Brugada Syndrome

Brugada Syndrome

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Brugada Syndrome is not the name you expected.

Disorder Subdivisions

  • None

General Discussion

Summary

Brugada syndrome is a rare inherited cardiovascular disorder characterized by disturbances affecting the electrical system of the heart. The main symptom is irregular heartbeats and, without treatment, may potentially result in sudden death. In some cases, no symptoms may precede sudden death. Brugada Syndrome typically begins onset in adulthood and follows autosomal dominant inheritance. The prevalence rate of the disease is currently unknown due to its recent identification.



Introduction

The normal heart has four chambers. The two upper chambers are known as the atria and the two lower chambers are known as the ventricles. Electrical impulses cause the heart to beat. In individuals with Brugada syndrome, the electrical impulses between the ventricles become uncoordinated (ventricular fibrillation) resulting in decreased blood flow. Decreased blood flow to the brain and heart may result in fainting or sudden death.

Brugada syndrome is named by the Spanish cardiologists Pedro Brugada and Josep Brugada who reported it as a distinct clinical syndrome in 1992.

Symptoms

An affected individual with Brugada syndrome typically begins to show symptoms around the age of 40. Individuals with Brugada syndrome may experience irregular heartbeats (ventricular arrhythmias) or may have no apparent symptoms (asymptomatic). Irregular heartbeats may cause difficulty breathing, loss of consciousness or fainting (syncope), and sudden death.



The severity of symptoms varies from case to case. There are some known triggers for Brugada syndrome, like fever and sodium blocking drugs.



A specific presentation of Brugada syndrome is known as sudden unexpected nocturnal death syndrome (SUNDS). SUNDS is prevalent is Southeast Asia and occurs in young individuals, who die from cardiac arrest during sleep with no apparent or identifiable cause. Another presentation of Brugada syndrome is sudden infant death syndrome (SIDS), which is the death of a child within the first year of life without an identifiable cause.

Causes

Brugada Syndrome is caused mainly by a sodium channelopathy (mutations in SCN5A), which is a disturbed functioning of sodium channel subunits or proteins that regulate them. Dysfunction of the sodium channels leads to local conduction blockages in the heart.



Mutations in other genes (GPD1L, CACNA1C, CACNB2, SCN1B, KCNE3, SCN3B, and HCN4) are also known to cause Brugada syndrome. These mutations are inherited in an autosomal dominant manner from parents to their children. This means only a single copy of an abnormal gene is necessary for the appearance of the disease in an individual. Most individuals with the disease also have an affected parent. Each child of an affected individual has a 50% chance of inheriting the genetic variation, regardless of the sex of the individual.



The primary gene known to be associated with Brugada syndrome is located on chromosome 3 and has been termed the SCN5A gene. Approximately 15-30% of individuals with Brugada syndrome have a SCN5A gene mutation. This gene is responsible for the production of a protein that allows movement of sodium atoms into heart muscle cells through a channel called the sodium channel. Abnormalities in the SCN5A gene change the structure or function of the sodium channel and result in a reduction of sodium into the heart cells. Reduced sodium can lead to an abnormal heart rhythm that can lead to sudden death. SCN5A gene mutations are also associated with the long QT syndrome type 3 (LQT3), which is one form of a heart rhythm abnormality called Romano-Ward syndrome. Some families have been reported that have relatives with Brugada syndrome and LQT3, suggesting that these conditions may be different types of the same disorder.

Affected Populations

Brugada syndrome affects both men and women, but occurs more often in men. The incidence rate is currently unknown due to its recent identification and discovery. It is estimated to affect 5 out of every 10,000 people. Brugada syndrome occurs worldwide, but is seen more frequently in individuals of Southeast Asia and Japan. According to the medical literature, Brugada syndrome may account for 4 to 12 percent of all sudden deaths and 20 percent of all sudden deaths in individuals with structurally normal hearts.



Brugada syndrome may affect individuals of any age, but symptoms most often occur in middle-aged men around the age of 40. The disorder was first described in the medical literature in 1992.

Standard Therapies

Diagnosis

The diagnosis of Brugada syndrome is based on a thorough clinical evaluation, a complete medical and family history that may include a family history of sudden cardiac death, and a specialized test known as an electrocardiogram (ECG of EKG) that records electrical activity of the heart and may reveal abnormal electrical patterns. Physicians may use specific drugs (sodium channel blockers) that provoke characteristic EKG features of Brugada syndrome.



