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Pagon RA, Bird TD, Dolan CR, et al., editors. GeneReviews [Internet]. Seattle (WA): University of Washington,
Seattle; 1993-.
Bookshelf ID: NBK1517 PMID: 20301690
Brugada Syndrome
Synonyms: Sudden Unexpected Nocturnal Death Syndrome. Includes: Brugada Syndrome 1, Brugada
Syndrome 2, Brugada Syndrome 3, Brugada Syndrome 4, Brugada Syndrome 5, Brugada Syndrome 6,
Brugada Syndrome 7, Brugada Syndrome 8
Ramon Brugada, MD, PhD
Girona Institute of Biomedical Research IDIBGI and School of Medicine
University of Girona
Girona, Spain
ramon@brugada.org
Oscar Campuzano, PhD
School of Medicine
University of Girona
Girona, Spain
oscar@brugada.org
Pedro Brugada, MD, PhD
Free University of Brussels
Brussels, Belgium
pedro@brugada.org
Josep Brugada, MD, PhD
Cardiovascular Institute
Hospital Clinic
University of Barcelona
Barcelona, Spain
josep@brugada.org
Kui Hong, MD, PhD
Heart Institute of Nanchang University
Jiangxi, China
hongkui88@163.com
Initial Posting: March 31, 2005; Last Revision: August 16, 2012.
Summary
Disease characteristics. Brugada syndrome is characterized by cardiac conduction abnormalities (ST-segment
abnormalities in leads V
1
-V
3
on ECG and a high risk for ventricular arrhythmias) that can result in sudden death.
Brugada syndrome presents primarily during adulthood; however, age at diagnosis ranges from two days to 85
years. 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 the
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.
Diagnosis/testing. Diagnosis is based on clinical findings. Mutations in eight genes (SCN5A, GPD1L,
CACNA1C, CACNB2, SCN1B, KCNE3, SCN3B, and HCN4) are known to cause Brugada syndrome. Molecular
genetic testing for all eight genes is available clinically.
Management. Treatment of manifestations: Implantable cardioverter defibrillator (ICD) in individuals with a
history of syncope or cardiac arrest; isoproterenol for electrical storms.
Prevention of primary manifestations: Quinidine (1-2 g daily). Treatment of asymptomatic individuals is
controversial.
Surveillance: ECG monitoring every one to two years for at-risk individuals with a family history of Brugada
syndrome.
Agents/circumstances to avoid: High fever, anesthetics, antidepressant drugs, and antipsychotic drugs with
sodium-blocking effects.
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Evaluation of relatives at risk: Identification of relatives at risk using ECG or (if the disease-causing mutation in
the family is known) molecular genetic testing enables use of preventive measures and avoidance of medications
that can induce ventricular arrhythmias.
Genetic counseling. Brugada syndrome is inherited in an autosomal dominant manner. Most individuals
diagnosed with Brugada syndrome have an affected parent. The proportion of cases caused by a de novo
mutation is estimated at 1%. Each child of an individual with Brugada syndrome has a 50% chance of inheriting
the mutation. Prenatal testing for pregnancies at increased risk is possible if the disease-causing mutation in the
family is known.
Diagnosis
Clinical Diagnosis
The diagnosis of Brugada syndrome is confirmed in an individual with the following:
Type 1 ECG (elevation of the J wave 2 mm with a negative T wave and ST segment that is coved type
and gradually descending) in more than one right precordial lead (V
1
-V
3
)* (see Figure 1) with or without
administration of a sodium channel blocker (i.e., flecainide, pilsicainide, ajmaline, or procainamide)

* No other factor(s) should account for the ECG abnormality.
AND
At least one of the following
Documented ventricular fibrillation
Self-terminating polymorphic ventricular tachycardia
A family history of sudden cardiac death
Coved-type ECGs in family members
Electrophysiologic inducibility
Syncope or nocturnal agonal respiration
AND/OR
Mutation in SCN5A, GPD1L, CACNA1C, CACNB2, SCN1B, KCNE3, SCN3B, or HCN4.
Brugada syndrome should be strongly considered in individuals with either of the two following ECG types:
Type 2 ECG (elevation of the J wave 2 mm with a positive or biphasic T wave; ST segment with
saddle-back configuration and elevated 1 mm) in more than one right precordial lead under baseline
conditions with conversion to type 1 ECG following challenge with a sodium channel blocker
(considered equivalent to a positive finding for At least one of the following; see above).

Note: Drug-induced ST-segment elevation to a value greater than 2 mm should raise the possibility of
Brugada syndrome when one or more of the clinical criteria are present (see At least one of the
following above). Based on current limited knowledge, whether an individual with a negative drug test
(i.e., no change observed in the ST segment in response to a sodium channel blocker) has Brugada
syndrome is unknown because the sensitivity of the test is 80% with the sodium channel blocker
ajmaline and probably lower for the other class 1 blockers [Hong et al 2004b].
Type 3 ECG (elevation of the J wave 2 mm with a positive T wave; ST segment with saddle-back
configuration and elevated <1 mm) in more than one lead under baseline conditions with conversion to
type 1 ECG following challenge with a sodium channel blocker (considered equivalent to a positive
finding for At least one of the following [above]).
Note: Drug-induced conversion of type 3 ECG to type 2 ECG is inconclusive.
See Figure 1 for a characteristic ECG observed in an individual with Brugada syndrome.
Molecular Genetic Testing
Genes. Mutations in eight genes (SCN5A, GPD1L, CACNA1C, CACNB2, SCN1B, KCNE3, SCN3B, and HCN4)
are known to cause Brugada syndrome (Table 1). See Table A for chromosome locus and protein name for these
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genes.)
Evidence for further locus heterogeneity. Because only approximately 25% of Brugada syndrome is
accounted for by mutations in the eight genes mentioned above, additional locus heterogeneity is likely. Other
genes in which mutation may cause Brugada syndrome have recently been identified; further studies must be
performed in order to clarify the associations.
KCNJ8. Previously related to early repolarization syndrome (ERS) [Haissaguerre et al 2009], KCNJ8
was implicated as a novel J-wave syndrome susceptibility gene and a marker gain of function in the
cardiac K
(ATP)
Kir6.1 channel by Valdivia et al [2010].
MOG1. MOG1 can impair the trafficking of Na
v
1.5 to the membrane, leading to I
Na
reduction and clinical
manifestation of Brugada syndrome [Kattygnarath et al 2011].
