Martínez-Barrios Estefanía, Grassi Simone, Brión María, Toro Rocío, Cesar Sergi, Cruzalegui José, Coll Mònica, Alcalde Mireia, Brugada Ramon, Greco Andrea, Ortega-Sánchez María Luisa, Barberia Eneko, Oliva Antonio, Sarquella-Brugada Georgia, Campuzano Oscar
Pediatric Arrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Cardiology Department, Sant Joan de Déu Hospital de Barcelona, Barcelona, Spain.
European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart, Amsterdam, Netherlands.
Front Med (Lausanne). 2023 Feb 10;10:1118585. doi: 10.3389/fmed.2023.1118585. eCollection 2023.
In the forensic medicine field, molecular autopsy is the post-mortem genetic analysis performed to attempt to unravel the cause of decease in cases remaining unexplained after a comprehensive forensic autopsy. This negative autopsy, classified as negative or non-conclusive, usually occurs in young population. In these cases, in which the cause of death is unascertained after a thorough autopsy, an underlying inherited arrhythmogenic syndrome is the main suspected cause of death. Next-generation sequencing allows a rapid and cost-effectives genetic analysis, identifying a rare variant classified as potentially pathogenic in up to 25% of sudden death cases in young population. The first symptom of an inherited arrhythmogenic disease may be a malignant arrhythmia, and even sudden death. Early identification of a pathogenic genetic alteration associated with an inherited arrhythmogenic syndrome may help to adopt preventive personalized measures to reduce risk of malignant arrhythmias and sudden death in the victim's relatives, at risk despite being asymptomatic. The current main challenge is a proper genetic interpretation of variants identified and useful clinical translation. The implications of this personalized translational medicine are multifaceted, requiring the dedication of a specialized team, including forensic scientists, pathologists, cardiologists, pediatric cardiologists, and geneticists.
在法医学领域，分子尸检是指在全面的法医尸检后仍无法解释死因的情况下，为试图查明死因所进行的死后基因分析。这种被归类为阴性或非结论性的尸检结果通常出现在年轻人群体中。在这些经过彻底尸检仍无法确定死因的案例中，潜在的遗传性致心律失常综合征是主要的可疑死因。新一代测序技术能够实现快速且经济高效的基因分析，在年轻人群体高达25%的猝死病例中识别出被归类为潜在致病性的罕见变异。遗传性致心律失常疾病的首发症状可能是恶性心律失常，甚至是猝死。早期识别与遗传性致心律失常综合征相关的致病性基因改变，可能有助于采取预防性的个性化措施，降低受害者亲属发生恶性心律失常和猝死的风险，尽管他们没有症状但仍处于风险之中。当前的主要挑战是对所识别变异进行恰当的基因解读以及进行有效的临床转化。这种个性化转化医学的影响是多方面的，需要一个专业团队的投入，包括法医科学家、病理学家、心脏病专家、儿科心脏病专家和遗传学家。
