Genetics of Congenital Tooth Agenesis

Abstract

Abstract 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‐linked 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.