KCND3. Giudicessi et al [2011] provided the first molecular and functional evidence implicating novel
gain-of-function KCND3 mutations (Kir4.3 protein) in the pathogenesis and phenotypic expression of
Brugada syndrome, with the potential for a lethal arrhythmia being precipitated by a genetically
enhanced I
to
current gradient within the right ventricle where kcnd3 expression is the highest.
KCNE5. Although it is well established that Brugada syndrome has mainly an autosomal pattern of
inheritance, mutation of this X-linked gene has been described in one family with Brugada syndrome
[Ohno et al 2011].
Table 1. Summary of Molecular Genetic Testing Used in Brugada Syndrome
Gene Symbol /
Phenotype
Designation
% of Brugada Syndrome
Attributed to Mutations in
This Gene
Test Method Mutations Detected
Test
Availability
SCN5A / Brugada
syndrome 1
15%-30%
1
Mutation scanning /
sequence analysis
2
Sequence variants
3
Clinical
Deletion /
duplication
analysis
4
Exonic and whole-gene
deletions /
duplications
5
GPD1L / Brugada
syndrome 2
<5% Sequence analysis Sequence variants
3
Clinical
CACNA1C /
Brugada syndrome
3
<5%
Sequence analysis Sequence variants
3
Clinical
Deletion/
duplication
analysis
4
Exonic and whole-gene
deletions /
duplications
5
CACNB2 / Brugada
syndrome 4
<5% Sequence analysis Sequence variants
3
Clinical
SCN1B / Brugada
syndrome 5
<5% Sequence analysis Sequence variants
3
Clinical
KCNE3 / Brugada
syndrome 6
<5%
Sequence analysis Sequence variants
3
Clinical
Deletion /
duplication
analysis
4
Exonic and whole-gene
deletions /
duplications
5
SCN3B / Brugada
syndrome 7
<5%
Sequence analysis Sequence variants
3
Clinical
Deletion /
duplication
analysis
4
Exonic and whole-gene
deletions /
duplications
5
HCN4 / Brugada
syndrome 8
<5% Sequence analysis Sequence variants
3
Clinical
Brugada Syndrome Multi-Gene Panels
6
Clinical
Sudden Cardiac Death Multi-Gene Panels
6
Clinical
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Interpretation of test results
For issues to consider in interpretation of sequence analysis results, click here.
Testing Strategy
To confirm/establish the diagnosis in a proband. In approximately 75% of persons with Brugada syndrome
the diagnosis is established based on clinical history and ECG results. Molecular genetic testing confirms the
diagnosis and may complement clinical testing [Benito et al 2009].
Single gene testing. When molecular genetic testing is performed:
Multi-gene panel. Another strategy for molecular diagnosis of a proband suspected of having Brugada syndrome
is use of a multi-gene panel (Table 1). See Differential Diagnosis.
Predictive testing for at-risk asymptomatic adult family members requires prior identification of the disease-
causing mutations in the family.
Prenatal diagnosis and preimplantation genetic diagnosis (PGD) for at-risk pregnancies require prior
identification of the disease-causing mutations in the family.
Note: It is the policy of GeneReviews to include in GeneReviews chapters any clinical uses of testing available
from laboratories listed in the GeneTests Laboratory Directory; inclusion does not necessarily reflect the
endorsement of such uses by the author(s), editor(s), or reviewer(s).
Genetically Related (Allelic) Disorders
No other phenotypes are known to be associated with mutations in CACNB2, KCNE3, HCN4, or GPD1L.
Other phenotypes have been associated with mutations in the following genes:
Test Availability refers to availability in the GeneTests Laboratory Directory. GeneReviews designates a molecular genetic test as
clinically available only if the test is listed in the GeneTests Laboratory Directory by either a US CLIA-licensed laboratory or a non-
US clinical laboratory. GeneTests does not verify laboratory-submitted information or warrant any aspect of a laboratory's licensure
or performance. Clinicians must communicate directly with the laboratories to verify information.
1. Mutations in SCN5A have been identified in approximately 15%-30% of individuals with Brugada syndrome [Kapplinger et al 2010].
2. Sequence analysis and mutation scanning of the entire gene can have similar detection frequencies; however, detection rates for
mutation scanning may vary considerably between laboratories based on specific protocol used.
3. Examples of mutations detected by sequence analysis may include small intragenic deletions/insertions and missense, nonsense,
and splice site mutations.
4. Testing that identifies deletions/duplications not readily detectable by sequence analysis of the coding and flanking intronic
regions of genomic DNA; included in the variety of methods that may be used are: quantitative PCR, long-range PCR, multiplex
ligation-dependent probe amplification (MLPA), and chromosomal microarray (CMA) that includes this gene/chromosome segment.
See CMA.
5. No deletions or duplications involvingCACNA1C, KCNE3, or SCN3B as causative of Brugada syndrome have been reported.
(Note: By definition, deletion/duplication analysis identifies rearrangements that are not identifiable by sequence analysis of genomic
DNA.)
6. 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.
1. Sequence analysis of SCN5A is completed first as mutations in this gene are the most common cause of
Brugada syndrome.
2. If no mutation is identified, sequence analysis of CACNA1C, SCN1B, KCNE3, and SCN3B may be
considered; however, the yield is expected to be very low.
SCN5A
Long QT syndrome 3 (LQT3) (see Romano-Ward syndrome [RWS]) is characterized by QT
prolongation and T-wave abnormalities on ECG; these abnormalities are associated with
tachyarrhythmias, including the ventricular tachycardia torsade de pointes (TdP), which may cause
syncope or degenerate into ventricular fibrillation, resulting in aborted cardiac arrest (if the patient is
defibrillated) or sudden death. In several reported families, some relatives had a LQT syndrome
phenotype and others had a Brugada syndrome phenotype, supporting the concept that the two
disorders are part of a spectrum of "sodium channelopathies" [Bezzina et al 1999, Priori et al 2000b,
Veldkamp et al 2000, Grant et al 2002].
Progressive conduction system disease (PCCD, Lenegre disease, isolated cardiac conduction
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disease) manifests as slowed intramyocardial conduction and, in some cases, progressive
atrioventricular (AV) block from first-degree to complete AV block [Schott et al 1999, Tan et al 2001,
Wang et al 2002].
