What Is Brugada Syndrome?

Updated September 23, 2019

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Brugada syndrome is a genetic cardiovascular disorder that can lead to irregular heartbeats in the lower chambers (ventricles) of the heart.

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It is classified as a rare disorder that is estimated to affect 5 in 10,000 people 1.

Spanish cardiologists Pedro Brugada and Josep Brugada first reported it as a distinct clinical syndrome in 1992.

The genetic basis of Brugada syndrome was established by Ramon Brugada in 1998 2.

Other names for this condition include:

  1. ventricular arrhythmia
  2.  idiopathic ventricular fibrillation, Brugada type
  3.  bangungut (Philippines)
  4.  non-lai tai (Laos)
  5.  lai-tai (Thailand)
  6.  pokkuri (Japan)
  7.  Pokkuri death syndrome
  8.  sudden unexpected nocturnal death syndrome
  9.  sudden unexplained death syndrome
  10.  SUDS
  11.  SUNDS

Brugada syndrome can develop at any time during a person’s life, but most commonly manifiests in adulthood.

If left untreated, the irregular heartbeats can cause fainting, difficulty breathing, seizures or even sudden death 3. These complications typically happen when a person is either resting or asleep.

It is believed that Brugada syndrome may be one of the root causes of sudden infant death syndrome (SIDS) which is a leading cause of death in infants younger than one year old.

Related to this is sudden unexplained nocturnal death syndrome (SUNDS) which takes place when unexpected cardiac arrest occurs in young adults, usually at night during sleep.

Research has concluded that SUNDS and Brugada syndrome are the same disorder.

Brugada syndrome is more prevalent in people of Asian ancestry, particularly in Japanese and Southeast Asian populations.

In addition, although it can strike both men and women, Brugada syndrome is estimated to be 8 to 10 times more common in men.

It is suspected that testosterone plays a role. They believe that this sex hormone, which is at much higher levels in men, may be linked to the higher degree of incidence.

According to the best available information, Brugada syndrome may account for 4 to 12 percent of all sudden deaths and up to 20 percent of all sudden deaths in individuals with structurally normal hearts 4.

A Quick Overview of Arrhythmias

An arrhythmia is a disorder that affects the heart rate or heart rhythm. A heart can beat irregularly, too fast (known as tachycardia), or too slow (known as bradycardia).

Normally, your heart has an electrical system that makes sure contractions take place in an orderly fashion.

These electrical impulses act as a natural pacemaker.

Different nerve messages will signal your heart to beat faster or slower. An arrhythmia is a problem with the heart’s electrical system.

Signals can be blocked, slowed or sped up. Electrical signals can sometimes also be rewired and be delivered through new and different pathways through the heart.

There are several possible causes of arrhythmia:

  • Abnormal levels of potassium or other substances in the body
  • Heart attack, or a damaged heart muscle from a past heart attack
  • Heart disease that is present at birth (congenital)
  • Heart failure or an enlarged heart
  • Overactive thyroid gland
  • Arrhythmias may also be caused by some substances or drugs, including:
  • Alcohol, caffeine, or stimulant drugs
  • Heart or blood pressure medicines
  • Cigarette smoking (nicotine)
  • Drugs that mimic the activity of your nervous system
  • Medicines used for depression or psychosis
  • Sometimes medicines used to treat one type of arrhythmia will cause another type of abnormal heart rhythm.

In addition to ventricular fibrillation, there are several other abnormal heart rhythms as well. Some of the more common ones include:

  1. Atrial fibrillation or flutter
  2.  Atrioventricular nodal reentry tachycardia (AVNRT)
  3.  Heart block or atrioventricular block
  4.  Multifocal atrial tachycardia
  5.  Paroxysmal supraventricular tachycardia
  6.  Sick sinus syndrome
  7.  Wolff-Parkinson-White syndrome

The Genetics, Causes and Risk Factors for Brugada Syndrome

Unlike other heart arrhythmias, Brugada syndrome can be caused by mutations in one of several genes.

It is inherited in an autosomal dominant pattern 5, meaning one copy of the altered gene in each cell is sufficient to cause the disorder.

In most cases, an affected person has one parent with the condition. In other instances, Brugada syndrome can result from new mutations of a gene.

