A Theoretical Framework for the Role of Epigenetics in the Developmental Origins of Malocclusion in Nigerian Children

Malocclusion has both genetic and environmental components, and the developmental origins hypothesis proposes that early life epigenetic modifications influence craniofacial morphogenesis, but this relationship has not been theorised for the specific prenatal and postnatal exposure patterns characteristic of Nigerian children. This study developed an original Developmental Origins and Epigenetics of Malocclusion Framework for Nigerian children, drawing on developmental biology, craniofacial epigenetics, and epidemiological evidence from South West and North Central Nigeria. A constructive theory-building methodology was employed, combining systematic review of developmental origins of malocclusion literature (54 publications from 2018 to 2024), analysis of existing Nigerian birth cohort data on craniofacial development, epigenetic profiling of DNA methylation at HOX gene loci in 40 children with and 40 without severe malocclusion using buccal swabs, and expert consultation with 20 orthodontists, developmental biologists, and epidemiologists. The epigenetic profiling confirmed significant methylation differences at HOXA2 and PAX9 loci in severe malocclusion cases (p < 0.05). Prenatal malnutrition markers (low birth weight, stunting) were significantly associated with anterior open bite and posterior crossbite. Exclusive breastfeeding duration showed a significant inverse association with Class II division 2 malocclusion. The original Developmental Origins Malocclusion Framework integrates prenatal nutritional epigenetics, muscular function development, and eruption sequence timing as three interactive pathways. Expert review confirmed the framework's theoretical originality. Recommendations include a prospective epigenetic-orthodontic sub-study within the National Birth Cohort of Nigeria. Keywords: developmental origins, malocclusion, epigenetics, craniofacial development, Nigerian children