Genetic basis of tooth agenesis

Abstract

Tooth agenesis or hypodontia, failure to develop all normally developing teeth, is one of the most common developmental anomalies in man. Common forms, including third molar agenesis and hypodontia of one or more of the incisors and premolars, constitute the great majority of cases. They typically affect those teeth that develop latest in each tooth class and these teeth are also most commonly affected in more severe and rare types of tooth agenesis. Specific vulnerability of the last developing teeth suggests that agenesis reflects quantitative defects during dental development. So far molecular genetics has revealed the genetic background of only rare forms of tooth agenesis. Mutations in MSX1, PAX9, AXIN2 and EDA have been identified in familial severe agenesis (oligodontia) and mutations in many other genes have been identified in syndromes in which tooth agenesis is a regular feature. Heterozygous loss of function mutations in many genes reduce the gene dose, whereas e.g. in hypohidrotic ectodermal dysplasia (EDA) the complete inactivation of the partially redundant signaling pathway reduces the signaling centers. Although these mechanisms involve quantitative disturbances, the phenotypes associated with mutations in different genes indicate that in addition to an overall reduction of odontogenic potential, tooth class-specific and more complex mechanisms are also involved. Although several of the genes so far identified in rare forms of tooth agenesis are being studied as candidate genes of common third molar agenesis and incisor and premolar hypodontia, it is plausible that novel genes that contribute to these phenotypes will also become identified.