Clinical correlates in children with autism spectrum disorder and CNVs: Systematic investigation in a clinical setting

Autism spectrum disorder (ASD) is associated with various molecular mechanisms including copy number variants (CNVs). We investigated possible associations between CNVs and ASD clinical correlates. We evaluated pertinent physical characteristics and phenotypic measures such as cognitive level, severity of ASD symptoms and comorbid conditions in ASD patients consecutively recruited over the study period. Children with causative (C-CNVs), non-causative (NC-CNVs) and without CNVs (W-CNVs) were compared. Out of 109 patients, 31 imbalances (16 duplications and 15 deletions) were detected in 25 subjects. Seven (6.4%) had C-CNVs and 18 (16.5%) had NC-CNVs. Paired post hoc comparisons with Bonferroni adjustment showed that dysmorphisms and microcephaly were significantly more frequent in the C-CNVs group. Patients with C-CNVs had more severe autistic core symptoms, while comorbid internalizing behavioral symptoms were more represented among participants with NC-CNVs. No significant differences were observed for distribution of macrocephaly, intellectual disability, epilepsy, isolated electroencephalogram abnormalities and studied neuroimaging characteristics among groups. Recurrent and rare C-CNVs highlighting genes relevant to neurodevelopment had a statistically higher occurrence in children with more severe ASD symptoms and further developmental abnormalities. This study documents the importance of measuring the physical and neurobehavioural correlates of ASD phenotypes to unravel the underlying molecular mechanisms in patient subgroups.