Brugada syndrome

General Information (adopted from Orphanet):

Synonyms, Signs: SUNDS
Pokkuri death syndrome
Sudden unexplained nocturnal death syndrome
Idiopathic ventricular fibrillation, Brugada type
Dream disease
Bangungut
Number of Symptoms 25
OrphanetNr: 130
OMIM Id: 601144
611777
611875
611876
612838
613119
613120
613123
ICD-10: I47.2
UMLs: C1142166
MeSH: D053840
MedDRA: 10059027
Snomed: 418818005

Prevalence, inheritance and age of onset:

Prevalence: 50 of 100 000 - PMID: 19889341 [IBIS]
Inheritance: Autosomal dominant
- PMID: 27082542 [IBIS]
Age of onset: Childhood
Adult
- PMID: 27151277 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Genetic cardiac rhythm disease
 -Rare cardiac disease
 -Rare genetic disease

Comment:

Brugada syndrome is an inherited cardiac arrhythmia syndrome electrographically characterized by distinct coved type ST segment elevation in the right pericordial leads (V1–V3). The syndrome preferentially manifests in the third to fourth decade of life and is associated with a high risk for sudden cardiac death. There are several conditions that produce Brugada-like symptoms including right bundle branch block, Friedreich's ataxia or Chagas disease. Men are 8 to 10 times more frequently affected than women. Implantable cardioverter defibrillator is the most common accepted therapeutic option. (PMID: 26671757) Up to now 19 genes have been identified to be associated with Brugada syndrome and all of them are involved in the regulation of ion channels. According to the affected gene, the disease is subdivided into 19 sub-types. SNC5A, responsible for Brugada syndorme, type 1 (BRGDA1), is the most common Brugada syndrome-causing gene.

Symptom Information: Sort by abundance 

1
(HPO:0011702) Abnormal electrophysiology of sinoatrial node origin 27151277 IBIS 4 / 7739
2
(OMIM) Sinus node dysfunction 27151277 IBIS 3 / 7739
3
(HPO:0004308) Ventricular arrhythmia Frequent [IBIS] 19889341 IBIS 46 / 7739
4
(HPO:0011675) Arrhythmia 16643399 IBIS 226 / 7739
5
(HPO:0100749) Chest pain 24581105 IBIS 92 / 7739
6
(HPO:0004756) Ventricular tachycardia Occasional [IBIS] 4.2% (n=834) 26538325 IBIS 55 / 7739
7
(HPO:0001279) Syncope Occasional [IBIS] 24.5% (n=542) 26740482 IBIS 94 / 7739
8
(HPO:0012251) ST segment elevation Frequent [IBIS] 26671757 IBIS 7 / 7739
9
(HPO:0003115) Abnormal EKG 26671757 IBIS 44 / 7739
10
(HPO:0012248) Prolonged PR interval Frequent [IBIS] 26671757; 24998131 IBIS 6 / 7739
11
(HPO:0005115) Supraventricular arrhythmia 26671757 IBIS 13 / 7739
12
(HPO:0005110) Atrial fibrillation 26671757 IBIS 71 / 7739
13
(HPO:0004749) Atrial flutter 26671757 IBIS 20 / 7739
14
(HPO:0004309) Ventricular preexcitation 26671757 IBIS 6 / 7739
15
(HPO:0011712) Right bundle branch block Occasional [IBIS] 7.7% (n=326) 26447120 IBIS 34 / 7739
16
(HPO:0001692) Primary atrial arrhythmia Occasional [IBIS] 26671757 IBIS 16 / 7739
17
(HPO:0001645) Sudden cardiac death Occasional [IBIS] 4.2% (n=542) 26740482 IBIS 84 / 7739
18
(HPO:0001657) Prolonged QT interval 26671757; 14607451 IBIS 33 / 7739
19
(HPO:0001663) Ventricular fibrillation 26671757 IBIS 35 / 7739
20
(HPO:0012272) J wave 26671757 IBIS 3 / 7739
21
(HPO:0001962) Palpitations 26671757 IBIS 62 / 7739
22
(HPO:0011717) AV nodal reentry tachycardia 26671757 IBIS 2 / 7739
23
(HPO:0006677) Prolonged QRS complex Frequent [IBIS] 26671757; 24998131 IBIS 16 / 7739
24
(HPO:0006543) Cardiorespiratory arrest 26671757 IBIS 11 / 7739
25
(MedDRA:10050380) Electrocardiogram T wave abnormal 26671757 IBIS 5 / 7739

Associated genes:

