Early manifestations of neurodevelopmental copy number variants in children: A population-based investigation.

Abstract

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

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

Results: In ALSPAC, neurodevelopmental CNVs were associated with low cognitive ability, ADHD and ASD. Neurodevelopmental CNV carriers showed 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 birthweight, reading difficulties, SEND, and peer problems.

Discussion: Neurodevelopmental 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).