Abstract Background: Several recent initiatives have sought to better understand characteristic behaviors of rare genetic conditions associated with autism spectrum disorder (ASD). The onset of developmentally expected skills, such as walking and talking, serve as readily quantifiable aspects of the behavioral phenotype. The goals of this study were to describe attainment of major motor and language milestones in genetic conditions implicated in the etiology of ASD and other neurodevelopmental disorders and to compare those phenotypes to idiopathic ASD. Methods: Participants ages 3 years and older were drawn from two Simons Foundation Autism Research Initiative-funded registries with consistent phenotyping protocols. Inclusion criteria consisted of a confirmed genetic diagnosis for one of 16 specific genetic conditions (Simons Searchlight), and absence of pathogenic genetic findings in idiopathic ASD controls (SPARK). Parent-reported age of acquisition of three motor and two language milestones was described and quantified as on-time or delayed relative to normative expectations. Results: Delay was more common among participants with rare genetic conditions than idiopathic ASD for all milestones. Compared to the idiopathic ASD group, the median odds of delay among the genetic groups were 8.3 times (IQR 5.8-16.3) higher for sitting, 12.4 times (IQR 5.3-19.5) higher for crawling, 26.8 times (IQR 7.7-41.1) higher for walking, 2.7 times (IQR 1.7-5.5) higher for single words, and 5.7 times (IQR 2.8-18.3) higher for combined words. Conclusion: Delays in major developmental milestones, particularly in motor skills, may be among the earliest clues that developmental processes may be differentially affected in specific genetically defined conditions versus a behaviorally defined disorder such as idiopathic ASD.

中文翻译：

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SFARI注册管理机构在遗传条件方面的里程碑式发展

摘要背景：最近的一些举措试图更好地了解与自闭症谱系障碍（ASD）相关的罕见遗传病的特征行为。诸如步行和交谈之类的发展预期技能的发作是行为表型的易于量化的方面。这项研究的目的是描述与ASD和其他神经发育障碍的病因有关的遗传条件下主要运动和语言里程碑的实现，并将这些表型与特发性ASD进行比较。方法：年龄3岁及以上的参与者来自两个西蒙斯基金会自闭症研究计划资助的，具有一致表型研究方案的注册管理机构。纳入标准包括对16种特定遗传疾病之一的确诊遗传诊断（Simons Searchlight），特发性ASD对照（SPARK）中没有致病的遗传学发现。父母报告的获得三个运动和两个语言里程碑的年龄被描述并量化为准时或相对于规范性期望的延迟。结果：就所有里程碑而言，在遗传条件罕见的参与者中，延误比特发性ASD更为普遍。与特发性ASD组相比，基因组中位延迟的中位几率是坐着时高8.3倍（IQR 5.8-16.3），爬行时高12.4倍（IQR 5.3-19.5），高26.8倍（IQR 7.7-41.1）步行时，单个单词的搜索量高2.7倍（IQR 1.7-5.5），而组合单词的搜索量高5.7倍（IQR 2.8-18.3）。结论：主要发展里程碑的延迟，特别是运动技能的延迟，