This happens in cases where there is no history of the condition in an impacted person’s family.

In some cases, drugs used to treat Brugada syndrome with either increase outward currents or decrease inward currents in the heart.

This can accentuate or unmask ST-segment elevation, similar to that found in the Brugada syndrome, resulting in the production of acquired forms of the Brugada syndrome.

Drugs that can create an altered heart rhythm include medications used to treat some forms of arrhythmia, angina, high blood pressure, depression, and other mental illnesses.

Overall, more than 250 mutations associated with BrS have been reported in 18 different genes.

Despite the identification of 18 associated genes, 65% to 70% of clinically diagnosed cases remain without an identifiable genetic cause.

The most commonly mutated gene is SCN5A which is located on chromosome 3 6.

It is mutated in about 30% of affected individuals. This gene provides instructions for making a sodium channel, which normally transports positively charged sodium atoms (ions) into heart muscle cells.

An ion channel plays a critical role in maintaining the heart's normal rhythm.

Mutations in the SCN5A gene alter the structure or function of the channel. That reduces the flow of sodium ions into cells, leading to arrythmias, including Brugada syndrome.

Other genes commonly associated with Brugada syndrome include:

  • CACNA1C
  • CACNA2D1
  • CACNB2
  • GPD1L
  • HCN4
  • KCND3
  • KCNE3
  • KCNE5
  • KCNJ8
  • RANGRF
  • SCN1B
  • SCN2B
  • SCN3B
  • SLMAP
  • TRPM4

There are also a number of less common genes associated with Brugada syndrome as well. They include:

  • ABCC9
  • FGF12
  • HCN4
  • KCND2
  • KCNH2
  • PKP2
  • SCN10A
  • SEMA3A

Many of these genes are associated with making proteins that insure the right location or function of sodium channels in the heart muscle cells.

Proteins produced by other genes form or help regulate ion channels that transport calcium or potassium into or out of heart muscle cells.

The proper flow of ions through calcium and potassium channels in the heart muscle also helps maintain a regular heartbeat. Mutations in these genes also disrupt the flow of ions.

Signs and Symptoms of Brugada Syndrome

Many people may not even be aware that they have Brugada syndrome because often times, there are no noticeable symptoms.

In many cases, a diagnosis can only be confirmed by an electrocardiogram (ECG) test.

However, in other cases, there may be signs a person suffers from Brugada syndrome. Those signs and symptoms can include

  • Dizziness
  •  Fainting (syncope)
  •  Gasping, labored breathing, particularly at night
  •  Irregular heartbeats or palpitations
  •  Fast and chaotic heartbeat (sudden cardiac arrest)

Certain risk factors also increase the possibility of having Brugada syndrome. Those risk factors include:

  1. Family history of Brugada syndrome.
  2. Being male. Adult men are more frequently diagnosed than are women. In young children and adolescents, however, boys and girls are diagnosed at about the same rate.
  3. Race. Brugada syndrome occurs more frequently in Asians.
  4. Fever. A fever can irritate the heart and stimulate a Brugada-triggered faint or sudden cardiac arrest, especially in children.

Diagnosis of Brugada Syndrome

There are several methods employed in the diagnosis of Brugada syndrome.

These include a complete medical and family history that looks at any incidences of sudden cardiac death, a thorough clinical evaluation and an electrocardiogram (ECG or EKG) that records electrical activity of the heart and may reveal abnormal electrical patterns.

Doctors may use drugs known as sodium channel blockers that provoke the EKG characteristics of Brugada syndrome.

This is because your heart rhythm can change, an electrocardiogram by itself may not detect an abnormal heart rhythm.

A doctor may also give you some types of anti-anginals, antidepressants, antipsychotics or antihistamines — that can also unmask a Brugada ECG pattern. The medication is usually injected by an intravenous (IV) line.

If an ECG indicates that you have Brugada syndrome, or if you have experienced symptoms such as sudden cardiac arrest, your doctor may also recommend an Electrophysiology (EP) test in an effort to see how easy it is to get the heart to go into the abnormal Brugada rhythm.

In an EP test, a catheter is threaded through a vein in your groin to your heart, similar to cardiac catheterization.

