Brugada syndrome

Overview

Brugada syndrome is a rare but serious inherited heart rhythm disorder that can lead to sudden cardiac arrest, particularly in otherwise healthy individuals. It is characterized by abnormal electrocardiogram (ECG) findings and an increased risk of life-threatening ventricular arrhythmias. First described in 1992 by the Brugada brothers, the syndrome is most commonly diagnosed in adults, especially males, and is a major cause of sudden cardiac death in young people, often during sleep or rest. Early detection and proper management are critical to prevent fatal outcomes.

Causes

Brugada syndrome is primarily caused by mutations in genes that control the electrical activity of the heart, especially the:

• SCN5A gene – encodes a cardiac sodium channel protein crucial for normal heart rhythm

Mutations in this gene disrupt the flow of sodium ions in heart cells, increasing the risk of abnormal rhythms. The condition is inherited in an autosomal dominant pattern, meaning a single copy of the defective gene can cause the disorder. However, not all individuals with a mutation develop symptoms, indicating variable penetrance. Other genetic mutations and unknown factors may also contribute to the syndrome.

Symptoms

Symptoms of Brugada syndrome can range from absent to severe, and often appear without warning. Common signs and symptoms include:

• Fainting (syncope) – often due to sudden arrhythmias

• Seizure-like episodes – sometimes triggered by abnormal heart rhythms

• Palpitations or irregular heartbeat

• Sudden cardiac arrest – particularly during sleep, rest, or fever

Many affected individuals remain asymptomatic until a significant or fatal event occurs, highlighting the importance of screening in at-risk families.

Diagnosis

Diagnosis of Brugada syndrome is based on ECG findings, clinical history, and genetic testing. Key diagnostic steps include:

• Electrocardiogram (ECG) – showing a characteristic “coved-type” ST-segment elevation in leads V1 to V3

• Flecainide or ajmaline challenge – a medication test used to unmask ECG abnormalities in borderline cases

• Family and personal history – including unexplained fainting, seizures, or sudden death in relatives

• Electrophysiological studies (EPS) – to assess the risk of arrhythmia induction

• Genetic testing – identifying mutations in SCN5A or other related genes

Brugada syndrome is often diagnosed incidentally during routine ECGs or evaluation following a cardiac event.

Treatment

Treatment for Brugada syndrome aims to prevent sudden cardiac death by managing arrhythmias and minimizing risk triggers. Options include:

• Implantable cardioverter-defibrillator (ICD) – the most effective treatment for patients at high risk of sudden death

• Antiarrhythmic medications – such as quinidine to reduce arrhythmic risk in selected cases

• Fever control – important in children and adults, as fever can unmask or worsen ECG abnormalities

• Avoiding certain drugs – including sodium channel blockers, some antidepressants, and anesthetics that may trigger arrhythmias.

• Lifestyle modifications – avoiding excessive alcohol, dehydration, and large meals that may provoke arrhythmias

Prognosis

The prognosis of Brugada syndrome depends on the presence of symptoms and arrhythmic risk factors. Asymptomatic individuals with a normal ECG may have a lower risk, but still require monitoring. Those with a history of fainting or sudden cardiac arrest are at significantly higher risk and benefit from ICD implantation. With appropriate treatment and lifestyle precautions, many patients with Brugada syndrome can live normal, active lives. Ongoing research into the genetics and pathophysiology of the condition may lead to improved risk stratification and therapeutic options in the future.