Brugada syndrome (BS) is a rare heart rhythm disorder that can predispose individuals to life-threatening arrhythmias and sudden cardiac death, often occurring during rest or sleep. This condition is primarily an electrical disease of the heart; the heart muscle itself is structurally normal in most cases. Diagnosis requires identifying a specific, characteristic pattern on an electrocardiogram (ECG), known as the Type 1 Brugada pattern, which involves an ST-segment elevation in the right precordial leads. Because BS has a strong genetic component, a diagnosis in one family member immediately raises questions about the risk to parents, siblings, and children. Understanding how this syndrome is passed down is key for families managing their collective health risk.
The Genetic Basis of Brugada Syndrome
The underlying cause of Brugada syndrome is a malfunction of the ion channels that govern the heart’s electrical activity. These channels are responsible for the controlled flow of charged particles, like sodium, into and out of heart cells, creating the electrical impulse that stimulates the heart to beat. Mutations in the genes that code for these channel proteins lead to faulty electrical signaling, a mechanism known as a channelopathy.
The most frequently identified genetic culprit is the SCN5A gene, which provides instructions for creating the primary component of the cardiac sodium channel. Mutations in SCN5A typically cause a “loss of function,” meaning the channel does not allow enough sodium current into the heart cell. This reduction in sodium current disrupts the heart’s electrical recovery phase. While SCN5A is the most common gene, it is found in only about 20–30% of clinically diagnosed cases.
Other genes have been associated with the syndrome. These include genes like SCN1B and SCN3B, which code for accessory subunits of the sodium channel, and GPD1L, which helps regulate the sodium channel’s function. The involvement of multiple genes, some of which affect sodium, calcium, or potassium channels, suggests that Brugada syndrome is not a single disease but a collection of related electrical disorders. This genetic complexity contributes to the challenges in testing and diagnosis.
Understanding the Autosomal Dominant Inheritance Pattern
Brugada syndrome is predominantly inherited in an autosomal dominant fashion. Autosomal means the gene responsible is located on one of the non-sex chromosomes. Dominant means that a person only needs to inherit one copy of the mutated gene from either parent to have the potential to develop the syndrome.
For a parent who carries a Brugada-related mutation, each of their children has a 50% chance of inheriting the altered gene. The probability of transmission is the same for male and female offspring.
The critical complexity in Brugada syndrome genetics is the concept of reduced penetrance, meaning that not everyone who inherits the genetic mutation will actually develop the characteristic ECG pattern or experience symptoms. Penetrance is estimated to be low, with studies suggesting that only a small percentage of gene carriers show the diagnostic pattern. Additionally, the syndrome exhibits variable expression, which explains why symptoms can differ widely even among family members who share the exact same mutation. This variability highlights that the risk calculation is not a simple binary outcome of having or not having the gene.
Assessing Family Risk Through Genetic Screening and Testing
Following a diagnosis in one family member, a process called cascade screening is initiated to identify other at-risk relatives. This involves systematically screening immediate family members, including parents, siblings, and children of the affected individual. The process typically combines both molecular genetic testing and clinical evaluation.
Genetic testing involves a blood test to look for the specific mutation that was identified in the first diagnosed family member. If a mutation, such as in SCN5A, is found, this test can definitively confirm whether a relative is a gene carrier. However, since a causative gene mutation is only found in a minority of clinical cases, a negative genetic test does not entirely rule out the syndrome.
Clinical screening focuses on finding the characteristic Type 1 Brugada pattern on an ECG. Since this pattern can be intermittent, a cardiologist may use a drug challenge test to “unmask” the pattern. Genetic counseling is an integral part of this process, providing families with clear information about inheritance patterns and interpreting complex test results.
Clinical Management for Asymptomatic Carriers
Asymptomatic individuals who show the diagnostic ECG pattern but have never experienced symptoms require proactive risk reduction and regular monitoring. Individuals with a drug-induced Type 1 ECG pattern are considered to have a very low annual risk of arrhythmic events, though the risk is higher for those with a spontaneous Type 1 pattern.
Regular follow-up with a heart rhythm specialist is standard practice to monitor for any changes in the ECG pattern or the development of symptoms. The most important management strategy is the rigorous avoidance of medications known to exacerbate the syndrome by further blocking the sodium channels. Families must consult a specialized list before taking any new prescription or over-the-counter drug, including certain antiarrhythmics, antidepressants, and some anesthetics.
Immediate and aggressive treatment of fever with antipyretic medications is also a priority, as fever is a well-known environmental trigger that can unmask the ECG pattern and precipitate a dangerous arrhythmia, especially in children. Avoiding excessive alcohol consumption and large meals at night can also trigger events. While an implantable cardioverter-defibrillator (ICD) is the primary treatment for high-risk symptomatic patients, it is generally avoided in asymptomatic carriers unless specific clinical risk markers are present.