CACNA1C. Timothy syndrome [OMIM 601005] is a rare variant of LQTS with marked QT interval prolongation,
often presenting with 2:1 functional atrioventricular block and T wave alternans and syndactyly. It is highly
malignant, and 10/17 (59%) of the children reported [Splawski et al 2004] died at a mean age of 2.5 years. Some
children with Timothy syndrome also had congenital heart diseases, immune deficiency, intermittent
hypoglycemia, cognitive abnormalities, and autism.
SCN1B. Temporal lobe epilepsy and generalized epilepsy with febrile seizures plus type 1 (GEFS+1) [OMIM
604233] can be caused by heterozygous SCN1B mutations [Scheffer et al 2007]. In their study, Scheffer et al
[2007] found that the phenotype included: febrile seizures (FS: generalized convulsive seizures occurring with
fever between age 3 months and 6 years); febrile seizures plus (FS
+
: FS that continued after age 6 years and/or
afebrile generalized tonic-clonic seizures before age 6 years); mild generalized epilepsies and severe epileptic
encephalopathies including myoclonic-astatic epilepsy (MAE); and severe myoclonic epilepsy of infancy (SMEI).
Inheritance is autosomal dominant.
SCN3B mutations have been associated with atrial fibrillation [Wang et al 2010].
Clinical Description
Natural History
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].
Currently, the most common presentation is that of a man in his 40s with malignant arrhythmias and a previous
history of syncopal episodes. Syncope is a common presenting symptom [Mills et al 2005, Benito & Brugada
2006, Karaca & Dinckal 2006].
Males in whom sustained ventricular arrhythmias are easily induced and who have a spontaneously abnormal
ECG have a poor prognosis (i.e., a 45% likelihood of having an arrhythmic event at any time during life) [Benito et
al 2009]. Electrical storms (also known as arrhythmic storms), which are multiple episodes of ventricular
arrhythmias that occur over a short period of time, are malignant but rare phenomena in Brugada syndrome.
Incessant ventricular tachycardia (VT) is defined as hemodynamically stable VT continuing for hours.
Brugada syndrome can overlap with conduction disease. The presence of first-degree AV block, intraventricular
conduction delay, right bundle branch block, and sick sinus syndrome in Brugada syndrome is not unusual [Smits
et al 2005]. Sick sinus syndrome type 2 (SSS2) [OMIM 163800], caused by heterozygous mutations in HCN4, is
characterized by sinus node dysfunction manifest as sinus bradycardia with a tendency to develop paroxysms of
atrial fibrillation with age [Baruscotti et al 2010].
Clinical presentations of Brugada syndrome may also include sudden infant death syndrome (SIDS) (death of a
child during the first year of life without an identifiable cause) [Priori et al 2000a, Antzelevitch 2001, Skinner et al
2005, Van Norstrand et al 2007] and sudden unexpected nocturnal death syndrome (SUNDS) [Vatta et al 2002],
a syndrome seen in Southeast Asia in which young persons die from cardiac arrest with no identifiable cause.
The same mutation in SCN5A was identified in individuals with Brugada syndrome and SUNDS, thus supporting
the hypothesis that they are the same disease [Hong et al 2004a].
Precipitating factors for the Brugada ECG pattern and the syndrome of sudden cardiac death (SCD) include
fever, cocaine use, electrolyte disturbances, and use of class I antiarrhythmic medications and a number of other
non-cardiac medications [Francis & Antzelevitch 2005]. Most importantly, in some (usually young) persons, the
presence of the induced ECG pattern has been associated with sudden cardiac death. The pathophysiologic
mechanisms behind this association remain largely unknown.
Several parameters have been investigated to improve stratification of the risk of developing malignant
arrhythmias; however, data are preliminary and, thus, insufficient to develop management guidelines.
Inducibility during electrophysiologic study (EPS) is the only parameter currently used for clinical
decision making. During such a study the heart is electrically stimulated using intracardiac catheters.
Although the inducibility of arrhythmias in an asymptomatic individual during the EPS is highly predictive
of subsequent malignant events (arrhythmias and sudden cardiac death), the data remain controversial.
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Several groups do not use EPS for risk stratification in asymptomatic individuals; however, no other risk
stratification parameter is presently available [Nunn et al 2010]. Thus, decisions regarding timing of
implantation of a defibrillator vary widely among physicians and investigators [Eckardt et al 2005, Glatter
et al 2005, Ikeda et al 2005, Al-Khatib 2006, Delise et al 2006, Gehi et al 2006, Imaki et al 2006, Ito et al
2006, Ott & Marcus 2006, Tatsumi et al 2006, Benito et al 2009].
Genotype has been proposed as an additional parameter for risk stratification by Meregalli et al [2009],
who found that among individuals with an SCN5A mutation, those who were more symptomatic had
more ECG signs of conduction slowing, supporting the notion that conduction slowing, mediated by loss-
of-function SCN5A mutations, was a key pathophysiologic mechanism in Brugada syndrome. This
limited study indicates that it may be possible in the future to use genotype information in risk
stratification; however, at present this remains an area of investigation.
Pathophysiology. Brugada syndrome, caused by a sodium channelopathy, is associated with age-related
progressive conduction abnormalities, such as prolongation of the ECG PQ, QRS, and HV intervals [Smits et al
2002, Yokokawa et al 2007]. Sodium current dysfunction contributes to local conduction block in the epicardium,
resulting in multiple spikes within the QRS complex and triggering of atrial and ventricular fibrillation [Morita et al
2008].
Sodium channelopathies exhibited typical Brugada-type ECG and frequent arrhythmogenesis during bradycardia
[Makiyama et al 2005]; both quinidine and isoproterenol normalized the J-ST elevation and prevented
arrhythmias.
Genotype-Phenotype Correlations
Few studies have investigated genotype-phenotype correlations.
The degree of ST elevation and the occurrence of arrhythmias were similar between persons with
Brugada syndrome with and without an SCN5A mutation [Morita et al 2009].
In general the SCN5A mutations that cause LQT3 (see Romano-Ward syndrome) are associated with a
gain of function rather than the loss of function associated with Brugada syndrome and progressive
conduction system disease; however, mutations that are associated with both diseases in the same
family have been described.
