Genetics of Congenital Tooth Agenesis


Tooth agenesis is the most common congenital anomaly in humans. It has variable expression and most severe forms segregate in families, which allowed for the application of strategies for gene identification. A subset of those cases is caused by mutations in PAX9, MSX1, AXIN2, EDA, EDAR, EDARADD, and WNT10A. However, the vast majority of cases of tooth agenesis is less severe and may be the result of hypomorphic genetic variations in multiple genes. Of particular interest is the association of tooth agenesis with other conditions such as cleft lip and palate and cancer. Individuals born with oral clefts have a much higher chance to have tooth agenesis outside the cleft area. Cases of tooth agenesis caused by mutations in AXIN2 can also develop colorectal cancer. These types of cases suggest the understanding of the aetiology of developmental disruptions of dental development can also impact other relevant fields of medicine.

Key Concepts:

  • Oligodontia (agenesis of six or more teeth excluding third molars) is not common in the population (0.3%).

  • Hypodontia (agenesis of less than six teeth excluding third molars) can be as common as 11% in the population.

  • Mutations in genes such as PAX9, MSX1, and AXIN2 explain just a small percentage of oligodontia cases segregating in an autosomal dominant fashion.

  • Mutations in genes such as WNT10A explain just a small percentage of hypodontia cases segregating in an autosomal dominant fashion.

  • X‚Äźlinked inheritance of isolated oligodontia can be caused by mutations in ectodermal dysplasia genes.

  • Tooth agenesis is four times more common in individuals born with oral clefts, as well as in their relatives.

  • Individuals with oligodontia caused by mutations in AXIN2 are at higher risk for colorectal cancer.

Keywords: hypodontia; oligodontia; cancer; cleft lip and palate; MSX1; PAX9; AXIN2; EDA; WNT10A, ectodermal dysplasia

Figure 1.

Deletion of only one copy of the PAX9 gene leads to oligodontia and suggests haploinsufficiency as the etiologic mechanism (Das et al., ). Note: In NKX2‐9, NK stands for Nirenberg and Kim, the authors of the first paper describing these genes in Drosophila. X indicates this is a homeobox gene. SLC25A stands for solute carrier family 25, a mitochondrial carrier. This gene is also called adenine nucleotide translocator, member 5.

Figure 2.

Schematic representation of unilateral cleft (a) and unilateral cleft with agenesis of the lateral incisor (arrow) on the opposite side of the cleft (b), also referred to as ‘unsuccessful or occult cleft’ according to Letra et al. () (i, central incisor; l, lateral incisor; c, canine; pm, pre‐molar; m, molar).



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Further Reading

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Wyszynski DF (2002) Cleft Lip and Palate. From Origin to Treatment, p. 548. New York: Oxford University Press.

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Vieira, Alexandre R(May 2012) Genetics of Congenital Tooth Agenesis. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0023576]