probst V
Arch Cardiovasc Dis 2017 Mar;110(3):188-195. Epub 2017 Jan 27 doi: 10.1016/j.acvd.2016.09.009. PMID: 28139454

Recent systematic reviews

Mascia G, Della Bona R, Ameri P, Canepa M, Porto I, Brignole M
J Cardiovasc Electrophysiol 2020 Dec;31(12):3334-3338. Epub 2020 Nov 1 doi: 10.1111/jce.14787. PMID: 33090608
Tse G, Lee S, Gong M, Mililis P, Asvestas D, Bazoukis G, Roever L, Jeevaratnam K, Hothi SS, Li KHC, Liu T, Letsas KP
J Interv Card Electrophysiol 2020 Mar;57(2):319-327. Epub 2019 Dec 14 doi: 10.1007/s10840-019-00675-z. PMID: 31836966
Rattanawong P, Riangwiwat T, Prasitlumkum N, Limpruttidham N, Kanjanahattakij N, Chongsathidkiet P, Vutthikraivit W, Chung EH
Ann Noninvasive Electrocardiol 2018 Mar;23(2):e12507. Epub 2017 Oct 14 doi: 10.1111/anec.12507. PMID: 29030919Free PMC Article
Vandael E, Vandenberk B, Vandenberghe J, Willems R, Foulon V
Int J Clin Pharm 2017 Feb;39(1):16-25. Epub 2016 Dec 23 doi: 10.1007/s11096-016-0414-2. PMID: 28012118
Masrur S, Memon S, Thompson PD
Clin Cardiol 2015 May;38(5):323-6. Epub 2015 May 8 doi: 10.1002/clc.22386. PMID: 25955277Free PMC Article

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