Abstract
BackgroundYounger 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.MethodsParticipants 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.ResultsRegarding 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).ConclusionsProband 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.
Highlights
Autism spectrum disorder (ASD) is a highly heritable [1] neurodevelopmental disorder diagnosed in 1–2% of children [2]
For each additional point a proband scored on the Proband-sibling associations: cognition and behavior Distributions of the VABS-II scores for probands and toddler siblings are depicted in Fig. 1, and a comparison of proband and sibling measures is presented in Additional file 1: Table S3
For scores on the VABS-II, significant Intraclass correlation (ICC) for concordant pairs were found for Adaptive Behavior Composite (ABC), SOC, and COM composite scores and the Expressive language (EL) and Receptive language (RL) scale scores (Table 3)
Summary
Autism spectrum disorder (ASD) is a highly heritable [1] neurodevelopmental disorder diagnosed in 1–2% of children [2]. While fewer large-scale studies have investigated the familial aggregation of ASD symptom domains, there is evidence that nonverbal communication and social impairments are correlated among affected sibling pairs [8, 14], with nonverbal communication being most heritable [15]. 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
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