Early Manifestations of Neurodevelopmental Copy Number Variants in Children: A Population-Based Investigation

There is clinical interest in recognizing copy number variants (CNVs) in children because many have immediate and long-term health implications. Neurodevelopmental (ND) CNVs are associated with intellectual disability, autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD), conditions typically diagnosed by medical practitioners. However, ND CNVs may have additional, early developmental impacts that have yet to be examined in unselected populations.

Carriers of known ND CNVs were identified in 2 UK birth cohorts: ALSPAC (Avon Longitudinal Study of Parents and Children) (carriers = 144, controls = 6217) and MCS (Millennium Cohort Study) (carriers = 151, controls = 6559). In ALSPAC, we assessed associations between CNV carrier status and birth complications; preschool development; cognitive ability; ND conditions (ASD, ADHD, reading, language, and motor difficulties); and psychiatric, social, and educational outcomes. Corresponding phenotypes were identified in MCS and meta-analyzed, where available.

In ALSPAC, ND CNVs were associated with low cognitive ability, ADHD, and ASD. ND CNV carriers showed a greater likelihood of preterm birth, fine and gross motor delay, difficulties in motor coordination, language, and reading, and special educational needs (SEND). Meta-analysis with available measures in MCS identified elevated likelihood of ASD, ADHD, low birth weight, reading difficulties, SEND, and peer problems.

ND CNVs are associated with a broad range of developmental impacts. While clinicians who see children with intellectual disability, ASD, or ADHD may be aware of the impacts of CNVs and consider genetic testing, our investigation suggests that this training and awareness may need to extend to other professional groups (e.g., speech and language therapists).