Brugada syndrome

The genetic form of Brugada syndrome (not the acquired form) is inherited in an autosomal dominant manner. This means that having one mutated copy of the responsible gene in each cell is enough to cause signs or symptoms. Almost all people with Brugada syndrome have a parent with the condition. In about 1% of cases, an affected person has a new mutation in the responsible gene and has no family history of the condition. Each child of an affected person has a 50% chance to inherit the mutated gene.

Unsymptomatic parents of an affected person should be evaluated with electrocardiography, and any family history of sudden death should be discussed. If genetic testing reveals a mutation in the affected person, genetic testing of the parents is recommended. A family history may appear to be negative due to reduced penetrance, death of a parent before symptoms start, or late onset of symptoms in an affected parent.

In almost all cases, a person with Brugada syndrome inherits the condition from a parent who has a mutated copy of one of the genes responsible for the condition. In about 1% of cases, the condition results from a new ( de novo ) mutation that occurs for the first time in the affected individual.

Mutations that cause Brugada syndrome have been found in 16 different genes. However, only about 25% to 30% of cases are caused by a mutation in one of these genes (usually the SCN5A gene). This means that there are likely mutations in other, unidentified genes that cause Brugada syndrome. This also means that 70-75% of affected people will not test positive for a mutation when they have genetic testing.

If a genetic mutation is found in an affected family member, genetic testing of both parents and other at-risk relatives is appropriate. Genetic testing only in the affected person does not show where the mutation came from.

If a mutation in an affected person is not found, relatives should be screened with an ECG, and further testing may be needed in some cases. Attention to a family history of sudden death can be important in determining who may be at risk for the condition.

People interested in learning more about the inheritance of Brugada syndrome and genetic testing should speak with a genetics professional.

We are unable to give medical advice or recommendations for management or lifestyle choices. The risk of complications and/or sudden death can differ among affected people, and recommendations for particular athletes may differ based on several factors. The type and level of activity deemed safe for one person may not be deemed safe for another. People with Brugada syndrome (or a family history) should discuss their questions about physical activity with their electrophysiologist or cardiologist for guidance.

The literature on sudden cardiac death (SCD) during exertion has mainly focused on competitive sports. However, recreational activity limitations are also important in people with any heart disease that is commonly associated with SCD. At least some level of activity restriction is recommended for nearly all people with underlying heart disease. There is also limited information regarding the best course of management for children with Brugada syndrome.

According to a statement published in 2015 by the American Heart Association and the American College of Cardiology (for competitive athletes):

• For athletes with a suspected or diagnosed cardiac channelopathy (syndrome that affects the heart's electrical system), a comprehensive evaluation by a heart rhythm specialist (electrophysiologist) or genetic cardiologist with sufficient experience and expertise with these disorders is recommended.
• It is recommended that symptomatic athletes with any suspected or diagnosed cardiac channelopathy be restricted from all competitive sports until a comprehensive evaluation has been completed, the athlete and his or her family are well informed, a treatment program has been implemented, and the athlete has been asymptomatic on therapy for 3 months.
• It is reasonable for an affected athlete with no signs and symptoms (with an identified genetic mutation) to participate in all competitive sports with appropriate precautionary measures, such as:
  • the avoidance of drugs that exacerbate Brugada syndrome;
  • avoidance of dehydration, hyperthermia (high body temperature), heat exhaustion, and heat stroke;
  • obtaining a personal, automatic, external defibrillator; and
  • establishing an emergency plan with school or team officials.
• In an athlete with previous symptoms, or findings of Brugada syndrome on electrocardiography, participation in competitive sports may be considered if:
  • precautionary measures are taken, and
  • disease-specific treatments are in place, and
  • the athlete has been asymptomatic on therapy for at least 3 months.

Previous guidelines appear to have been more restrictive. For example, for competitive athletes, the 2005 36th Bethesda Conference recommended the following approach for an athlete with Brugada syndrome:

• Although a clear association between exercise and sudden death has not been established, because of the potential impact of hyperthermia (high body temperature) and enhanced parasympathetic activity (part of the nervous system that conserves energy and slows the heart rate) induced by athletic training, restriction to participation in low-intensity sports seems advisable.

For recreational athletes, the 2004 American Heart Association scientific statement recommended that people with Brugada syndrome should avoid or participate cautiously in most high-intensity noncompetitive sports, including basketball, ice hockey, sprinting, and singles tennis.

Sports that cause significant risk of impaired consciousness may not be advised for people with Brugada syndrome.

Again, people with questions about the type and level of physical activity that is safe for themselves or family members are strongly encouraged to speak with their physician.

The long-term outlook (prognosis) for people with Brugada syndrome varies because the condition is very unpredictable. The condition manifests primarily during adulthood, and causes a high risk of ventricular arrhythmias and sudden death. The average age of sudden death is approximately 40 years. Affected people with a history of sudden cardiac arrest and/or fainting have an increased risk for subsequent episodes compared to people with no symptoms.