• PAX9
• MSX1
• tooth agenesis
• hypodontia

Tooth agenesis is a clinically heterogeneous disorder affecting various teeth at different rates, and is strongly influenced by ethnicity.^1,2 Evidence confirms the role of genetic heterogeneity in this common dental anomaly, and alterations in two genes have been identified as causing this condition namely, MSX1 and PAX9. Interestingly, our understanding of the genetic aetiology of human tooth agenesis is still largely based on the selective agenesis of predominantly posterior teeth. Specifically, mutations in the transcription factor PAX9 were shown to be responsible for “molar oligodontia” in three independent families,^3–7 and a large deletion of PAX9 in one nuclear family led to the absence of all posterior teeth.⁸ Moreover, point mutations in the transcription factor MSX1 have been identified in families affected with selective posterior tooth agenesis predominantly involving premolars and occasionally molars.^9–12

Although recent studies of human tooth agenesis have greatly advanced our knowledge of the genetic basis of this disorder, very few studies have specifically considered the genetic aetiology of anterior tooth agenesis.^13–15 In one study, a mutation in the SHH gene was identified in association with a solitary maxillary incisor¹⁴; however, this pattern of tooth agenesis presents as a clinical variation of the holoprosencephaly syndrome. Interestingly, in certain Asian populations (including Japanese, Chinese, and Malaysian people), the incidence of non-syndromic anterior tooth agenesis has been reported to be 2%,^16,17 which contrasts with the 0.08%–0.23% occurrence rate in a white population.¹⁸ Despite the high prevalence of incisor hypodontia, there is little known about the genetic aetiology in this pattern of tooth agenesis.

Previous studies^1–7 have increased our current understanding of the biology of tooth development, specifically concerning the roles of PAX9 and MSX1. Moreover, human genetic studies have provided interesting data …