Sudden Unexplained Death in Childhood (SUDC) needs to be fully assessed considering its impact on the family, parents and siblings. Inborn Errors of Metabolism (IEM) such as Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCADD) should be taken into consideration when SUDC occurres. Our aim is to present a family with two successive SUDC and to discuss the post-mortem genetics investigations revealing an IEM implication. A complete autopsy with genetic testing was performed when the proband, a 4-year-old girl, died. A few years previously, her older brother had died at the same age and off the same condition. Years later, his exhumation was necessary in order to perform a post-mortem diagnosis.The two siblings were revealed to have had the same pathogenic genotype of the gene, heterozygous substitutions in (NM_000016.5): c.985A>G p.(Lys329Glu) and c.347G>A p.(Cys116Tyr). In addition, they also both carried a VUS in , a gene implicated in Catecholaminergic Polymorphic Tachycardia Ventricular (CPVT) and SUDC. We illustrate the importance of exome analyses for investigating unexplained sudden death, especially in children, with the possible impact for genetic counselling in the family. The finding of the implication of gene in this case, raises likely responsibility of the public health system in countries such as France, who delayed implementation of new born screening for these conditions. Exome analyses in this case detected unexpected complexity in interpretation linked to the identification of a second candidate gene for SUDC.

中文翻译：

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反复发生的儿童早期猝死家族病例：复杂的尸检遗传学研究

考虑到儿童期不明原因猝死 (SUDC) 对家庭、父母和兄弟姐妹的影响，需要对其进行全面评估。发生 SUDC 时，应考虑先天性代谢缺陷 (IEM)，例如中链酰基辅酶 A 脱氢酶缺乏症 (MCADD)。我们的目的是展示一个连续两次发生 SUDC 的家庭，并讨论揭示 IEM 影响的死后遗传学研究。先证者（一名 4 岁女孩）死亡时，进行了完整的尸检和基因检测。几年前，她的哥哥在同样的年纪、同样的情况下去世了。多年后，为了进行尸检诊断，需要对他进行尸检。两个兄弟姐妹被发现具有相同的致病基因型，即(NM_000016.5)中的杂合取代：c.985A>G p。( Lys329Glu) 和 c.347G>A p.(Cys116Tyr)。此外，它们还都携带 VUS，该基因与儿茶酚胺能多形性室性心动过速 (CPVT) 和 SUDC 有关。我们阐述了外显子组分析对于调查不明原因猝死的重要性，尤其是儿童猝死，以及对家庭遗传咨询的可能影响。在该病例中发现基因的影响，可能需要法国等国家的公共卫生系统承担责任，这些国家推迟了针对这些疾病的新生儿筛查的实施。在这种情况下，外显子组分析发现了与 SUDC 的第二个候选基因的鉴定相关的解释中意想不到的复杂性。