Brugada Syndrome

Cardiology section

Brugada syndrome disrupts the heart's normal rhythm, specifically causing irregular heartbeats in the lower chambers (ventricles), known as ventricular arrhythmia. Untreated, these irregular heartbeats can result in fainting (syncope), seizures, difficulty breathing, or sudden death. Typically, these complications occur during rest or sleep. While Brugada syndrome typically manifests in adulthood, it can develop at any stage of life, and symptoms related to arrhythmias, including sudden death, can occur from early infancy to late adulthood. Sudden death tends to occur

around age 40. Notably, Brugada syndrome may elucidate some cases of sudden infant death syndrome (SIDS), a significant cause of death in infants under one year, characterized by unexplained and abrupt death, often during sleep. Sudden Unexplained Nocturnal Death Syndrome (SUNDS) is a condition marked by unexpected cardiac arrest in young adults, typically during nighttime sleep. Originally identified in Southeast Asian populations as a major cause of death, researchers have established that SUNDS and Brugada syndrome are the same disorder.

ABOUT BRUGADA SYNDROME

UNDERSTANDING brugada syndrome

Insights into Brugada Syndrome

Brugada syndrome is primarily associated with genetic mutations affecting ion channels in the heart, which can lead to abnormal electrical activity and an increased risk of dangerous arrhythmias.

The most common gene associated with Brugada syndrome is SCN5A, but several other genes have also been implicated

Key genes associated with ARVC include:

SCN5A (Sodium Voltage-Gated Channel Alpha Subunit 5)

Mutations in the SCN5A gene are the most common cause of Brugada syndrome, accounting for approximately 20-30% of cases. SCN5A encodes the alpha subunit of the cardiac sodium channel Nav1.5, which plays a crucial role in the initiation and propagation of the cardiac action potential. Mutations in SCN5A can disrupt normal sodium channel function, leading to alterations in cardiac electrical activity and the characteristic ECG changes seen in Brugada syndrome.

CACNA1C (Calcium Voltage-Gated Channel Subunit Alpha1 C)

Mutations in the CACNA1C gene have been associated with a variant form of Brugada syndrome, known as Brugada syndrome 3. CACNA1C encodes the alpha subunit of the L-type calcium channel Cav1.2, which is involved in cardiac excitation-contraction coupling and the regulation of action potential duration. Mutations in CACNA1C can lead to abnormalities in calcium channel function and contribute to the development of Brugada syndrome.

SCN10A (Sodium Voltage-Gated Channel Alpha Subunit 10)

Mutations in the SCN10A gene have been linked to Brugada syndrome, particularly in cases where no mutations are found in SCN5A. SCN10A encodes the alpha subunit of the cardiac sodium channel Nav1.8, which is expressed in the heart and other tissues. Disruption of SCN10A function can affect cardiac conduction and increase the risk of arrhythmias characteristic of Brugada syndrome.

GPD1L (Glycerol-3-Phosphate Dehydrogenase 1-Like)

Mutations in the GPD1L gene have been associated with Brugada syndrome in some individuals. GPD1L encodes a protein involved in glycerol metabolism and may play a role in modulating cardiac sodium channel function. Mutations in GPD1L can lead to alterations in sodium channel activity and contribute to the development of Brugada syndrome.

HCN4 (Hyperpolarization-Activated Cyclic Nucleotide-Gated Potassium Channel 4)

Mutations in the HCN4 gene have been implicated in Brugada syndrome, particularly in cases with sinus node dysfunction and conduction abnormalities. HCN4 encodes the pacemaker channel responsible for the funny current (If) in the sinoatrial node. Disruption of HCN4 function can affect cardiac automaticity and contribute to arrhythmias observed in Brugada syndrome.

These genes play crucial roles in cardiac ion channel function and electrical conduction, and mutations in these genes can lead to the development of Brugada syndrome.

However, it's important to note that Brugada syndrome is a genetically heterogeneous disorder, and additional genes and genetic factors may also contribute to its pathogenesis. Genetic testing can help identify mutations associated with Brugada syndrome and guide clinical management and treatment decisions for affected individuals and their families.