SCN5A; GPD1-L; CACNA1C; CACNB2; SCN1B; KCNE3; SCN3B; KCNJ8; CACNA2D1; KCND3; RANGRF; SLMAP; ABCC9; SCN2B; PKP2; FGF12; SCN10A; HEY2; SEMA3A;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference
CACNA1C rs121912775 pathogenic RCV000058286.2
CACNA1C rs121912775 pathogenic RCV000019201.29
CACNA1C rs121912776 pathogenic RCV000058283.2
CACNA1C rs121912776 pathogenic RCV000019202.29
CACNA1C rs199473391 pathogenic RCV000058287.2
CACNA1C rs199473392 pathogenic RCV000058290.2
CACNA1C rs199473660 pathogenic RCV000058289.2
CACNB2 rs121917812 pathogenic RCV000010155.3
CACNB2 rs587777742 pathogenic RCV000144246.4
GPD1L rs72552291 pathogenic RCV000000822.5
GPD1L rs72552292 pathogenic RCV000000823.3
GPD1L rs72552293 pathogenic RCV000000824.2
GPD1L rs72552294 pathogenic RCV000000825.2
KCND3 rs150401343 pathogenic RCV000172842.2
KCND3 rs786205867 pathogenic RCV000172844.2
KCNE3 rs121908441 pathogenic RCV000005880.3
SCN1B rs267607028 pathogenic RCV000009836.4
SCN3B rs121918282 pathogenic RCV000002574.8
SCN3B rs121918282 likely pathogenic RCV000171567.1
SCN5A rs137854601 pathogenic RCV000009973.2
SCN5A rs137854602 pathogenic RCV000009977.2
SCN5A rs137854603 pathogenic RCV000009978.2
SCN5A rs137854603 pathogenic RCV000058806.2
SCN5A rs137854604 likely pathogenic RCV000197520.1
SCN5A rs137854609 pathogenic RCV000058541.2
SCN5A rs137854609 likely pathogenic RCV000171570.2
SCN5A rs137854611 pathogenic RCV000058487.2
SCN5A rs137854611 pathogenic RCV000058488.2
SCN5A rs137854611 pathogenic RCV000009989.3
SCN5A rs137854612 pathogenic RCV000058649.2
SCN5A rs137854612 pathogenic RCV000009996.2
SCN5A rs137854615 pathogenic RCV000058777.2
SCN5A rs137854615 pathogenic RCV000009999.2
SCN5A rs137854616 pathogenic RCV000010001.2
SCN5A rs137854616 pathogenic RCV000058602.2
SCN5A rs137854617 pathogenic RCV000010002.2
SCN5A rs137854618 pathogenic RCV000058604.2
SCN5A rs137854620 pathogenic RCV000010006.4
SCN5A rs185492581 pathogenic RCV000058601.2
SCN5A rs193922726 pathogenic RCV000058750.2
SCN5A rs199473042 pathogenic RCV000058735.2
SCN5A rs199473050 pathogenic RCV000058481.2
SCN5A rs199473051 pathogenic RCV000058505.2
SCN5A rs199473052 pathogenic RCV000058528.2
SCN5A rs199473053 pathogenic RCV000058530.2
SCN5A rs199473054 pathogenic RCV000058531.2
SCN5A rs199473055 pathogenic RCV000058549.2
SCN5A rs199473056 pathogenic RCV000058560.2
SCN5A rs199473058 pathogenic RCV000058583.2
SCN5A rs199473061 pathogenic RCV000058666.2
SCN5A rs199473062 pathogenic RCV000058710.2
SCN5A rs199473062 pathogenic RCV000058711.2
SCN5A rs199473063 pathogenic RCV000058757.2
SCN5A rs199473065 pathogenic RCV000058772.2
SCN5A rs199473066 pathogenic RCV000058781.2
SCN5A rs199473067 pathogenic RCV000058792.2
SCN5A rs199473070 pathogenic RCV000058829.2
SCN5A rs199473074 pathogenic RCV000058838.2
SCN5A rs199473076 pathogenic RCV000058842.2
SCN5A rs199473079 pathogenic RCV000058845.2
SCN5A rs199473081 pathogenic RCV000058848.2
SCN5A rs199473082 pathogenic RCV000058850.2
SCN5A rs199473083 pathogenic RCV000144028.2
SCN5A rs199473083 pathogenic RCV000058851.2
SCN5A rs199473085 pathogenic RCV000058856.2
SCN5A rs199473086 pathogenic RCV000058857.2
SCN5A rs199473088 pathogenic RCV000058860.2
SCN5A rs199473089 pathogenic RCV000058863.2
SCN5A rs199473090 pathogenic RCV000058864.2
SCN5A rs199473091 pathogenic RCV000058865.2
