Brugada syndrome is a heritable channelopathy characterized by a peculiar electrocardiogram (ECG) pattern and increased risk of cardiac arrhythmias and sudden death. The arrhythmias originate because of an imbalance between the repolarizing and depolarizing currents that modulate the cardiac action potential. Even if an overt structural cardiomyopathy is not typical of Brugada syndrome, fibrosis and structural changes in the right ventricle contribute to a conduction slowing, which ultimately facilitates ventricular arrhythmias. Currently, Mendelian autosomal dominant transmission is detected in less than 25% of all clinical confirmed cases. Although 23 genes have been associated with the condition, only SCN5A, encoding the cardiac sodium channel, is considered clinically actionable and disease causing. The limited monogenic inheritance has pointed toward new perspectives on the possible complex genetic architecture of the disease, involving polygenic inheritance and a polygenic risk score that can influence penetrance and risk stratification.

中文翻译：

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布鲁格达综合征的遗传学

Brugada 综合征是一种遗传性通道病，其特征是特殊的心电图 (ECG) 模式以及心律失常和猝死的风险增加。心律失常是由于调节心脏动作电位的复极电流和去极化电流之间的不平衡而引起的。即使明显的结构性心肌病不是布鲁格达综合征的典型特征，右心室的纤维化和结构变化也会导致传导减慢，最终导致室性心律失常。目前，在所有临床确诊病例中，不到 25% 检测到孟德尔常染色体显性遗传。尽管有 23 个基因与该病症相关，但只有编码心脏钠通道的 SCN5A 被认为具有临床作用并导致疾病。有限的单基因遗传为该疾病可能的复杂遗传结构提供了新的视角，包括多基因遗传和可以影响外显率和风险分层的多基因风险评分。