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.

MSX1 mutations and associated disease phenotypes: genotype-phenotype relations

“…Previous studies have mainly focused on tooth agenesis, associating the MSX1 variants to the type and number of missing teeth, and it is generally concluded that the most frequently missing teeth in case of MSX1 variants are the second premolars. [13][14][15] In a previous study we identified a novel MSX1 mutation causing tooth agenesis with cleft lip, further confirming that different MSX1 mutations may cause different phenotypes. 16 This review reveals a strong correlation between observed phenotypes and the location in the MSX1 protein structure of the disease causing mutations.…”

Variability in dentofacial phenotypes in four families with WNT10A mutations

“…13 To identify the present/absent teeth, the Fédération Dentaire Internationale tooth numbering system is used.). Both intra-and extra-oral two-dimensional (2D) photographs as well as facial 3D stereophotogrammetry images were made.…”

“…The proband was 19 years old at the time of inclusion (patient B II-3) with severe TA missing 12 permanent teeth (17,13,11,21,23,24,27,32,33,34,35,37,42,43,44,47). The upper anterior teeth show a conical aspect and the permanent upper first molars are hypoplastic.…”

“…Clinical examination proband. In her permanent dentition, she has severe TA of 23 teeth (17, 15, 14 (16,13,23, 33 and 46), two of which have a conical shape and one being hypoplastic. Although her mandible is also retruded, leading to a convex profile, the dished-in appearance is again the most catching feature in her facial profile.…”

Mutation of KREMEN1, a modulator of Wnt signaling, is responsible for ectodermal dysplasia including oligodontia in Palestinian families

“…1 Oligodontia appears in approximately 1 in 1000 persons and may be isolated or syndromic. Genes responsible for non-syndromic oligodontia, which is generally dominantly inherited, include MSX1 (MIM 142983), PAX9 (MIM 167416), WNT10A (MIM 606268), EDA1 (MIM 300451), and LRP6.…”