Tooth Agenesis


Tooth agenesis denotes a condition where teeth are missing due to a developmental failure. According to severity, this malformation can be subdivided into hypodontia, oligodontia and anodontia. With a frequency of 20–30%, tooth agenesis is the most prevalent dental dysplasia, but not all teeth are equally affected. Familial occurrence and concordance in twins indicate potential genetic causes. Thus far, mutations could be identified for the genes MSX1, PAX9 and AXIN2. All result in oligodontia. It is assumed that the defects cause haploinsufficiency, reducing the functional gene products below a critical level, which is required for normal odontogenesis. Both hypodontia and oligodontia can occur as an isolated dental malformation or in combination with defects in other organs, for example the skin and its appendages. Such syndromes can result from genetic defects affecting MSX1 and the EDA signalling pathway. In the case of isolated hypodontia, associations have been found with sequence variants of several genes.

Key Concepts:

  • Tooth agenesis is a dental malformation in which teeth are missing, because they fail to develop.

  • Tooth agenesis in humans allows inferences to be drawn regarding the control of odontogenesis, when phenotypes and genotypes are related to experimental findings obtained from mice.

  • Mutations in human genes regulating early stages of tooth formation cause agenesis of multiple teeth, that is, oligodontia.

  • Defects of genes important for early odontogenesis probably result in haploinsufficiency and lead to a disruption of dental development, because the quantity of functional gene products is reduced below a critical level required for normal tooth formation.

  • Not all teeth are equally susceptible to a reduction in odontogenic potential.

  • Tooth agenesis can occur in a syndromic form, that is, in combination with defects in other organs and tissue, for example the skin and its appendages.

  • DNA sequence variants, which have less severe consequences for gene products are also likely to contribute to mild forms of tooth agenesis, where only a few teeth are congenitally absent.

Keywords: tooth agenesis; hypodontia; oligodontia; PAX9; MSX1; AXIN2; haploinsufficiency; syndromes; odontogenesis

Figure 1.

Panoramic radiographs of two examples of tooth agenesis. (a) Hypodontia with congenital absence of three of the four permanent second premolars; note the presence of all four permanent third molars. (b) Oligodontia with congenital absence of all four permanent third molars, second premolars, and lateral incisors; additional missing permanent teeth are the maxillary first premolars and canines, the left maxillary second molar, and the mandibular left first premolar.



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Further Reading

Thesleff I (2006) The genetic basis of tooth development and dental defects. American Journal of Medical Genetics Part A 140(23): 2530–2535.

Web Links

Gene Expression in Tooth http://bite‐

Online Mendelian Inheritance in Man (OMIM) http://www.ncbi.

Entries: 119300 (van der Woude syndrome), 192430 (velocardiofacial syndrome), 180500 (Axenfeld‐Rieger syndrome type 1), 117550 (Sotos syndrome), 189500 (Witkop syndrome), 305100, 300291, 224900 (ectodermal dysplasia), 142983 (MSX1), 167416 (PAX9), 604025 (AXIN2), 607199 (IRF6), 602054 (TBX1), 601542 (PITX2), 606681 (NSD1) 300451 (EDA), 604095 (EDAR), 606603 (EDARRAD), 300248 (IKBKG), 190170 (TGFA), 136350 (FGFR1), 120353 (MMP1), 604629 (MMP20)

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Luder, Hans Ulrich, and Mitsiadis, Thimios A(Feb 2012) Tooth Agenesis. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0005990.pub2]