SCN5A rs199473092 pathogenic RCV000058866.2
SCN5A rs199473093 pathogenic RCV000058379.2
SCN5A rs199473095 pathogenic RCV000058386.2
SCN5A rs199473095 pathogenic RCV000058385.2
SCN5A rs199473096 pathogenic RCV000058387.2
SCN5A rs199473098 pathogenic RCV000058392.2
SCN5A rs199473101 pathogenic RCV000058396.2
SCN5A rs199473102 pathogenic RCV000058397.2
SCN5A rs199473103 pathogenic RCV000058400.2
SCN5A rs199473104 pathogenic RCV000058399.2
SCN5A rs199473117 pathogenic RCV000058425.2
SCN5A rs199473118 pathogenic RCV000144029.2
SCN5A rs199473122 pathogenic RCV000058436.2
SCN5A rs199473123 likely pathogenic RCV000058439.2
SCN5A rs199473124 pathogenic RCV000058442.2
SCN5A rs199473129 pathogenic RCV000058451.2
SCN5A rs199473133 pathogenic RCV000058457.2
SCN5A rs199473134 pathogenic RCV000058459.2
SCN5A rs199473137 pathogenic RCV000058464.2
SCN5A rs199473139 pathogenic RCV000058470.2
SCN5A rs199473143 pathogenic RCV000058474.2
SCN5A rs199473144 pathogenic RCV000058475.2
SCN5A rs199473149 pathogenic RCV000058484.2
SCN5A rs199473151 pathogenic RCV000058486.2
SCN5A rs199473154 pathogenic RCV000058492.2
SCN5A rs199473156 pathogenic RCV000058494.2
SCN5A rs199473158 pathogenic RCV000058496.2
SCN5A rs199473159 pathogenic RCV000058498.2
SCN5A rs199473163 pathogenic RCV000058504.2
SCN5A rs199473164 pathogenic RCV000058506.2
SCN5A rs199473167 pathogenic RCV000058512.2
SCN5A rs199473168 pathogenic RCV000058513.2
SCN5A rs199473169 pathogenic RCV000058515.2
SCN5A rs199473170 pathogenic RCV000058516.2
SCN5A rs199473171 pathogenic RCV000058517.2
SCN5A rs199473172 pathogenic RCV000058518.2
SCN5A rs199473173 pathogenic RCV000058519.2
SCN5A rs199473174 pathogenic RCV000058521.2
SCN5A rs199473175 pathogenic RCV000058522.2
SCN5A rs199473176 pathogenic RCV000058524.2
SCN5A rs199473178 pathogenic RCV000058527.2
SCN5A rs199473179 pathogenic RCV000058529.2
SCN5A rs199473180 pathogenic RCV000058533.2
SCN5A rs199473181 pathogenic RCV000058534.2
SCN5A rs199473188 pathogenic RCV000058555.2
SCN5A rs199473194 pathogenic RCV000058565.2
SCN5A rs199473199 pathogenic RCV000058571.2
SCN5A rs199473205 pathogenic RCV000058586.2
SCN5A rs199473206 pathogenic RCV000058589.2
SCN5A rs199473207 likely pathogenic RCV000058588.2
SCN5A rs199473207 pathogenic RCV000144030.2
SCN5A rs199473208 pathogenic RCV000058591.2
SCN5A rs199473209 likely pathogenic RCV000058590.2
SCN5A rs199473210 pathogenic RCV000058592.2
SCN5A rs199473211 pathogenic RCV000058593.2
SCN5A rs199473213 pathogenic RCV000058597.2
SCN5A rs199473214 pathogenic RCV000058600.2
SCN5A rs199473217 pathogenic RCV000058609.2
SCN5A rs199473219 pathogenic RCV000058615.2
SCN5A rs199473220 pathogenic RCV000058616.2
SCN5A rs199473221 pathogenic RCV000058617.2
SCN5A rs199473225 pathogenic RCV000058623.2
SCN5A rs199473228 pathogenic RCV000058629.2
SCN5A rs199473229 pathogenic RCV000058630.2
SCN5A rs199473230 pathogenic RCV000058632.2
SCN5A rs199473231 pathogenic RCV000058633.2
SCN5A rs199473232 pathogenic RCV000058635.2
SCN5A rs199473233 pathogenic RCV000058636.2
SCN5A rs199473234 pathogenic RCV000058637.2
SCN5A rs199473235 pathogenic RCV000058638.2
SCN5A rs199473236 pathogenic RCV000058639.2
SCN5A rs199473237 pathogenic RCV000058641.2
SCN5A rs199473238 pathogenic RCV000058642.2
SCN5A rs199473239 pathogenic RCV000058646.2
SCN5A rs199473239 pathogenic RCV000058645.2
