Genetic and phenotypic heterogeneity of tooth agenesis: An update including candidate genes

Abstract

Objective

This study aims to further investigate the genetic etiology as well as the corresponding characteristics of tooth agenesis (TA). It focuses on expanding the gene spectrum and exploring genotype-phenotype correlations and potential candidate genes for TA.

Design

The narrative review approach was conducted, providing a comprehensive perspective of tooth agenesis-related literature.

Results

We describe the (candidate) causal genes of syndromic TA and nonsyndromic TA respectively. There is overlap between the gene spectrum of the two forms. Tooth phenotypes (either the number of missing teeth or the malformations) of syndromic form are more severe than that of nonsyndromic form. The phenomenon even exists among family members carried the same variant, highlighting the disorder’s complexity and the causal genes’ expression variability. Besides, the candidate genes, corresponding functional and case evidence are updated, which contributes to improve the diagnosis of TA.

Conclusions

TA is a group of complex disorder regulated by multiple genetic signaling pathways. We review the previously known and novel found genes/candidate genes related to TA, emphasizing the genetic and phenotypic heterogeneity. The enlarged spectrum is useful for further promoting the understanding of TA and early diagnosis. It is suggested that molecular diagnosis is particularly vital for early management and genetic counseling.