Motor- and Sex-Related Autism Phenotypes Within 16p11.2 Copy Number Variants

Abstract

Autism spectrum disorder (ASD) is a behaviorally defined condition, largely characterized by social deficits and both restricted and repetitive behaviors and interests. Despite its absence from diagnostic criteria, motor impairment (e.g., developmental coordination disorder) is also present in the majority of individuals with ASD. Genetics-first studies have demonstrated that certain copy number variants (CNV) within the 16p11.2 chromosomal region pose risk for both motor impairment and ASD. Given evidence that 16p11.2 CNVs show considerable heterogeneity in phenotypic features, the present study aimed to further explore the relationship between genetic risk, motor impairment, and ASD. By exploring phenotypic features of 16p-deletion and 16p-duplication carriers, the study also sought to determine if motor development varied as a function of sex. Participants included 689 individuals with and without 16p11.2 CNVs from the Simons Searchlight project. Analyses revealed that deletion and duplications carriers of 16p11.2 showed significantly more motor impairment than non-carrier siblings. Further, 16p-deletion posed significantly higher risk for motor impairment than 16p-duplication in young carriers. In children under 6-years, males and females with a 16p11.2 CNV were also at equally high risk for motor impairment. In adults, 16p11.2 was still associated with significantly more motor impairment compared to neurotypical counterparts. Finally, regression analyses revealed genetic risk to be a strong predictor of motor impairment after controlling for sex, age, IQ, and ASD diagnosis. The results of the present study have implications for the diagnostic utility of motor functioning. Early screening and referral practices for ASD would benefit from routine consideration of motor development in order to trigger a referral for genetic testing as well as appropriate interventions and evaluations. A consideration of motor functioning also has opportunities to improve the age of diagnosis for females, a group that is relatively under-identified. Taken together, these findings support a consideration of both genetic risk and motor impairment in early screening and diagnostic practices of ASD.