An Original Investigation into the Genetic Epidemiology of Cleft Lip and Palate in Nigerian Families

Cleft lip and palate has both environmental and genetic determinants, and characterising the specific genetic variants contributing to CLP risk in Nigerian families provides original contributions to craniofacial genetics with direct implications for genetic counselling and preventive interventions. This study conducted an original genetic epidemiological investigation of cleft lip and palate in Nigerian families attending cleft treatment centres at University of Nigeria Teaching Hospital Enugu and Lagos University Teaching Hospital. A case-family study enrolled 148 unrelated CLP cases, 148 unaffected parents, and 148 unaffected matched controls. Candidate gene polymorphisms in IRF6, MTHFR, TGF-alpha, and FOXE1 were genotyped by PCR-RFLP and Sanger sequencing. Family history of CLP, periconceptional folate supplementation, maternal smoking and alcohol, and birth order data were collected. IRF6 V274I polymorphism showed a significantly increased CLP risk (OR = 2.41, 95% CI: 1.46 to 3.98, p < 0.001), the largest effect size yet reported in a West African population. MTHFR C677T heterozygosity showed a modest risk elevation (OR = 1.63, p = 0.04). Combined IRF6 risk genotype and absent periconceptional folate supplementation showed multiplicative interaction (OR = 4.87, p < 0.001). Family history of CLP was present in 18.2 percent of cases. The original genetic findings provide the first characterisation of CLP genetic risk variants in Nigerian populations and recommend genetic counselling service integration at cleft treatment centres and periconceptional folate supplementation advocacy. Keywords: cleft lip and palate, genetic epidemiology, IRF6, Nigeria, craniofacial genetics