Brlek Petar, Pavelić Eduard Stjepan, Mešić Jana, Vrdoljak Kristijan, Skelin Andrea, Manola Šime, Pavlović Nikola, Ćatić Jasmina, Matijević Gordana, Brugada Josep, Primorac Dragan
St. Catherine Specialty Hospital, Zagreb, Croatia.
School of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia.
Front Cardiovasc Med. 2023 Sep 6;10:1193878. doi: 10.3389/fcvm.2023.1193878. eCollection 2023.
Brugada syndrome is a rare hereditary disorder characterized by distinct ECG findings, complex genetics, and a high risk of sudden cardiac death. Recognition of the syndrome is crucial as it represents a paradigm of sudden death tragedy in individuals at the peak of their lives. Notably, Brugada syndrome accounts for more than 20% of sudden cardiac deaths in individuals with structurally normal hearts. Although this syndrome follows an autosomal dominant inheritance pattern, it is more prevalent and severe in males. Diagnosis is primarily based on the characteristic ECG pattern observed in the right precordial leads. Mutations in the SCN5A gene, resulting in loss of function, are the most common genetic cause. We presented a 36-year-old proband with a family history of sudden cardiac death. Although the patient was asymptomatic for Brugada syndrome, his father had experienced sudden death at the age of 36. The proband was admitted to St. Catherine's Specialty Hospital where blood was taken and subjected to next-generation sequencing (NGS) using a "Sudden cardiac death" panel. The analysis identified a pathogenic variant in the SCN5A gene [c.4222G > A(p.Gly1408Arg)], which is associated with autosomal dominant Brugada syndrome. Based on the positive genetic test result, the patient was referred for further examination. ECG with modified precordial lead positioning confirmed the presence of the Brugada phenotype, displaying the type-2 and type-1 ECG patterns. Therefore, we made the diagnosis and decided to implant an implantable cardioverter-defibrillator (ICD) based on the results of broad genetic NGS testing, diagnostic criteria (ECG), and considering the high burden of sudden cardiac death in the patient's family, as well as his concerns that limited his everyday activities. This case shows that genetics and personalized medicine hold immense potential in the primary prevention, diagnosis, and treatment of Brugada syndrome and sudden cardiac death.
Brugada综合征是一种罕见的遗传性疾病,其特征为独特的心电图表现、复杂的遗传学机制以及心脏性猝死的高风险。认识该综合征至关重要,因为它代表了处于生命巅峰期的个体猝死悲剧的一种范例。值得注意的是,Brugada综合征在心脏结构正常的个体中占心脏性猝死的20%以上。尽管该综合征遵循常染色体显性遗传模式,但在男性中更为普遍且严重。诊断主要基于右胸前导联观察到的特征性心电图模式。SCN5A基因突变导致功能丧失是最常见的遗传原因。我们报告了一名36岁的先证者,其有心脏性猝死家族史。尽管该患者无Brugada综合征症状,但他的父亲在36岁时经历了猝死。该先证者入住圣凯瑟琳专科医院,采集血液并使用“心脏性猝死”检测板进行下一代测序(NGS)。分析确定SCN5A基因存在一个致病变异[c.4222G>A(p.Gly1408Arg)],这与常染色体显性Brugada综合征相关。基于阳性基因检测结果,该患者被转诊进行进一步检查。采用改良胸前导联定位的心电图证实了Brugada表型的存在,显示2型和1型心电图模式。因此,我们根据广泛的基因NGS检测结果、诊断标准(心电图),并考虑到患者家族中心脏性猝死的高负担以及他因担心而限制日常活动,做出诊断并决定植入植入式心律转复除颤器(ICD)。该病例表明,遗传学和个性化医疗在Brugada综合征和心脏性猝死的一级预防、诊断和治疗中具有巨大潜力。