Electrodes are then passed through the catheter to different points in your heart. The electrodes then map out any irregular heartbeats and detect electrical signals running through your heart.

Genetic testing is available for mutations in all genes to confirm the diagnosis.

The limitation here is that only about one-third of affected individuals have an identifiable gene mutation after a comprehensive genetic test.

Because it is the most commonly affected mutated gene, sequence analysis of the SCN5A gene is the first step in making a molecular genetic diagnosis.

More comprehensive genomic testing may be considered if single gene or multigene panel testing does not confirm a diagnosis in a person with symptoms of Brugada syndrome.

This testing may provide or suggest a diagnosis not previously considered, such as the mutation of a different gene or genes that results in a similar clinical presentation as Brugada syndrome.

Genetic testing has benefits as well as limitations and risks, so the decision about whether to be tested can be a personal and complex one.

A genetic counselor can help by providing information about the pros and cons of the test and discussing the medical, social and emotional aspects of testing.

If family planning is a consideration, then the time to determine if a person is at risk for Brugada syndrome is prior to pregnancy.

Genetic counseling during family planning will allow a couple to fully consider the potential risks to offspring and what the reproductive options are before moving forward.

A doctor may also recommend genetic testing to help determine whether other family members are affected if you have been diagnosed with Brugada syndrome.

It is possible that Brugada syndrome can be misdiagnosed when it is intermittent or concealed. For example, it is sometimes characterized as acute myocardial infarction

In approximately 75% of persons affected by Brugada syndrome, the diagnosis is established based on clinical history and ECG results. Genetic testing will confirm the diagnosis.

Who Should Consider Testing for Brugada Syndrome?

Brugada syndrome testing should be considered in individuals with any of the following:

  • Recurrent syncope (fainting)
  • Ventricular fibrillation
  • Self-terminating polymorphic ventricular tachycardia
  • Cardiac arrest
  • Family history of sudden cardiac death

And one of the following ECG patterns:

  • 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 (V1-V3)* (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 7.
  • 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 8
  • 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 9.

Treatments and Care Options for Brugada Syndrome Patients

The only therapy that is currently known to be effective in those with Brugada syndrome and who demonstrate syncope or cardiac arrest is through the use of Implantable cardioverter defibrillators (ICDs).

Electrical storms (multiple episodes of ventricular arrhythmias that occur over a short period of time) respond well to the introduction of isoproterenol as a first line of therapy before other antiarrhythmics are used.

In general, treatment also includes eliminating or treating 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.

Doctors will also treat patients by hospitalizing them until their ECG pattern has normalized.

Also, during and after surgery persons with Brugada syndrome should be monitored by ECG.

Quinidine has been shown to restore ST segment elevation and decrease the incidence of arrhythmias.

Hormonal changes during pregnancy can bring on arrhythmic events in women with Brugada syndrome.

Recurrent ventricular tachyarrhythmia can be inhibited following an IV infusion of low-dose isoproterenol followed by oral quinidine.

There is no consensus on treating patients who do not display any symptoms of Brugada syndrome. Some options that are employed include:

  • Observation until the first symptom develops
  • 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 benefit the most from placement of an ICD

At-risk individuals with a family history of Brugada syndrome or similar condition should undergo ECG monitoring every one to two years beginning at birth.

Genetic testing allows for the use of preventive measures and the avoidance of medications that can induce ventricular arrhythmias.

Treatments and Circumstances to Avoid

The following can unmask the Brugada syndrome ECG:

  • Febrile state
  •  Vagotonic agents
  •  α-adrenergic agonists 
  •  β-adrenergic antagonists
  •  Tricyclic antidepressants
  •  First-generation antihistamines (dimenhydrinate)
  • Cocaine toxicity

The following should be avoided:

  1. Class 1C antiarrhythmic drugs including flecainide and propafenone
  2. Class 1A agents including procainamide and disopyramide

Possible Complications and Related Diseases

Complications of Brugada syndrome require emergency medical care. They include:

Sudden cardiac arrest. If not treated immediately, this sudden loss of heart function, breathing and consciousness, which often occurs while sleeping, is fatal.

Administering cardiopulmonary resuscitation (CPR) and an external shock from an automatic external defibrillator (AED) can improve the chances of survival until emergency personnel arrive.

