Abstract

Sleep difficulties are pervasive in autism spectrum disorder (ASD), yet how sleep problems relate to underlying biological mechanisms such as genetic etiology is unclear, despite recent reports of profound sleep problems in children with ASD-associated de novo likely gene disrupting (dnLGD) mutations, CHD8, DYRK1A, and ADNP. We aimed to inform etiological contributions to ASD and sleep by characterizing sleep problems in individuals with dnLGD mutations. Participants (N = 2886) were families who completed dichotomous questions about sleep problems within a medical history interview for their child with ASD (age 3-28 years). Confirmatory factor analyses compared between those with ASD and a dnLGD mutation and those with idiopathic ASD (i.e., no known genetic event, NON) highlighted four domains (sleep onset, breathing issues, nighttime awakenings, and daytime tiredness) with sleep onset as a strong factor for both groups. Overall, participant predictors indicated that internalizing behavioral problems and lower cognitive scores were related to increased sleep problems. Internalizing problems were also related to increase nighttime awakenings in the dnLGD group. As an exploratory aim, patterns of sleep issues are described for genetic subgroups with unique patterns including more overall sleep issues in ADNP (n = 19), problems falling asleep in CHD8 (n = 22), and increased daytime naps in DYRK1A (n = 23). Implications for considering genetically defined subgroups when approaching sleep problems in children with ASD are discussed.

摘要

睡眠困难在自闭症谱系障碍 (ASD) 中普遍存在，但睡眠问题与遗传病因等潜在生物学机制的关系尚不清楚，尽管最近有报道称患有 ASD 相关的从头可能基因破坏 (dnLGD) 突变的儿童存在严重的睡眠问题、CHD8、DYRK1A和ADNP. 我们旨在通过描述具有 dnLGD 突变的个体的睡眠问题来告知 ASD 和睡眠的病因学贡献。参与者 (N = 2886) 是在为患有 ASD 的孩子（3-28 岁）的病史访谈中完成关于睡眠问题的二分法问题的家庭。对患有 ASD 和 dnLGD 突变的患者与患有特发性 ASD（即无已知遗传事件，NON）的患者进行比较的验证性因素分析强调了四个领域（入睡、呼吸问题、夜间觉醒和白天疲倦），其中入睡是强两组因素。总体而言，参与者预测指标表明，内化行为问题和较低的认知评分与睡眠问题增加有关。内化问题也与 dnLGD 组夜间觉醒的增加有关。ADNP ( n = 19)， CHD8 入睡问题( n  = 22)，DYRK1A白天小睡增加( n  = 23)。讨论了在处理 ASD 儿童睡眠问题时考虑遗传定义的亚组的意义。