By restoring (at least partially) sodium current defects, the common SCN5A variant p.His558Arg seems
to modulate the phenotypic effects of heterozygous SCN5A mutations [Lizotte et al 2009], such as
p.Thr512Ile which results in clinically significant cardiac conduction disturbances [Viswanathan et al
2003] and p.Arg282His which results in Brugada syndrome [Poelzing et al 2006].
Genetic variants in the SCN5A promoter region may also have a pathophysiologic role in Brugada
syndrome:
A haplotype of six normal variants has been linked to reduced expression of the sodium current
in functional studies. This haplotype, found among persons of Asian origin, could play a role in
modulating the expression of Brugada syndrome in this population [Bezzina et al 2006, Ito et al
2006].
The combination of the two Brugada syndrome mutations p.Arg1232Trp and p.Thr1620Met,
each of which produces functional but biophysically defective sodium channels by blocking
migration of the protein from nucleous to membrane, may explain disease severity [Baroudi et
al 2002, Makita et al 2008].
Brugada syndrome caused by calcium (Ca
2
) channel dysfunction does not have conduction slowing, but
does exhibit a Brugada-type ECG after administration of ajmaline [Antzelevitch et al 2007].
Penetrance
Among individuals with an SCN5A mutation:
Approximately 25% have an ECG diagnostic of Brugada syndrome;
Approximately 80% manifest the characteristic ECG changes when challenged with a sodium channel
blocker (ajmaline) [Hong et al 2004b, Benito et al 2009].
Nomenclature
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Vatta et al [2002] and Hong et al [2004a] determined that sudden unexpected nocturnal death syndrome
(SUNDS) and Brugada syndrome are phenotypically, genetically, and functionally the same disorder. SUNDS
was originally described in individuals from Southeast Asia. Other names for SUNDS include sudden and
unexpected death syndrome (SUDS), bangungut (Philippines), non-lai tai (Laos), lai-tai (Thailand), and pokkuri
(Japan).
Prevalence
Brugada syndrome was identified relatively recently; thus, it is difficult to determine its prevalence and population
distribution. Further, because the ECG is dynamic and may normalize, diagnosis may be problematic, making it
difficult to estimate the true incidence of Brugada syndrome in the general population.
Data suggest that Brugada syndrome occurs worldwide. The prevalence of the disease in endemic areas is on
the order of 1:2,000 persons. In countries in Southeast Asia in which sudden unexpected nocturnal death
syndrome (SUNDS) is endemic, it is the second cause (following accidents) of death of men under age 40 years.
Data from published studies indicate that Brugada syndrome is responsible for 4%-12% of unexpected sudden
deaths and for up to 20% of all sudden death in individuals with an apparently normal heart.
As recognition of Brugada syndrome increases in the future, a sizeable increase in the number of identified cases
can be expected.
A prospective study of an adult Japanese population (22,027 individuals) showed 12 individuals
(prevalence of 0.05%) with ECGs compatible with Brugada syndrome.
A second study of adults in Awa (Japan) showed a prevalence of 0.6% (66:10,420 individuals).
In contrast, a third study in Japanese children showed only a 0.0006% (1:163,110) prevalence of ECGs
compatible with Brugada syndrome [Hata et al 1997]. Therefore, in the absence of symptoms and/or
molecular genetic testing of SCN5A, these studies provide an estimate of the prevalence of the Brugada
syndrome ECG pattern (not of Brugada syndrome) in the population studied. The results suggest that
Brugada syndrome manifests primarily during adulthood, a finding in concordance with the mean age of
sudden death (age 35-40 years).
Differential Diagnosis
For current information on availability of genetic testing for disorders included in this section, see GeneTests
Laboratory Directory. ED.
See Table 1 for links to laboratories offering multi-gene panels that may include testing for a number of the genes
associated with disorders discussed in this section.
Other conditions that can be associated with ST-segment elevation in right precordial leads include the following
(adapted from Wilde et al [2002] with permission).
Abnormalities that can lead to ST-segment elevation in the right precordial leads
Right or left bundle-branch block, left ventricular hypertrophy
Acute myocardial ischemia or infarction
Acute myocarditis
Hypothermia, causing Osborn wave in ECGs and sometimes resembling Brugada syndrome
Right ventricular ischemia or infarction
Dissecting aortic aneurysm
Acute pulmonary thromboemboli
Various central and autonomic nervous system abnormalities
Heterocyclic antidepressant overdose
Duchenne muscular dystrophy
Friedreich ataxia
Thiamine deficiency
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Hypercalcemia
Hyperkalemia
Cocaine intoxication
Mediastinal tumor compressing the right ventricular outflow tract (RVOT)
Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C)
Other conditions that can lead to ST-segment elevation in the right precordial leads
Early repolarization syndrome
Other normal variants (particularly in males)
Most of the conditions listed can give rise to a type 1 ECG, whereas ARVD/C and Brugada syndrome can both
give rise to type 2 and type 3 ECGs. Therefore, it is important to distinguish between these two disorders.
Brugada syndrome should always be considered in the differential diagnosis of:
Sudden cardiac death and syncope in persons with a structurally normal heart
SIDS. Brugada syndrome does not usually cause problems at such a young age; however, mutations in
SCN5A have been previously described in a few SIDS cases. SIDS is believed to be etiologically and
genetically heterogeneous [Weese-Mayer et al 2007] with an unknown proportion attributed to Brugada
syndrome.
Sick sinus syndrome. Brugada syndrome could be observed in persons with sick sinus syndrome given
the defects observed in cardiac conduction [Nakazato et al 2004].
Note to clinicians: For a patient-specific simultaneous consult related to this disorder, go to
, an interactive diagnostic decision support software tool that provides differential diagnoses
based on patient findings (registration or institutional access required).
Management
Evaluations Following Initial Diagnosis
To establish the extent of disease in an individual diagnosed with Brugada syndrome, the following evaluations
are recommended:
Electrocardiogram
Induction with sodium blockers (ajmaline, procainamide, pilsicainide, flecainide) in persons with a type 2
ECG or type 3 ECG and suspicion of the disease
Electrophysiologic study to assess risk of sudden cardiac death. Although the data are controversial, no
other risk stratification parameter is presently available for asymptomatic individuals [Nunn et al 2010].
Treatment of Manifestations
Brugada syndrome is characterized by the presence of ST-segment elevation in leads V
1
to V
3
. Implantable
cardioverter defibrillators (ICDs) are the only therapy currently known to be effective in persons with Brugada
syndrome with syncope or cardiac arrest [Brugada et al 1999, Wilde et al 2002].
