The genetic basis of over-retained deciduous teeth and delayed permanent tooth eruption: A systematic review

Tooth eruption is a complex biological process regulated by genetic and environmental factors. Deviations from the normal tooth eruption sequence, such as over-retained deciduous teeth (ORDT) and delayed permanent tooth eruption (DPTE), can lead to multiple complications. Although several local and systemic factors are well-established contributors, increasing evidence suggests a potential genetic contribution to tooth eruption disturbances. The aim of this systematic review was to identify genes and genetic traits potentially associated with ORDT or DPTE through systematically reviewing the literature.

Relevant literature was searched on 13 databases up to March 2025, and search criteria were formulated using the PECOS (Population, Exposure, Comparison, Outcomes, and Study design) framework and the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The eligibility criteria included case-control, cohort, and cross-sectional observational studies that examined human subjects regardless of age or sex and focused on the analysis of genes, alleles, gene variants, or other genetic factors implicated in ORDT and DPTE. The risk of bias was assessed using the Joanna Briggs Institute critical appraisal tool.

Overall, 6 studies met the inclusion criteria. Among the 3 case-control studies, 2 identified associations with RANKL (rs9594738) and COX2 (rs5275 and rs689466) polymorphisms, in which the presence of specific alleles was more frequent among individuals with persistent deciduous teeth. The third study noted that vitamin D deficiency was associated with tooth eruption disturbances, although polymorphisms in the vitamin D receptor gene (rs2228570 and rs739837) were not associated with tooth eruption disturbances. The other 2 cross-sectional studies reported links between delayed tooth eruption and variants in MMP8 (rs17099443) and the vitamin D receptor gene (VDR rs2228570), whereas 1 genome-wide association study identified 4 loci (HMGA2 rs12424086, TNP1 rs4491709, CACNA1S/TMEM9 rs2281845, and ADK rs7924176) that were associated with permanent tooth eruption, highlighting the polygenic nature of tooth eruption timing.

This review supports the contribution of genetic polymorphisms to the occurrence of ORDT and DPTE. Variants in genes involved in bone resorption, extracellular matrix remodeling, and mineral metabolism, such as RANKL, COX2, and MMP8, as well as genome-wide association study-identified loci, were repeatedly associated with eruption timing. These findings suggest that DPTE and ORDT are not solely because of environmental or local factors but may also involve genetic factors. However, more large-scale, multiethnic cohorts with standardized diagnostic criteria for ORDT and DPTE are needed to draw safe conclusions on the precise role of genetic traits.