Genetic Insights into Oligodontia: A Comprehensive Review of Mutations in Key Genes and Their Implications for Tooth Development

Abstract : Introduction: Tooth agenesis is one of the most frequent congenital abnormalities found in the maxillofacial region. Oligodontia, a severe form of tooth agenesis, occurs as an isolated anomaly or as a syndromic feature. Objectives: To identify the molecular genetic etiology of multiple missing permanent teeth (oligodontia). Discussion: Disruptions in tooth development arise from mutations in genes like WNT10A and PAX9, where PAX9 plays a crucial role in dental epithelial cell differentiation. Additional genes, such as MSX1, AXIN2, EDA, EDAR, and EDARADD, play diverse roles in tooth agenesis. The WNT pathway, particularly the WNT/β-catenin signaling, is crucial in tooth development. Mutations in LRP6 compromise the activation of this pathway, indicating its functional significance in tooth development. Biallelic variants in POLR3GL have been associated with oligodontia, expanding the spectrum of POLR3-related disorders. Disruption of Pol III function may affect the transcription of essential RNAs involved in tooth development. Conclusions: Oligodontia is a genetically heterogeneous condition with a complex genetic basis involving multiple genes and pathways. Molecular analysis and genetic testing are essential for accurate diagnosis and management, contributing to our evolving understanding of the genetic causes of oligodontia.