Copy number variants and their implications for developmental and behavioural problems in cleft lip and/or palate

Rammos, Alexandros, Blakey, Rachel, Dennison, Charlotte A. ORCID: https://orcid.org/0000-0002-7493-2041, Lewis, Sarah J., Ali, Nabila, Davies, Amy, Wren, Yvonne, Humphries, Kerry, Sandy, Jonathan, Rees, Elliott ORCID: https://orcid.org/0000-0002-6168-9222, Kendall, Kimberley Marie ORCID: https://orcid.org/0000-0002-6755-6121, Sharp, Gemma C., Owen, Michael J. ORCID: https://orcid.org/0000-0003-4798-0862, van den Bree, Marianne B. M. ORCID: https://orcid.org/0000-0002-4426-3254 and Stergiakouli, Evie 2025. Copy number variants and their implications for developmental and behavioural problems in cleft lip and/or palate. Human Molecular Genetics 34 (18) , pp. 1563-1574. 10.1093/hmg/ddaf115

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Abstract

Cleft lip and/or palate (CL/P) is the most common craniofacial congenital anomaly and has been associated with higher risk of neurodevelopmental and behavioural problems indicating potential shared genetic factors between CL/P and neurodevelopmental disorders. In this study, we aimed to determine the prevalence of neurodevelopmental copy number variants (CNV) in children with CL/P and their link to early developmental and behavioural problems. Using data from the Cleft Collective, the largest UK-based national cohort study of children with CL/P, we determined the rates of neurodevelopmental CNVs in children with CL/P comparing them to the general population, explored differences by cleft type and investigated risk of developmental delays and behavioural problems among those with CL/P and neurodevelopmental CNVs. Children with CL/P had a higher prevalence of neurodevelopmental CNVs than participants in four population-based samples (3.7% vs 2.3% in the Avon Longitudinal Study of Parents and Children (ALSPAC), 2.0% in Born in Bradford (BiB), 2.3% in Millenium Cohort Study (MCS), 1.7% in UK Biobank, ORs(95%CIs): ALSPAC = 1.56(1.18–2.06), BiB = 1.84(1.37–2.45), MCS = 1.59(1.19–2.11), UK Biobank = 2.15(1.68–2.71). Children with cleft palate only were 3 times more likely to have a neurodevelopmental CNV (95%CIs1.50–6.59, p = 0.03) than children with cleft lip only. Furthermore, children with CL/P and neurodevelopmental CNVs were more likely to experience early developmental delays and behavioural problems by age 5 compared to children with CL/P and without neurodevelopmental CNVs. These findings highlight that genetic testing ascertaining the presence of neurodevelopmental CNVs might be helpful in early identification of developmental needs in children with CL/P.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Additional Information:	License information from Publisher: LICENSE 1: URL: https://creativecommons.org/licenses/by/4.0/, Type: cc-by
Publisher:	Oxford University Press
ISSN:	0964-6906
Date of First Compliant Deposit:	23 July 2025
Date of Acceptance:	20 June 2025
Last Modified:	09 Sep 2025 12:18
URI:	https://orca.cardiff.ac.uk/id/eprint/179992

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