Differences between Multiplex and Simplex Autism: Does Parent Experience Contribute to Differences in Cognitive and Behavioural Development?

Background: It has been suggested that multiplex (MPX) and simplex (SPX) cases of Autism Spectrum Disorder (ASD) may originate from separate genetic aetiologies. Previous research examining differences between these groups has found that MPX children may possess and advantage in cognition and behaviour compared to SPX children suggesting that MPX and SPX groups represent different phenotypes. However, there are a number of limitations within the existing literature. In particular, samples have been biased by the inclusion of singleton children in the SPX group or the recruitment of MPX children from high-risk sibling cohorts, where only the second affected child is included. Further, research has also demonstrated that parental experience and knowledge contributes to improved outcomes for children with ASD. Existing studies examining MPX/SPX differences have not accounted for MPX parent’s previous experience with older diagnosed siblings, which may improve outcomes for these second affected MPX probands.

Objectives: The aim in this study was to expand on the literature regarding MPX/SPX differences by not only investigating the possible MPX advantage in a large database sample, but also evaluating if parent experience was a contributor. It was hypothesised that MPX children would demonstrate higher cognitive and adaptive behaviour scores and less ASD symptom severity than SPX counterparts. In addition, it was hypothesised that if parent experience was contributing to the apparent MPX advantage, MPX second affected children would demonstrate better cognitive and adaptive skills, and fewer ASD symptoms compared to their MPX first affected counterparts.

Methods: Four hundred and twenty-nine children from the Autism Genetic Resource Exchange (AGRE) were stratified into first- and second-affected MPX (MPX¹; n­=152, MPX²; n=143), SPX (n=111), and only-child SPX (SPX^OC; n=23) groups. Group differences were examined using scores from the Stanford-Binet 5^th edition, Mullen Scales of Early Learning, Vineland Adaptive Behaviour Scale, and the Autism Diagnostic Observation Schedule. Significant ANCOVA results were followed by post hoc comparisons between groups.

Results: No differences were found between MPX¹ and MPX² groups on any of the dependent variables. However, both MPX groups had significantly higher cognitive scores compared to the SPX group. Initially findings showed a significant difference between the MPX and SPX group for adaptive behaviour, such that the MPX group had higher scores compared to the SPX group. However, when cognition was included as a covariate in the analysis the difference was no longer significant. There were no significant differences between the groups on ASD symptom severity.

Conclusions: The current finding of a MPX advantage in cognitive functioning supports the view that MPX and SPX cases may represent different phenotypes of ASD. Further, the null findings between MPX¹ and MPX² infer parent experience is less likely to contribute substantially to differences between MPX and SPX groups. Overall, these results suggest that research regarding cognitive functioning in ASD should take into account MPX and SPX status as these groups appear to differ in their cognitive abilities and thus represent separate phenotypes of ASD.