| Title: | Copy number variants and their implications for developmental and behavioural problems in cleft lip and/or palate |
| Journal: | Human Molecular Genetics |
| Published: | 15 Jul 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40662303/ |
| DOI: | https://doi.org/10.1093/hmg/ddaf115 |
Publication 16994
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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.</p>
14 Keywords
- Behavior
- Child Behavior Disorders
- Child, Preschool
- Cleft Lip
- Cleft Palate
- DNA Copy Number Variations
- Developmental Disabilities
- Female
- Humans
- Infant
- Male
- Prevalence
- Risk
- United Kingdom
15 Authors
- Alexandros Rammos
- Rachel Blakey
- Charlotte A Dennison
- Sarah J Lewis
- Nabila Ali
- Amy Davies
- Yvonne Wren
- Kerry Humphries
- Jonathan Sandy
- Elliott Rees
- Kimberley Marie Kendall
- Gemma C Sharp
- Michael J Owen
- Marianne B M van den Bree
- Evie Stergiakouli
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