Electrical storms respond well to infusion of isoproterenol (1-3 g/min), the first line of therapy before other
antiarrhythmics [Maury et al 2004].
It is important to (1) eliminate/treat agents/circumstances such as fever, cocaine use, electrolyte disturbances,
and use of class I antiarrhythmic medications and other non-cardiac medications that can induce acute
arrhythmias and to (2) hospitalize the patient at least until the ECG pattern has normalized.
Controversy exists regarding the treatment of asymptomatic individuals. Recommendations vary [Benito et al
2009, Escrcega et al 2009, Nunn et al 2010] and include the following:
Observation until the first symptom develops (the first symptom can also be sudden cardiac death)
Placement of an ICD if the family history is positive for sudden cardiac death
Use of electrophysiologic study (EPS) to identify those most likely to experience arrhythmias and thus to
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benefit the most from placement of an ICD
Prevention of Primary Manifestations
Quinidine (1-2 g daily) has been shown to restore ST segment elevation and decrease the incidence of
arrhythmias [Belhassen et al 2004, Hermida et al 2004, Probst et al 2006].
Prevention of Secondary Complications
During surgery and in the postsurgical recovery period persons with Brugada syndrome should be monitored by
ECG.
Surveillance
At-risk individuals with a family history of Brugada syndrome or a known disease-causing mutation should
undergo ECG monitoring every one to two years beginning at birth [Oe et al 2005]. The presence of type I ECG
changes should be further investigated.
Agents/Circumstances to Avoid
The following can unmask the Brugada syndrome ECG [Antzelevitch et al 2002]:
Febrile state
Vagotonic agents
-adrenergic agonists [Miyazaki et al 1996]
-adrenergic antagonists
Tricyclic antidepressants
First-generation antihistamines (dimenhydrinate)
Cocaine toxicity
The following should be avoided [Antzelevitch et al 2003]:
Class 1C antiarrhythmic drugs including flecainide and propafenone
Class 1A agents including procainamide and disopyramide
Evaluation of Relatives at Risk
If the disease-causing mutation has been identified in an affected family member, molecular genetic testing of at-
risk relatives is appropriate because:
ECG changes have low sensitivity in establishing the diagnosis [Priori et al 2003];
Identification of individuals at risk allows preventive measures such as avoidance of medications that
can induce ventricular arrhythmias;
Surveillance can then be limited to family members who have the disease-causing mutation [Escrcega
et al 2009, Benito et al 2009, Nunn et al 2010].
If the disease-causing mutation has not been identified in the family, relatives should be screened with an ECG. If
a type I ECG is identified, further investigation is warranted.
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
Pregnancy Management
Hormonal changes during pregnancy can precipitate arrhythmic events in women with Brugada syndrome.
Recurrent ventricular tachyarrhythmia can be inhibited and the electrocardiographic pattern can normalize
following IV infusion of low-dose isoproterenol followed by oral quinidine [Sharif-Kazemi et al 2011].
Therapies Under Investigation
Search ClinicalTrials.gov for access to information on clinical studies for a wide range of diseases and conditions.
Note: There may not be clinical trials for this disorder.
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Registries
Contact information for voluntary patient registries is provided by GeneReviews staff.
Brugada Syndrome Registry
Web: www.brugada.org
Other
Genetics clinics, staffed by genetics professionals, provide information for individuals and families regarding the
natural history, treatment, mode of inheritance, and genetic risks to other family members as well as information
about available consumer-oriented resources. See the GeneTests Clinic Directory.
See Consumer Resources for disease-specific and/or umbrella support organizations for this disorder. These
organizations have been established for individuals and families to provide information, support, and contact with
other affected individuals.
Genetic Counseling
Genetic counseling is the process of providing individuals and families with information on the nature, inheritance,
and implications of genetic disorders to help them make informed medical and personal decisions. The following
section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic
status for family members. This section is not meant to address all personal, cultural, or ethical issues that
individuals may face or to substitute for consultation with a genetics professional. To find a genetics or prenatal
diagnosis clinic, see the GeneTests Clinic Directory.
Mode of Inheritance
Brugada syndrome is inherited in an autosomal dominant manner.
Risk to Family Members
Parents of a proband
Most individuals diagnosed with Brugada syndrome have inherited the disease-causing mutation from a
parent.
A proband with Brugada syndrome may have the disorder as the result of a de novo mutation. The
proportion of cases caused by de novo mutations is very low (~1%).
Recommendations for the evaluation of parents of a proband with an apparent de novo mutation include
electrocardiographic analysis, attention to a family history of sudden death, and (if the mutation in the
proband has been identified) molecular genetic testing.
Note: Although most individuals diagnosed with Brugada syndrome have inherited the mutation from a parent,
the family history may appear to be negative because of failure to recognize the disorder in family members,
incomplete penetrance, early death of the parent before the onset of symptoms, or late onset of the symptoms in
the affected parent.
Sibs of a proband
The risk to the sibs of the proband depends on the genetic status of the probands parents.
If a parent of the proband is affected or has a disease-causing mutation, the risk to the sibs of inheriting
the mutation is 50%.
If a disease-causing mutation cannot be detected in the DNA of either parent, two possible explanations
are germline mosaicism in a parent or a de novo mutation in the proband. To date, de novo mutations or
germline mosaicism have not been described in Brugada syndrome.
Offspring of a proband. Each child of an individual with Brugada syndrome has a 50% chance of inheriting the
mutation.
Other family members of a proband. The risk to other family members depends on the status of the probands
parents. If a parent is affected and/or has a disease-causing mutation, his or her family members are at risk.
Related Genetic Counseling Issues
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See Management, Evaluation of Relatives at Risk for information on evaluating at-risk relatives for the purpose of
early diagnosis and treatment.
Considerations in families with an apparent de novo mutation. When neither parent of a proband with an
autosomal dominant condition has the disease-causing mutation or clinical evidence of the disorder, it is likely
that the proband has a de novo mutation. However, possible non-medical explanations including alternate
paternity or maternity (e.g., with assisted reproduction) or undisclosed adoption could also be explored.
Family planning
The optimal time for determination of genetic risk and discussion of the availability of prenatal testing is
before pregnancy.
