Division of Genetics, Program in Genomics, and Manton Center for Orphan Disease Research, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts 02115, USA.
Pediatr Neurol. 2012 Apr;46(4):235-9. doi: 10.1016/j.pediatrneurol.2012.02.007.
Sudden unexplained death in toddlers has been associated with febrile seizures, family history of febrile seizures, and hippocampal anomalies. We investigated the mode of inheritance for febrile seizures in these families. A three-generation pedigree was obtained from families enrolled in the San Diego Sudden Unexplained Death in Childhood Research Project, involving toddlers with sudden unexplained death, febrile seizures, and family history of febrile seizures. In our six cases, death was unwitnessed and related to sleep. The interval from last witnessed febrile seizure to death ranged from 3 weeks to 6 months. Hippocampal abnormalities were identified in one of three cases with available autopsy sections. Autosomal dominant inheritance of febrile seizures was observed in three families. A fourth demonstrated autosomal dominant inheritance with incomplete penetrance or variable expressivity. In two families, the maternal and paternal sides manifested febrile seizures. In this series, the major pattern of inheritance in toddlers with sudden unexplained death and febrile seizures was autosomal dominant. Future studies should develop markers (including genetic) to identify which patients with febrile seizures are at risk for sudden unexplained death in childhood, and to provide guidance for families and physicians.
婴幼儿突发性不明原因死亡与热性惊厥、热性惊厥家族史和海马异常有关。我们研究了这些家族热性惊厥的遗传方式。从参与圣地亚哥婴幼儿突发性不明原因死亡研究项目的家庭中获得了一个三代系谱，涉及突发性不明原因死亡、热性惊厥和热性惊厥家族史的婴幼儿。在我们的 6 个病例中，死亡发生在睡眠中且无人见证。从最后一次有目击者的热性惊厥到死亡的间隔时间从 3 周到 6 个月不等。在有可用尸检切片的 3 例中，有 1 例发现了海马异常。在 3 个家族中观察到热性惊厥呈常染色体显性遗传。第四个表现为不完全外显或表现度可变的常染色体显性遗传。在 2 个家族中，母亲和父亲双方均表现出热性惊厥。在本系列中，突发性不明原因死亡和热性惊厥婴幼儿的主要遗传方式为常染色体显性遗传。未来的研究应该开发标志物（包括遗传标志物），以识别哪些热性惊厥患者有发生儿童突发性不明原因死亡的风险，并为患者及其家属和医生提供指导。
