• SCN5A
• Ancestry
• Channelopathies
• Ecuador
• Genomic

• Humans
• Female
• NAV1.5 Voltage-Gated Sodium Channel/genetics
• Ecuador
• Phenotype
• Genetic Predisposition to Disease
• Adolescent
• Atrial Flutter/genetics
• Atrial Flutter/diagnosis
• Atrial Flutter/physiopathology
• Mutation
• Pedigree

• Adult
• Brugada Syndrome/complications
• Brugada Syndrome/genetics
• Brugada Syndrome/physiopathology
• Death, Sudden, Cardiac/epidemiology
• Death, Sudden, Cardiac/etiology
• Electrocardiography
• Female
• Humans
• Long QT Syndrome/epidemiology
• Long QT Syndrome/etiology
• Male
• Middle Aged
• Mutation
• NAV1.5 Voltage-Gated Sodium Channel/genetics
• Registries
• Risk Assessment
• Sex Distribution
• Sex Factors
• Syncope/epidemiology
• Syncope/etiology
• Taiwan/epidemiology

• Brugada syndrome
• overlap syndrome
• sick sinus syndrome
• sinus node dysfunction
• sodium channel mutation

In 1992, the Brugada syndrome (BrS) was recognized as a disease responsible for sudden cardiac death, characterized by a right bundle-branch block with ST segment elevation in the leads V1 and V2. This syndrome is highly associated with sudden cardiac death, especially in young males. BrS is currently diagnosed in patients with ST-segment elevation showing type 1 morphology ≥ 2 mm in ≥1 leads among the right precordial leads V1 or V2 positioned in the 2nd, 3rd, or 4th intercostal space, and occurring either spontaneously or after a provocative drug test by the intravenous administration of Class I antiarrhythmic drugs. With accumulated findings, the BrS inheritance model is believed to be an autosomal dominant inheritable model with incomplete penetrance, although most patients with BrS were sporadic cases. SCN5A, which was identified as the first BrS-associated gene in 1998, has emerged as the most common gene associated with BrS, and more than 10 BrS-associated genes have been identified thereafter. Mutation-specific genetic testing is recommended for the family members and appropriate relatives following the identification of BrS-causative mutations in an index patient. In addition, comprehensive or BrS1 (SCN5A) targeted genetic testing could be useful for patients in whom a cardiologist has established a clinical index of suspicion for BrS based on the patient׳s clinical history, family history, and the expressed electrocardiographic (resting 12-lead ECGs and/or provocative drug challenge testing) phenotype.

Over the past 20 years, extensive research in this field has allowed better understanding of the pathophysiology, genetic background, and management of BrS even though controversies still exist. In this review article, a background of genetics, the genetic background of BrS, the genotype and phenotype relationship, the role of genetic screening in clinical practice, and the interpretation of the identified genetic variants have been addressed based on this understanding.

• Brugada syndrome
• Genetics

• Adult
• Aged
• Brugada Syndrome/diagnosis
• Brugada Syndrome/genetics
• Brugada Syndrome/metabolism
• Brugada Syndrome/pathology
• Child
• Death, Sudden, Cardiac
• Electrocardiography
• Female
• Genetic Testing
• Humans
• Male
• Middle Aged
• Pregnancy
• Sodium Channels/metabolism

Brugada syndrome (BrS) is a rare and inherited primary arrhythmic syndrome characterized by ST-segment elevations in the right precordial leads (V₁-V₃) with an increased risk of sudden cardiac death (SCD). Arrhythmias in BrS are often nocturne, and brady-arrhythmias are often seen in patients with loss-of-function mutations in SCN5A. In this case-report we present a 75-year old woman referred to our outpatient clinic for inherited cardiac diseases for a familial clinical work-up. Since childhood she had suffered from dizziness, absence seizures, and countless Syncope’s. In 2004 sick sinus syndrome was suspected and she was treated with implantation of a pacemaker (PM) at another institution. An inherited cardiac disease was one day suddenly suspected, as the patient had a 61-year old brother who was diagnosed with symptomatic BrS, and treated with an implantable cardioverter defibrillator (ICD) after aborted SCD. A mutation screening revealed a SCN5A [S231CfsX251 (c.692-693delCA)] loss-of-function mutation not previously reported, and as a part of the cascade screening in relatives she was therefore referred to our clinic. In the 7 year period after PM implantation she had experienced no cardiac symptoms, although her electrocardiogram changes now were consistent with a BrS type 1 pattern. A genetic test confirmed that she had the same mutation in SCN5A as her brother. In this case-report we present a loss-of function mutation in SCN5A not previously associated with BrS nor presented in healthy controls. Sinus node dysfunction has previously been documented in patients with symptomatic BrS, which suggests it is not a rare concomitant. The only accepted treatment of BrS is today implantation of an ICD. In the future studies should evaluate if PM in some cases of symptomatic BrS can be used instead of ICDs in patients with a loss-of-function SCN5A mutations

• Brugada syndrome
• Pacemaker
• Arrhythmias
• Sudden cardiac death