Table 2. [Disorders Caused by Germline Pathogenic Variants in Brugada Syndrome-Related Genes]. - GeneReviews®

Gene	Allelic Disorder(s)
ABCC9	Cantú syndrome
Dilated cardiomyopathy
Atrial fibrillation (reported in 1 person to date [Olson et al 2007])
Early repolarization syndrome [Hu et al 2014]
CACNA1C	Long QT syndrome
Timothy syndrome (See CACNA1C-Related Disorders.)
Short QT syndrome (See CACNA1C-Related Disorders.)
CACNA2D1	Short QT syndrome [Templin et al 2011]
Early repolarization syndrome [Burashnikov et al 2010]
CACNB2	No phenotypes other than Brugada syndrome are known to be caused by germline pathogenic variants in CACNB2.
FGF12	Cerebellar atrophy w/epileptic encephalopathy (reported in 1 family to date [Siekierska et al 2016])
GPD1L	No phenotypes other than Brugada syndrome are known to be caused by germline pathogenic variants in GPD1L.
HCN4	Epilepsy [Becker et al 2017, Campostrini et al 2018]
KCND2	Epilepsy (reported in 1 person to date [Singh et al 2006])
J-wave syndromes assoc w/sudden cardiac death (reported in 1 person to date [Perrin et al 2014])
KCND3	Spinocerebellar ataxia
KCNE2	Atrial fibrillation [Yang et al 2004]
Long QT syndrome
KCNE3	No phenotypes other than Brugada syndrome are known to be caused by germline pathogenic variants in KCNE3.
KCNE5	Atrial fibrillation (reported in 1 person to date [Ravn et al 2008])
KCNH2	Long QT syndrome
Short QT syndrome [Brugada et al 2004, Grunnet et al 2008]
KCNJ8	Cantú syndrome
PKP2	Arrhythmogenic right ventricular cardiomyopathy
RANGRF	No phenotypes other than Brugada syndrome are known to be caused by germline pathogenic variants in RANGRF.
SCN1B	Temporal lobe epilepsy [Scheffer et al 2007]
Generalized epilepsy w/febrile seizures plus type 1 (GEFS+1) [Scheffer et al 2007]
Atrial fibrillation [Watanabe et al 2009]
Developmental & epileptic encephalopathy [Ramadan et al 2017]
SCN2B	Atrial fibrillation [Watanabe et al 2009]
SCN3B	Atrial fibrillation [Wang et al 2010]
SCN5A	Long QT syndrome
Progressive conduction system disease (PCCD, Lenegre disease, isolated cardiac conduction disease) [Schott et al 1999, Tan et al 2001, Wang et al 2002]
Atrial fibrillation [Olson et al 2005]
Dilated cardiomyopathy
Sick sinus syndrome [Benson et al 2003]
Familial paroxysmal ventricular fibrillation [Watanabe et al 2011]
SCN10A	Familial episodic pain syndrome [Faber et al 2012]
SEMA3A	Kallmann syndrome (See Isolated Gonadotropin-Releasing Hormone Deficiency.)
TRPM4	Erythrokeratodermia variabilis et progressiva [Wang et al 2019]
Progressive familial heart block type 1B [Kruse et al 2009]

Gene

Allelic Disorder(s)

ABCC9

Cantú syndrome

Dilated cardiomyopathy

Atrial fibrillation (reported in 1 person to date [Olson et al 2007])

Early repolarization syndrome [Hu et al 2014]

CACNA1C

Long QT syndrome

Timothy syndrome (See CACNA1C-Related Disorders.)

Short QT syndrome (See CACNA1C-Related Disorders.)

CACNA2D1

Short QT syndrome [Templin et al 2011]

Early repolarization syndrome [Burashnikov et al 2010]

CACNB2

No phenotypes other than Brugada syndrome are known to be caused by germline pathogenic variants in CACNB2.

FGF12

Cerebellar atrophy w/epileptic encephalopathy (reported in 1 family to date [Siekierska et al 2016])

GPD1L

No phenotypes other than Brugada syndrome are known to be caused by germline pathogenic variants in GPD1L.

HCN4

Epilepsy [Becker et al 2017, Campostrini et al 2018]

KCND2

Epilepsy (reported in 1 person to date [Singh et al 2006])

J-wave syndromes assoc w/sudden cardiac death (reported in 1 person to date [Perrin et al 2014])

KCND3

Spinocerebellar ataxia

KCNE2

Atrial fibrillation [Yang et al 2004]

Long QT syndrome

KCNE3

No phenotypes other than Brugada syndrome are known to be caused by germline pathogenic variants in KCNE3.

KCNE5

Atrial fibrillation (reported in 1 person to date [Ravn et al 2008])

KCNH2

Long QT syndrome

Short QT syndrome [Brugada et al 2004, Grunnet et al 2008]

KCNJ8

Cantú syndrome

PKP2

Arrhythmogenic right ventricular cardiomyopathy

RANGRF

No phenotypes other than Brugada syndrome are known to be caused by germline pathogenic variants in RANGRF.

SCN1B

Temporal lobe epilepsy [Scheffer et al 2007]

Generalized epilepsy w/febrile seizures plus type 1 (GEFS+1) [Scheffer et al 2007]

Atrial fibrillation [Watanabe et al 2009]

Developmental & epileptic encephalopathy [Ramadan et al 2017]

SCN2B

Atrial fibrillation [Watanabe et al 2009]

SCN3B

Atrial fibrillation [Wang et al 2010]

SCN5A

Long QT syndrome

Progressive conduction system disease (PCCD, Lenegre disease, isolated cardiac conduction disease) [Schott et al 1999, Tan et al 2001, Wang et al 2002]

Atrial fibrillation [Olson et al 2005]

Dilated cardiomyopathy

Sick sinus syndrome [Benson et al 2003]

Familial paroxysmal ventricular fibrillation [Watanabe et al 2011]

SCN10A

Familial episodic pain syndrome [Faber et al 2012]

SEMA3A

Kallmann syndrome (See Isolated Gonadotropin-Releasing Hormone Deficiency.)

TRPM4

Erythrokeratodermia variabilis et progressiva [Wang et al 2019]

Progressive familial heart block type 1B [Kruse et al 2009]

From: Brugada Syndrome

GeneReviews^® [Internet].

Adam MP, Feldman J, Mirzaa GM, et al., editors.

Seattle (WA): University of Washington, Seattle; 1993-2024.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright (© 1993-2024 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.