Infantile spasms of unknown cause: predictors of outcome and genotype-phenotype correlation Yuskaitis CJ, Ruzhnikov MRZ, Howell KB, et al. Pediatr Neurol. 2018;87:48-56. doi:10.1016/j.pediatrneurol.2018.04.012. Epub 2018 May 7. BACKGROUND No large-scale studies have specifically evaluated the outcomes of infantile spasms (IS) of unknown cause, previously known as cryptogenic or idiopathic. The Epilepsy Phenome/Genome Project (EPGP) aimed to characterize IS of unknown cause by phenotype and genotype analysis. METHODS We undertook a retrospective multicenter observational cohort of 133 individuals within the EPGP database met criteria for IS of unknown cause with at least 6 months of follow-up data. Clinical medical records, imaging, and electroencephalography were examined. RESULTS Normal development occurred in only 15% of IS of unknown cause. The majority (85%) had clinically documented developmental delay (15% mild, 20% moderate, and 50% severe) at last assessment (median 2.7 years; interquartile interval 1.71-6.25 years). Predictors of positive developmental outcomes included no delay prior to IS ( P < .001), older age of IS onset (median 6 months old), and resolution of IS after initial treatment ( P < .001). Additional seizures after IS occurred in 67%, with predictors being seizures prior to IS ( P = .018), earlier age of IS onset (median 5 months old), and refractory IS ( P = .008). On a research basis, whole exome sequencing identified 15% with de novo variants in known epilepsy genes. Individuals with a genetic finding were more likely to have poor developmental outcomes ( P = .035). CONCLUSIONS The current study highlights the predominately unfavorable developmental outcomes and that subsequent seizures are common in children with IS of unknown cause. Ongoing genetic evaluation of IS of seemingly unknown cause is likely to yield a diagnosis and provide valuable prognostic information.

中文翻译：

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原因不明的小儿痉挛：谁能有好的结果？

病因不明的小儿痉挛：预后和基因型-表型相关性的预测因子Yuskaitis CJ，Ruzhnikov MRZ，Howell KB等。小儿神经。2018; 87：48-56。doi：10.1016 / j.pediatrneurol.2018.04.012。Epub 2018年5月7日。背景尚无大规模研究专门评估未知原因（先前称为隐源性或特发性）的婴儿痉挛症（IS）的结果。癫痫现象/基因组计划（EPGP）旨在通过表型和基因型分析来表征原因不明的IS。方法我们对EPGP数据库中的133名个体进行了回顾性多中心观察性队列研究，这些个体符合至少6个月的随访资料的不明原因IS的标准。检查了临床病历，影像学和脑电图。结果只有未知原因的IS中有15％发生了正常发育。在上次评估时（中位2.7年；四分位间隔为1.71-6.25年），大多数（85％）有临床记录的发育延迟（轻度15％，中度20％和重度50％）。积极的发展结果的预测因素包括：IS发生之前没有延迟（P <.001），IS发作的年龄较大（中位数为6个月）以及初始治疗后IS的消退（P <.001）。IS后发生癫痫发作的比例为67％，预测因素为IS发作前的癫痫发作（P = .018），IS发作的年龄较早（中位数5个月）和难治性IS（P = .008）。在研究的基础上，整个外显子组测序确定了已知癫痫基因中从头变异的15％。有遗传发现的个体更可能具有较差的发育结果（P = .035）。结论当前的研究强调了主要不利的发育结果，并且随后的癫痫发作在原因不明的IS儿童中很常见。对似乎原因未知的IS进行持续的遗传评估可能会产生诊断并提供有价值的预后信息。