It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and
reproductive options) to young adults who are affected or at risk.
DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because
it is likely that testing methodology and our understanding of genes, mutations, and diseases will improve in the
future, consideration should be given to banking DNA of affected individuals. See for a list of
laboratories offering DNA banking.
Prenatal Testing
Prenatal diagnosis for pregnancies at increased risk is possible by analysis of DNA extracted from fetal cells
obtained by amniocentesis usually performed at approximately 15 to 18 weeks gestation or chorionic villus
sampling (CVS) at approximately ten to 12 weeks gestation. The disease-causing allele of an affected family
member must be identified before prenatal testing can be performed.
Note: Gestational age is expressed as menstrual weeks calculated either from the first day of the last normal
menstrual period or by ultrasound measurements.
Requests for prenatal testing for conditions which (like Brugada syndrome) do not affect intellect and have
treatment available are not common. Differences in perspective may exist among medical professionals and
within families regarding the use of prenatal testing, particularly if the testing is being considered for the purpose
of pregnancy termination rather than early diagnosis. Although decisions about prenatal testing are the choice of
the parents, discussion of these issues is appropriate.
Preimplantation genetic diagnosis (PGD) may be available for families in which the disease-causing mutation
has been identified. For laboratories offering PGD, see .
Note: It is the policy of GeneReviews to include in GeneReviews chapters any clinical uses of testing available
from laboratories listed in the GeneTests Laboratory Directory; inclusion does not necessarily reflect the
endorsement of such uses by the author(s), editor(s), or reviewer(s).
Molecular Genetics
Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables
may contain more recent information. ED.
Table A. Brugada Syndrome: Genes and Databases
Gene
Symbol
Chromosomal
Locus
Protein Name Locus Specific HGMD
SCN1B 19q13 .12 Sodium channel subunit beta-1 SCN1B @ LOVD SCN1B
SCN5A 3p22 .2 Sodium channel protein type 5
subunit alpha
Gene Connection for the
Heart - SCN5A (LQT3)
SCN5A @ LOVD
SCN5A @ ZAC-GGM
SCN5A
CACNA1C 12p13 .33 Voltage-dependent L-type calcium
channel subunit alpha-1C
Gene Connection for the
Heart - LQT8 (Timothy
syndrome) database
CACNA1C @ ZAC-GGM
CACNA1C @ LOVD
CACNA1C
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Table B. OMIM Entries for Brugada Syndrome (View All in OMIM)
Molecular Genetic Pathogenesis
The relationship between mutations in SCN5A and Brugada syndrome was identified in 1998. SCN5A, the gene
that encodes the subunit of the cardiac sodium channel, is responsible for the phase 0 of the cardiac action
potential. The identification of SCN5A disease-causing mutations and the decrease in availability of sodium
current suggest that a shift in the ionic balance in favor of a larger transient outward current (I
to
) during phase 1 of
the action potential causes the disease.
In addition to SCN5A alterations, mutations in SCN1B (encoding the sodium channel 1 subunit) and SCN3B
(encoding the cardiac sodium channel 3 subunit) have recently been described. The sodium current-related
genes SCN1B and SCN3B encode small subunits 1 and 3, respectively, of the Na
v
complexes. The
subunits have several functions, including interaction with ankyrin-B and -G. SCN1B encodes the 1 subunit of
the cardiac sodium channel conducting the I
Na
current. In the heart, the biophysical function of the 1 and 1b
subunits is to modify the function of Na
v
1.5 by increasing the I
Na
. SCN3B encodes the 3 subunit of the cardiac
sodium channel conducting the I
Na
current.
A second locus on chromosome 3, close to but distinct from SCN5A, has been linked to Brugada syndrome in a
KCNE3 11q13 .4 Potassium voltage-gated channel
subfamily E member 3
KCNE3 @ LOVD KCNE3
HCN4 15q24 .1 Potassium/sodium hyperpolarization-
activated cyclic nucleotide-gated
channel 4
Gene Connection for the
Heart - Sick Sinus
Syndrome database
HCN4 @ LOVD
HCN4
SCN3B 11q24 .1 Sodium channel subunit beta-3 SCN3B @ LOVD SCN3B
GPD1L 3p22 .3 Glycerol-3-phosphate
dehydrogenase 1-like protein
GPD1L @ LOVD GPD1L
CACNB2 10p12 .33-p12.31 Voltage-dependent L-type calcium
channel subunit beta-2
CACNB2 @ LOVD CACNB2
Data are compiled from the following standard references: gene symbol from HGNC; chromosomal locus, locus name, critical region,
complementation group from OMIM; protein name from UniProt. For a description of databases (Locus Specific, HGMD) to which
links are provided, click here.
114205 CALCIUM CHANNEL, VOLTAGE-DEPENDENT, L TYPE, ALPHA-1C SUBUNIT; CACNA1C
600003 CALCIUM CHANNEL, VOLTAGE-DEPENDENT, BETA-2 SUBUNIT; CACNB2
600163 SODIUM CHANNEL, VOLTAGE-GATED, TYPE V, ALPHA SUBUNIT; SCN5A
600235 SODIUM CHANNEL, VOLTAGE-GATED, TYPE I, BETA SUBUNIT; SCN1B
601144 BRUGADA SYNDROME 1; BRGDA1
604433 POTASSIUM CHANNEL, VOLTAGE-GATED, ISK-RELATED SUBFAMILY, MEMBER 3; KCNE3
605206 HYPERPOLARIZATION-ACTIVATED CYCLIC NUCLEOTIDE-GATED POTASSIUM CHANNEL 4;
HCN4
608214 SODIUM CHANNEL, VOLTAGE-GATED, TYPE III, BETA SUBUNIT; SCN3B
611777 BRUGADA SYNDROME 2; BRGDA2
611778 GLYCEROL-3-PHOSPHATE DEHYDROGENASE 1-LIKE; GPD1L
611875 BRUGADA SYNDROME 3; BRGDA3
611876 BRUGADA SYNDROME 4; BRGDA4
612838 BRUGADA SYNDROME 5; BRGDA5
613119 BRUGADA SYNDROME 6; BRGDA6
613120 BRUGADA SYNDROME 7; BRGDA7
613123 BRUGADA SYNDROME 8; BRGDA8
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large pedigree in which Brugada syndrome is associated with progressive conduction disease, a low sensitivity to
procainamide, and a relatively good prognosis. The gene was identified as GPD1L, encoding the protein glycerol-
3-phosphate dehydrogenase 1-like. This GPD1L mutation has been shown to result in a partial reduction of I
Na

caused, at least in part, by a trafficking defect.