SCN5A rs199473240 pathogenic RCV000058647.2
SCN5A rs199473241 pathogenic RCV000058651.2
SCN5A rs199473242 pathogenic RCV000058652.2
SCN5A rs199473243 likely pathogenic RCV000058654.2
SCN5A rs199473244 pathogenic RCV000058655.2
SCN5A rs199473245 pathogenic RCV000058657.2
SCN5A rs199473247 pathogenic RCV000058659.2
SCN5A rs199473248 pathogenic RCV000058660.2
SCN5A rs199473249 pathogenic RCV000058661.2
SCN5A rs199473250 pathogenic RCV000058662.2
SCN5A rs199473251 pathogenic RCV000058663.2
SCN5A rs199473252 pathogenic RCV000058665.2
SCN5A rs199473254 pathogenic RCV000058669.2
SCN5A rs199473261 pathogenic RCV000058679.2
SCN5A rs199473266 pathogenic RCV000058684.2
SCN5A rs199473267 pathogenic RCV000058685.2
SCN5A rs199473269 pathogenic RCV000058691.2
SCN5A rs199473270 pathogenic RCV000058692.2
SCN5A rs199473271 pathogenic RCV000058694.2
SCN5A rs199473272 pathogenic RCV000058695.2
SCN5A rs199473273 pathogenic RCV000058697.2
SCN5A rs199473274 pathogenic RCV000058698.2
SCN5A rs199473275 pathogenic RCV000058700.2
SCN5A rs199473280 pathogenic RCV000058709.2
SCN5A rs199473281 pathogenic RCV000058713.2
SCN5A rs199473282 pathogenic RCV000009965.3
SCN5A rs199473282 pathogenic RCV000058715.2
SCN5A rs199473282 pathogenic RCV000144031.2
SCN5A rs199473284 pathogenic RCV000058720.2
SCN5A rs199473289 pathogenic RCV000058728.2
SCN5A rs199473292 pathogenic RCV000058733.2
SCN5A rs199473294 pathogenic RCV000058737.2
SCN5A rs199473295 pathogenic RCV000058738.2
SCN5A rs199473296 pathogenic RCV000058740.2
SCN5A rs199473297 pathogenic RCV000058741.2
SCN5A rs199473297 pathogenic RCV000058742.2
SCN5A rs199473298 pathogenic RCV000058744.2
SCN5A rs199473299 pathogenic RCV000058746.2
SCN5A rs199473302 pathogenic RCV000058749.2
SCN5A rs199473304 pathogenic RCV000058752.2
SCN5A rs199473305 likely pathogenic RCV000058753.2
SCN5A rs199473309 pathogenic RCV000058762.2
SCN5A rs199473313 pathogenic RCV000058769.2
SCN5A rs199473322 pathogenic RCV000058791.2
SCN5A rs199473323 pathogenic RCV000058795.2
SCN5A rs199473329 pathogenic RCV000058808.2
SCN5A rs199473332 likely pathogenic RCV000058814.2
SCN5A rs199473340 pathogenic RCV000058511.2
SCN5A rs199473550 pathogenic RCV000058625.2
SCN5A rs199473552 pathogenic RCV000058384.2
SCN5A rs199473554 pathogenic RCV000058551.2
SCN5A rs199473556 pathogenic RCV000058582.2
SCN5A rs199473557 pathogenic RCV000058640.2
SCN5A rs199473558 pathogenic RCV000058794.2
SCN5A rs199473559 pathogenic RCV000058828.2
SCN5A rs199473560 pathogenic RCV000058834.2
SCN5A rs199473561 pathogenic RCV000058837.2
SCN5A rs199473562 pathogenic RCV000058849.2
SCN5A rs199473564 pathogenic RCV000058862.2
SCN5A rs199473565 pathogenic RCV000058388.2
SCN5A rs199473566 pathogenic RCV000058394.2
SCN5A rs199473567 pathogenic RCV000058398.2
SCN5A rs199473568 pathogenic RCV000058404.2
SCN5A rs199473570 pathogenic RCV000058413.2
SCN5A rs199473573 pathogenic RCV000058434.2
SCN5A rs199473574 pathogenic RCV000058437.2
SCN5A rs199473577 pathogenic RCV000058458.2
SCN5A rs199473582 pathogenic RCV000058489.2
SCN5A rs199473586 pathogenic RCV000058510.2
SCN5A rs199473587 pathogenic RCV000058514.2
SCN5A rs199473588 pathogenic RCV000058523.2
SCN5A rs199473589 pathogenic RCV000058526.2
SCN5A rs199473592 pathogenic RCV000058546.2
SCN5A rs199473593 pathogenic RCV000058553.2
SCN5A rs199473597 pathogenic RCV000058584.2
