Utilizing the SRS-P to Examine ASD Symptoms in a Sample of High-Risk Toddlers with Neurogenetic Syndromes

Background: Elevated rates of psychopathology such as autism spectrum disorders (ASD) are common in individuals with neurogenetic syndromes (NGS), including Angelman (AS; 63%), Prader-Willi (PWS; 23%), and Williams (WS; 50%) syndromes. ASD prevalence in these populations is highly elevated compared to 2% in the general population and 20% in siblings of a child with ASD (Baio et al., 2018; Betancur & Coleman, 2013; Ozonoff et al., 2011). Comparing early social responsivity across multiple NGS at increased risk for ASD may elucidate potential pathways of ASD by informing which phenotypic features differentially map on to each NGS, as the genetic mechanisms underlying each NGS are relatively well understood. Some reports suggest differences in social cognition and the underlying processes within NGS (Morel & Demily, 2017), however, very little is known about the early phenotypic profiles of ASD symptomatology in toddlers who are likely most naïve to interventions.

Objectives: To examine differences in early ASD symptomology in toddlers at increased genetic risk for ASD.

Methods: 98 caregivers of toddlers with AS (n=23), PWS (n=18), WS (n=31), and low-risk controls (LRC; n=26) completed the Social Responsiveness Scale Preschool Age, 2^nd Edition (SRS-P) as part of an online, longitudinal study of early development. The 65-item SRS-P is rated from 1 (not true) to 4 (almost always) and identifies social impairment associated with ASD. T-scores are generated for Overall Social Deficits and five subscales: social awareness (SA), social cognition (COG), social communication (COM), social motivation (MOT), and restricted interests and repetitive behavior (RRB). We used Kruskal-Wallis tests to test omnibus group differences for SRS scores and Dunn’s post-hoc procedure with Bonferroni correction to probe pairwise comparisons.

Results: Age (M=36.33 months, SD=5.11, Kruskal-Wallis Χ²(3)=1.12, p=.773) and sex (47% female, Χ²(3)=4.50, p=.212) did not differ across groups. The distributions of each SRS score significantly differed across groups (ps<.01). Post-hoc analyses revealed that relative to LRC, NGS groups demonstrated significantly higher t-scores on Overall Social Deficits and SA, COM, and RRB subscales (ps<.01), but NGS groups did not differ from one another. However, this pattern differed for COG and MOT subscales. On the COG subscale, AS and WS (medians [Mdns]=64, ps<.001) were significantly higher than LRC (Mdn=42), but PWS (Mdn=51) did not differ from LRC (p=.057). Additionally, on the COG subscale, PWS was significantly lower than both AS and WS (ps=.007). On the MOT subscale, AS (Mdn=51) was significantly higher than LRC (Mdn=45, p=.023), with no other differences between groups (ps>.05).

Conclusions: Results suggest that although toddlers with NGS consistently exhibit atypical social responsiveness symptoms compared to LRC, more nuanced patterns present across NGS groups, particularly in relation to social cognition and social motivation. These findings provide preliminary evidence that although multiple NGS exhibit heightened risk for ASD, the genetic mechanisms and associated profiles related to these risks may vary. Continuing to probe these differences in an expanded longitudinal cohort may further inform how and why different NGS are more highly impacted by ASD, as well as potential models of differential detection and intervention.