Fainting (syncope). If you have Brugada syndrome and you faint, seek immediate medical attention.

In cases of differential diagnosis (the process of differentiating between two or more conditions which share similar signs or symptoms), Brugada syndrome should be considered in the following circumstances:

  • 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. While rare, pathogenic variants in SCN5A gene have been previously described in a few SIDS cases.
  • Sick sinus syndrome. Brugada syndrome could be observed in persons with sick sinus syndrome given the defects observed in cardiac conduction.

Other abnormalities that can lead to ST-segment elevation and be associated with Brugada syndrome may include:

  • 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
  • Hypercalcemia
  • Hyperkalemia
  • Cocaine intoxication
  • Mediastinal tumor compressing the right ventricular outflow tract (RVOT)
  • Arrhythmogenic cardiomyopathy (AC)
  • Early repolarization syndrome
  • Other normal variants (particularly in males)

The Prognosis for Brugada Syndrome

The prognosis for people afflicted with Brugada syndrome varies widely because the condition affects each person differently.

Some cases are mild, while others are unpredictable and can cause causes a high risk of ventricular arrhythmias and sudden death.

The average age of people who pass away from sudden death due to Brugada syndrome is 40 years old 10.

People with a history of sudden cardiac arrest or fainting have an increased risk for subsequent episodes compared to people with no symptoms.

There is no cure for Brugada syndrome. In addition, no pharmacologic therapy has been proved to reduce the occurrence of ventricular arrhythmias or sudden death.

More Information if You are Living with Brugada Syndrome

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services.

Contact the following organizations and resources to see how they may be able to assist you.

Sudden Arrhythmia Death Syndromes Foundation – The SADS Foundation has a mission of saving the lives and support the families of children and adults who are genetically predisposed to sudden death due to heart rhythm abnormalities.

Arrhythmia Alliance - A-A is a coalition of charities, patient groups, patients, care givers, medical groups and allied professionals. Although these groups remain independent, they work together under the A-A umbrella to promote timely and effective diagnosis and treatment of arrhythmias.

Identification and Treatment of Sudden Death Conditions in Young Patients. A presentation by David Bradley, M.D., Director, Pediatric Heart Rhythm Service, CS Mott Children's Hospital. Assoicate Professor, Department of Pediatrics and Communicable Diseases, University of Michigan.

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.

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Referenced Sources

  1. Brugada syndrome.
    Genetics Home Reference. U.S National library of medicine. Retrieved online, August 2019.
  2. Brugada Syndrome.
    NORD - National Organization for Rare Disorders, Inc. Retrieved online, 2019.
  3. Brugada syndrome.
    National Center for Advancing Translational Sciences. Last updated: 3/16/2016.
  4. Brugada Syndrome.
    NORD - National Organization for Rare Disorders, Inc. Retrieved online, 2019.
  5. Brugada Syndrome.
    Ramon Brugada, MD, PhD, Oscar Campuzano, BSc, PhD, Georgia Sarquella-Brugada, MD, PhD, Pedro Brugada, MD, PhD, Josep Brugada, MD, PhD, and Kui Hong, MD, PhD. Initial Posting: March 31, 2005; Last Update: November 17, 2016.
  6. SCN5A gene.
    Genetics Home Reference. U.S National Library of Medicine. Retrieved online, August 2019.
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  8. Brugada Syndrome. Ramon Brugada, MD, PhD, Oscar Campuzano, BSc, PhD, Georgia Sarquella-Brugada, MD, PhD, Pedro Brugada, MD, PhD, Josep Brugada, MD, PhD, and Kui Hong, MD, PhD. Initial Posting: March 31, 2005; Last Update: November 17, 2016.
  9. Brugada Syndrome. Ramon Brugada, MD, PhD, Oscar Campuzano, BSc, PhD, Georgia Sarquella-Brugada, MD, PhD, Pedro Brugada, MD, PhD, Josep Brugada, MD, PhD, and Kui Hong, MD, PhD. Initial Posting: March 31, 2005; Last Update: November 17, 2016.
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    Genetics Home Reference. U.S National library of medicine. Retrieved online, August 2019.