Two other genes associated with the Brugada syndrome encode the 1 (CACNA1C) and (CACNB2b) subunits
of the L-type cardiac calcium channel. The mutations in the 1 and 2b subunits of the cardiac calcium channel
were often found to be associated with a familial sudden cardiac death (SCD) syndrome in which a Brugada
syndrome phenotype is combined with shorter than normal QT secondary to a loss of function of the calcium
channel current (I
Ca
).
The other Brugada syndrome-related gene identified is KCNE3, encoding MiRP2, a regulatory subunit of the
transient outward potassium channel I
to
, which is one of five homologous auxiliary subunits (KCNE peptides) of
voltage-gated potassium ion channels. The KCNE peptides modulate several potassium currents in the heart,
including I
Ks
(I
Kr
, and possibly I
to
).
Another gene related to Brugada syndrome is HCN4. A novel HCN4 mutation that caused abnormal splicing has
been described in a symptomatic individual. Computer simulation showed that the I
f
channel produced a
background current contributing to the action potential repolarization of ventricular cardiomyocytes. The
background current was generated by a mixed ion-selectivity for Na
+
and K
+
, and incomplete closure for the
deactivation gate of I
f
channels.
SCN5A
Normal allelic variants. The genomic sequence encompasses more than 100 kb. The gene comprises 28 exons
[Kapplinger et al 2010].
Pathologic allelic variants. More than 100 different SCN5A mutations have been reported to date [Moric et al
2003, Tan et al 2003, Kapplinger et al 2010], approximately half of which have been biophysically characterized.
Several different mutations affecting the structure, function, and trafficking of the sodium channel have been
identified.
Normal gene product. SCN5A encodes the subunit of the cardiac sodium channel gene. The protein contains
four internal repeats, each with five hydrophobic segments (S1, S2, S3, S5, S6) and one positively charged
segment (S4). S4 segments are probably the voltage sensors and are characterized by a series of positively
charged amino acids at every third position (adapted from Human Genome Browser). This integral membrane
protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or
closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-
selective channel through which Na
+
ions may pass in accordance with their electrochemical gradient. It is a
tetrodotoxin-resistant Na
+
channel isoform. The channel is responsible for the initial upstroke of the action
potential in the ECG. The protein is expressed in human atrial and ventricular cardiac muscle but not in adult
skeletal muscle, brain, myometrium, liver, or spleen.
Abnormal gene product. The common feature is the decrease in Na
+
current availability by two main
mechanisms: lack of expression of the mutant channel or accelerated inactivation of the channel [Benito et al
2009].
GPD1L
Normal allelic variants. The gene comprises eight exons.
Pathologic allelic variants. In 2007, the mutation p.Ala280Val and the novel SIDS-associated mutation
p.Glu83Lys were both shown to decrease cardiac I
Na
amplitude. The mutation p.Ala280Val reduces inward
sodium currents by approximately 50% and SCN5A cell surface by approximately 31% [London et al 2007, Van
Norstrand et al 2007].
Normal gene product. The genomic sequence encodes 351 amino acids. The protein glycerol 3-phosphate
dehydrogenase 1-like (G3PD1L) affects the trafficking of the cardiac Na
+
channel to the cell surface.

CACNA1C
Normal allelic variants. The gene comprises 47 exons.
Pathologic allelic variants. The association between CACNA1C and Brugada syndrome was established by the
finding of two missense mutations in CACNA1C (p.Ala39Val, p.Gly490Arg).
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Normal gene product. The genomic sequence encodes a protein of 2221 amino acids. CACNA1C encodes a
number of isoforms of the pore-forming 1 subunit of the long-lasting (L-type) voltage-gated calcium channel
(Ca
v
1.2). The Ca
v
1.2 channel is activated upon depolarization of the cardiomyocyte, and is responsible for the
depolarizing influx of calcium, the L-type calcium current (I
CaL
). I
CaL
inactivates very slowly; thus, it is of major
significance for maintaining the plateau phase of the AP. Furthermore, it is the most important source of
intracellular calcium and it represents the coupling between excitation and contraction by inducing release of
calcium from the sarcoplasmic reticulum through calcium activation of the Ryanodine receptors.
Abnormal gene product. When expressed with other Ca
v
1.2 subunits in CHO cells, a clearly reduced I
CaL
was
found in both cases. Thus, the mechanism of Brugada syndrome with these mutations (i.e., decreased
depolarizing current during AP) was independent of SCN5A [Antzelevitch et al 2007].
CACNB2
Normal allelic variants. The gene comprises 14 exons.
Pathologic allelic variants. The missense mutation p.Ser481Leu is located in the C-terminal part of Ca
v2
close
to the Ca
v
1.2 binding domain.
Normal gene product. The genomic sequence encodes a protein of 660 amino acids. CACNB2 encodes the 2
subunit (Ca
v2
) of Ca
v
1.2, which modifies gating (increasing the I
CaL
) and has been associated with Brugada
syndrome 4. Ca
v2
functions as a chaperone for the subunit of Ca
v
1.2, ensuring its transport to the plasma
membrane. It is the dominantly expressed Ca
v
1.2 subunit in the heart.
Abnormal gene product. Because the mutation is located in close proximity to the DIDII linker of Ca
v
1.2,
interference with the stimulatory role of Ca
v2
on I
Ca
is a likely pathogenic mechanism for this mutation. The
mechanism of Brugada syndrome 4 involves a reduction of the depolarizing I
Ca
[Cordeiro et al 2009].
SCN1B
Normal allelic variants. The gene comprises three exons.
Pathologic allelic variants. Three mutations in SCN1B have been identified segregating with arrhythmia.
SCN1B transcripts were expressed in the human heart and were abundant in Purkinje fibers that play a critical
role in electric pulse conduction in heart.
Normal gene product. The genomic sequence encodes a protein of 218 amino acids. SCN1B encodes the 1
subunit of the cardiac sodium channel conducting the I
Na
current. In the heart the biophysical function of the 1
subunits and 1b splicing variant is to modify the function of Na
v
1.5, by increasing the I
Na
(+69% and +76%,
respectively).