Molecular genetic (DNA) testing is available for mutations in all eight genes to confirm the diagnosis but only about 20-25% of affected individuals have an identifiable gene mutation. Sequence analysis of the SCN5A gene is the first step in making a molecular genetic diagnosis because mutations in this gene are the most common cause of Brugada syndrome.



Clinical Testing and Work-Up

An electrocardiogram is recommended to determine the extent of disease in those affected. An electrophysiologic study may be used to assess risk of sudden cardiac death.



Treatment

No cure for Brugada syndrome exists. Individuals at a high risk of ventricular fibrillation are treated with an implantable cardioverter defibrillator (ICD). This device detects the abnormal heartbeat automatically and selectively delivers an electrical impulse to the heart restoring normally rhythm.



Isoproterenol is an antiarrhythmic, which is used an effective way to respond to electrical storms (unstable ventricular arrhythmias). Recommendations for treatment of asymptomatic individuals is controversial. Possible treatments may include: observation until symptoms develop, although the first symptom is sometimes sudden cardiac death, or the use of family history or electrophysiologic study to determine who is appropriate for ICD placement.



Genetic counseling is recommended for affected individuals and their families. Other treatment is symptomatic and supportive.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.



For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:



Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com



For information about clinical trials conducted in Europe, contact:

https://www.clinicaltrialsregister.eu/

References

TEXTBOOK

Towbin JA. Brugada Syndrome. In: NORD Guide to Rare Disorders. Philadelphia, PA: Lippincott Williams & Wilkins. 2003:45.



JOURNAL ARTICLES

Shimizu W, Aiba T, Antzelevitch C. Specific therapy based on the genotype and cellular mechanism in inherited cardiac arrhythmias. Long QT syndrome and Brugada syndrome. Curr Pharm Des. 2005;11:1561-72.



Satish OS, Yek KH, Wen MS. Brugada syndrome-an update. Chang Gun Med J. 2005;28:69-76.



Brugada P, Brudaga R, Antzelevitch C, Brugada J. The Brugada Syndrome. Arch Mal Coeur Vaiss. 2005;98:115-22.



Sreeram N, Simmers T, Brockmeier K. The Brugada syndrome. It's relevance to paediatric patients. Z Kardiol. 2004;93:784-90.



Antzelevitch C. Brugada syndrome: clinical, genetic, molecular, cellular and ionic aspects. Expert Rev Cardiovasc Ther. 2003;1:177-85.



Antzelevitch C, Brugada P, Brugada J, Brugada R, Towbin JA, Nademanee K. Brugada syndrome: 1992-2002: a historical perspective. J Am Coll Cardiol. 2003;41:1665-71.



Antzelevitch C, Brugada P, Brugada J, et al., Brugada syndrome: a decade of progress. Circ Res. 2002;91:1114-8.



Brugada P, Brugada R, Brugada J. The Brugada syndrome. Curr Cardio Rep. 2000;2:507-14.



Brugada P, Brugada J. Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome: a multicenter report. J Am Coll Cardiol. 1992;20:1391-6.



INTERNET

Brugada R, Campuzano O, Brugada P, Brugada J, Hong K. (Updated:August 16, 2012). Brugada Syndrome. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2013. Available at http://www.genetests.org. Accessed:February 5, 2013.



Dizon JM, Nazif TM.Brugada Syndrome. Emedicine. http://emedicine.medscape.com/article/163751-overview. Updated June 5, 2012. Accessed:February 5, 2013.



Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Brugada Syndrome 1; BRGDA1. Entry No: 601144. Last Edited December 20, 2011. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed:February 5, 2013.

Resources

American Heart Association

7272 Greenville Avenue

Dallas, TX 75231

Tel: (214)784-7212

Fax: (214)784-1307

Tel: (800)242-8721

Email: Review.personal.info@heart.org

Internet: http://www.heart.org



Sudden Arrhythmia Death Syndromes Foundation

508 E. South Temple

Suite 202

Salt Lake City, UT 84102

USA

Tel: (801)531-0937

Fax: (801)531-0945

Tel: (800)786-7723

Email: laura@sads.org

Internet: http://www.sads.org



Cardiac Arrhythmias Research and Education Foundation, Inc. (C.A.R.E)

427 Fulton Street

P.O. Box 69

Seymour, WI 54165

USA

Fax: (920)833-7005

Tel: (800)404-9500

Email: care@careforhearts.org

Internet: http://www.longqt.org or http://www.careforhearts.org



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



Ramon Brugada Senior Foundation

Pic de Peguera 15

Girona, 17003

Spain

Tel: 34 972 183366

Fax: 34 972 183367

Email: ramon@brugada.org

Internet: http://www.brugada.org/foundation/foundation.html



For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.

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