Epigenetic Connections in Malocclusion.

Malocclusion arises from complex interactions among genetic, environmental, and developmental factors. While genetic contributions are well established, epigenetic mechanisms, including DNA methylation, histone modifications, non-coding RNAs, and RNA chemical modifications, have emerged as plausible regulators of craniofacial growth and dentoalveolar remodeling. This structured narrative review critically evaluates current evidence on the role of epigenetic regulation in the development of malocclusion and in orthodontic tooth movement. Most available data derive from in vitro studies, animal models, and investigations of related craniofacial processes rather than from direct analyses of defined malocclusion phenotypes in humans. Consequently, the evidence base is largely indirect and heterogeneous. To address this limitation, we applied a qualitative appraisal framework that considered study design, methodological rigor, and the directness of the evidence. Experimental findings indicate that epigenetic mechanisms are dynamically regulated by mechanical forces and may influence osteogenesis, chondrogenesis, periodontal remodeling, and individual variability in orthodontic response. However, robust causal studies directly linking specific epigenetic modifications to malocclusion phenotypes remain lacking. Although biological plausibility is strong, a substantial gap persists between mechanistic insights and clinical translation. At present, the clinical utility of epigenetic markers in orthodontic diagnosis, treatment strategy, or prognosis remains limited. Future research should prioritize well-designed longitudinal human studies integrating epigenetic profiling with clearly defined malocclusion phenotypes to establish causal relationships and enable clinically relevant applications.