Abnormal gene product. Electrophysiologic study of heterologously expressed sodium channels revealed loss
of sodium current with mutant subunits [Watanabe et al 2008].
KCNE3
Normal allelic variants. The gene comprises two exons.
Pathologic allelic variants. The relation between mutations in KCNE3 and Brugada syndrome 6 was
established in a Danish family with four individuals who had a type 1 Brugada syndrome ECG pattern and normal
QT-interval and the heterozygous KCNE3 missense mutation p.Arg99His. When the mutated KCNE3 was
coexpressed in CHO cells with K
v
4.3 (the subunit of the I
to
channel), an increase in the I
to
as well as an
accelerated inactivation of the current were observed [Delpn et al 2008].
Normal gene product. The genomic sequence encodes a protein of 103 amino acids. KCNE3 encodes MiRP2,
one of five homologous auxiliary subunits (KCNE peptides) of voltage-gated potassium ion channels. The
KCNE peptides modulate several potassium currents in the heart, including I
Ks
, I
Kr
, and I
to
.
Abnormal gene product. See Pathologic allelic variants.
SCN3B
Normal allelic variants. The gene comprises five exons.
Pathologic allelic variants. A mutation in SCN3B was found associated with Brugada syndrome.
Normal gene product. The genomic sequence encodes a protein of 215 amino acids. SCN3B encodes the 3
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subunit of the cardiac sodium channel conducting the I
Na
current. In the heart the function of the 3 subunit is to
modify the function of Na
v
1.5 by increasing the I
Na
as for the 1 subunit, albeit with another kinetics.
Abnormal gene product. When the mutation p.Leu10Pro was expressed in TSA201 cells together with SCN5A
and SCN1B, the mutation was found to result in defective trafficking of Na
v
1.5 and reduced I
Na
[Hu et al 2009].
HCN4
Normal allelic variants. The gene comprises eight exons.
Pathologic allelic variants. An HCN4 mutation that caused abnormal splicing was identified in a symptomatic
individual with Brugada syndrome. HCN4 mutations affect channel properties even in the absence of overt
clinical findings [Ueda et al 2009].
Normal gene product. The HCN4 genomic sequence encodes a protein of 1203 amino acids.
Resources
See Consumer Resources for disease-specific and/or umbrella support organizations for this disorder. These
organizations have been established for individuals and families to provide information, support, and contact with
other affected individuals. GeneTests provides information about selected organizations and resources for the
benefit of the reader; GeneTests is not responsible for information provided by other organizations.ED.
References
Medical Genetic Searches: A specialized PubMed search designed for clinicians that is located on the PubMed
Clinical Queries page
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Suggested Reading
1. Antzelevitch C, Brugada P, Borggrefe M, Brugada J, Brugada R, Corrado D, Gussak I, LeMarec H,
Nademanee K, Perez Riera AR, Shimizu W, Schulze-Bahr E, Tan H, Wilde A. Brugada syndrome:
report of the second consensus conference. Heart Rhythm. 2005;2:42940. [PubMed: 15898165]
2. Brugada P, Brugada R, Brugada J. Should patients with an asymptomatic Brugada electrocardiogram
undergo pharmacological and electrophysiological testing? Circulation. 2005;112:27992. [PubMed:
16009809]
3. Brugada R, Brugada P, Brugada J. Electrocardiogram interpretation and class I blocker challenge in
Brugada syndrome. J Electrocardiol. 2006;39:S1158. [PubMed: 16934827]
4. Keating MT, Sanguinetti MC. Familial cardiac arrhythmias. In: Scriver CR, Beaudet AL, Sly WS, Valle D,
Vogelstein B, eds, The Metabolic and Molecular Bases of Inherited Disease (OMMBID). New York, NY:
McGraw-Hill. Chap 203. Available at www .ommbid.com. Accessed 8-14-12.
5. Morita H, Zipes DP, Morita ST, Wu J. Genotype-phenotype correlation in tissue models of Brugada
syndrome simulating patients with sodium and calcium channelopathies. Heart Rhythm. 2010;7:8207.
[PubMed: 20206324]
6. Morita H, Nagase S, Miura D, Miura A, Hiramatsu S, Tada T, Murakami M, Nishii N, Nakamura K, Morita
ST, Oka T, Kusano KF, Ohe T. Differential effects of cardiac sodium channel mutations on initiation of
ventricular arrhythmias in patients with Brugada syndrome. Heart Rhythm. 2009;6:48792. [PubMed:
19324308]
7. Morita H, Zipes DP, Morita ST, Lopshire JC, Wu J. Epicardial ablation eliminates ventricular arrhythmias
in an experimental model of Brugada syndrome. Heart Rhythm. 2009;6:66571. [PubMed: 19328041]
Chapter Notes
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Author Notes
Ramon Brugada, MD is Dean of the School of Medicine of the University of Girona (Spain), Director of the
Cardiovascular Genetics Center at the Biomedical Institute of Girona, and cardiologist at the Hospital Trueta in
Girona.
Clinical interest. As a clinical and noninvasive cardiologist, Dr. Brugada is interested in the
management of patients with inherited disorders of the heart.
Research interest. Dr. Brugada's research interests are focused on molecular genetics of
cardiovascular disease with an emphasis on genetics of cardiac arrhythmias. His research
achievements include the identification of the chromosomal locus on 10q22 for familial atrial fibrillation,
the gene for familial idiopathic ventricular fibrillation (Brugada syndrome), and the gene for short QT
syndrome.
Revision History
16 August 2012 (cd) Revision: multi-gene panels for Brugada syndrome and sudden cardiac death
available clinically
12 January 2012 (cd) Revision: clinical testing for mutations in CACNB2 and HCN4 now listed in the
GeneTests Laboratory Directory; large deletion in SCN5A reported [Eastaugh et al 2011]
8 September 2011 (me) Comprehensive update posted live
11 August 2009 (cd) Revision: prenatal testing for SCN5A available clinically
7 December 2007 (me) Comprehensive update posted to live Web site
31 March 2005 (me) Review posted to live Web site
11 March 2004 (rb) Original submission
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Figures
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Figure 1. Characteristic ECG in Brugada syndrome. Note presence of ST-segment elevation in leads V
1
-V
3
,
coved type.
Copyright 1993-2012, University of Washington, Seattle. All rights reserved.
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