Quantitative trait variation in ASD probands and toddler sibling outcomes at 24 months
Quantitative trait variation in ASD probands and toddler sibling outcomes at 24 months
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DOI：
10.1186/s11689-020-9308-7
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发表时间：
2020-02-05
影响因子：
4.9
通讯作者：
Shen, M.
中科院分区：
文献类型：
--
作者：
Girault, Jessica B.;Swanson, Meghan R.;Shen, M.
自闭症谱系障碍（ASD）儿童的弟弟妹妹接受ASD诊断并表现出其他发育问题的可能性增加。目前尚不清楚ASD性状的数量变化和ASD（先证者）年长兄弟姐妹更广泛的发展领域如何影响其年幼兄弟姐妹的结果。方法参与者包括385对幼儿兄弟姐妹和婴儿脑成像研究的先证者。ASD先证者（平均年龄5.5岁，范围1.7至15.5岁）使用自闭症诊断访谈修订版（ADI-R），社会沟通问卷（SCQ）和葡萄园适应行为量表，第二版（VABS-II）进行表型分析。使用ADI-R、VABS-II、马伦早期学习量表（MSEL）和自闭症诊断观察表（ADOS）对自闭症进行评估，并在24个月时使用DSM-IV-TR标准进行临床最佳估计诊断（ASD一致n = 89;不一致n = 296）。我们致力于两个目标：（1）确定先证者特征是否可预测同胞复发;（2）评估先证者特征与24个月时同胞维度结局之间的关联。结果关于复发风险，发现先证者SCQ评分显著预测兄弟姐妹24个月的诊断结果（SCQ增加1分的OR = 1.06; 95%CI = 1.01，1.12）。关于数量性状的关联，我们发现先证者-同胞对之间的ASD性状没有显着相关性。然而，先证者适应性行为、交流、表达和接受性语言的数量变化与相同领域的兄弟姐妹结果显著相关;先证者评分解释了ASD兄弟姐妹认知和行为变化的9-18%。接受性语言在一致性配对中的相关性特别强（ICC = 0.50，p < 0.001）。结论先证者的ASD家族史，以SCQ为指标，是家族性ASD复发风险的预测因子。虽然社会沟通和限制和重复行为的数量变化在兄弟姐妹之间没有相关性，但先证者语言和沟通的标准化评级解释了24个月时兄弟姐妹中相同领域的显着变化，特别是在ASD诊断的幼儿中。这些数据表明，先证者的特征可以提醒临床医生对有ASD家族风险的幼儿的发育问题。
Background Younger siblings of children with autism spectrum disorder (ASD) are at increased likelihood of receiving an ASD diagnosis and exhibiting other developmental concerns. It is unknown how quantitative variation in ASD traits and broader developmental domains in older siblings with ASD (probands) may inform outcomes in their younger siblings. Methods Participants included 385 pairs of toddler siblings and probands from the Infant Brain Imaging Study. ASD probands (mean age 5.5 years, range 1.7 to 15.5 years) were phenotyped using the Autism Diagnostic Interview-Revised (ADI-R), the Social Communication Questionnaire (SCQ), and the Vineland Adaptive Behavior Scales, Second Edition (VABS-II). Siblings were assessed using the ADI-R, VABS-II, Mullen Scales of Early Learning (MSEL), and Autism Diagnostic Observation Schedule (ADOS) and received a clinical best estimate diagnosis at 24 months using DSM-IV-TR criteria (n = 89 concordant for ASD; n = 296 discordant). We addressed two aims: (1) to determine whether proband characteristics are predictive of recurrence in siblings and (2) to assess associations between proband traits and sibling dimensional outcomes at 24 months. Results Regarding recurrence risk, proband SCQ scores were found to significantly predict sibling 24-month diagnostic outcome (OR for a 1-point increase in SCQ = 1.06; 95% CI = 1.01, 1.12). Regarding quantitative trait associations, we found no significant correlations in ASD traits among proband-sibling pairs. However, quantitative variation in proband adaptive behavior, communication, and expressive and receptive language was significantly associated with sibling outcomes in the same domains; proband scores explained 9-18% of the variation in cognition and behavior in siblings with ASD. Receptive language was particularly strongly associated in concordant pairs (ICC = 0.50, p < 0.001). Conclusions Proband ASD symptomology, indexed by the SCQ, is a predictor of familial ASD recurrence risk. While quantitative variation in social communication and restricted and repetitive behavior were not associated among sibling pairs, standardized ratings of proband language and communication explained significant variation in the same domains in the sibling at 24 months, especially among toddlers with an ASD diagnosis. These data suggest that proband characteristics can alert clinicians to areas of developmental concern for young children with familial risk for ASD.