Genetic factors associated with Class II division 2 malocclusion – A systematic review

Objective: To systematically review the genes that code for Class II division 2 malocclusion. Materials and Methods:A systematic search using appropriate keywords was performed in PubMed, Scopus, Web of Science, LILACS and OVID database upto 5 August 2025.Inclusion and exclusion criteria were framed to include studies that identified the genes coding for Class II division 2 malocclusion.Down and Black quality checklist was used to assess the risk of bias.Results: A total of 7120 studies were obtained after which 4 articles met the inclusion and exclusion criteria.PAX9, MSX1, FGF8, FOXL2 and ISL1 genes were associated with Class II division 2 malocclusion.In the PAX9 (rs8004560) gene, the AG genotype is more susceptible for the development of Class II division 2 malocclusion by 4 times (OR: 4.38).In the MSX1 (rs3821949) gene, the GG genotype is more susceptible for the development of Class II division 2 malocclusion.FGF8 (rs10786648, rs4919593) and FOXL2 (rs9809852) were associated with Class II division 2 features.The CC genotype in the variant of MSX1 (g.4861745), (g.4861974), (g.4861721), (g.4864876), AA genotype in (g.4861753), GG genotype in (g.4861609) were observed in Class II division 2 malocclusion.Conclusions: This systematic review showed there is conclusive evidence that PAX9, MSX1, FGF8, FOXL2 and ISL1 were associated with Class II division 2 malocclusion.Understanding the underlying mechanisms of this pathology is essential for a deeper insight into its aetiology, enabling the development of preventive measures, personalized therapeutic approaches, and more precise treatment planning strategies.Clinical Relevance: Literature evidences suggests that Class II division 2 malocclusion has a strong genetic influence in its establishment.The treatment of Class II division 2 malocclusion requires intervention at the appropriate timing thereby diagnosis plays a crucial role in the same.