SCN5A rs199473599 pathogenic RCV000058595.2
SCN5A rs199473601 pathogenic RCV000058603.2
SCN5A rs199473602 likely pathogenic RCV000058607.2
SCN5A rs199473605 pathogenic RCV000058628.2
SCN5A rs199473606 pathogenic RCV000058631.2
SCN5A rs199473607 pathogenic RCV000058634.2
SCN5A rs199473608 pathogenic RCV000058643.2
SCN5A rs199473609 pathogenic RCV000058648.2
SCN5A rs199473610 pathogenic RCV000058650.2
SCN5A rs199473611 pathogenic RCV000058653.2
SCN5A rs199473612 pathogenic RCV000058656.2
SCN5A rs199473613 pathogenic RCV000058664.2
SCN5A rs199473614 pathogenic RCV000058668.2
SCN5A rs199473617 pathogenic RCV000058690.2
SCN5A rs199473620 pathogenic RCV000058699.2
SCN5A rs199473621 pathogenic RCV000058702.2
SCN5A rs199473623 pathogenic RCV000058721.2
SCN5A rs199473624 pathogenic RCV000058724.2
SCN5A rs199473625 pathogenic RCV000058732.2
SCN5A rs199473626 pathogenic RCV000058736.2
SCN5A rs199473628 pathogenic RCV000058745.2
SCN5A rs199473629 pathogenic RCV000058754.2
SCN5A rs199473634 pathogenic RCV000058771.2
SCN5A rs199473636 pathogenic RCV000058793.2
SCN5A rs199473637 pathogenic RCV000058807.2
SCN5A rs201641342 likely pathogenic RCV000171573.1
SCN5A rs28937318 pathogenic RCV000009988.4
SCN5A rs28937318 pathogenic RCV000058390.2
SCN5A rs28937318 pathogenic RCV000058391.2
SCN5A rs370438420 likely pathogenic RCV000149886.1
SCN5A rs3918389 pathogenic RCV000058438.2
SCN5A rs397514252 pathogenic RCV000009966.4
SCN5A rs397514446 pathogenic RCV000009967.2
SCN5A rs397514449 pathogenic RCV000009980.4
SCN5A rs41261344 pathogenic RCV000009990.3
SCN5A rs41311087 pathogenic RCV000058779.2
SCN5A rs41313031 pathogenic RCV000010010.3
SCN5A rs45471994 pathogenic RCV000058840.2
SCN5A rs45514691 pathogenic RCV000058701.2
SCN5A rs45627438 pathogenic RCV000058431.2
SCN5A rs72549410 pathogenic RCV000197436.1
SCN5A rs727503411 likely pathogenic RCV000151808.1
SCN5A rs727504801 pathogenic RCV000156127.1
SCN5A rs727505158 pathogenic RCV000156628.1
SCN5A rs768579561 likely pathogenic RCV000155938.1
SCN5A rs794728914 pathogenic RCV000201886.1

Additional Information:

Diagnosis GeneReviews The diagnosis of Brugada syndrome is confirmed in an individual with the following:...
Clinical Description GeneReviews Brugada syndrome manifests primarily during adulthood, with a mean age of sudden death of approximately 40 years. The youngest individual diagnosed with the syndrome was two days old and the oldest age 85 years [Huang & Marcus 2004]. Although Brugada syndrome is more prevalent among males, it affects females as well, and both sexes are at a high risk for ventricular arrhythmias and sudden death [Hong et al 2004b]. ...
Genotype-Phenotype Correlations GeneReviews Few studies have investigated genotype-phenotype correlations. ...
Differential Diagnosis GeneReviews Brugada syndrome or sudden cardiac death multi-gene panels may include testing for a number of the genes associated with disorders discussed in this section. Note: The genes included and the methods used in multi-gene panels vary by laboratory and over time; a panel may not include a specific gene of interest. ...
Management GeneReviews To establish the extent of disease in an individual diagnosed with Brugada syndrome, the following evaluations are recommended:...
Molecular genetics GeneReviews Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED....