Patterns of Dental Agenesis Highlight the Nature of the Causative Mutated Genes

The most common outcome of defective dental morphogenesis in human patients is dental agenesis (absence of teeth). This may affect either the primary or permanent dentition and can range from 5 or fewer missing teeth (hypodontia), 6 or more (oligodontia), to complete absence of teeth (anodontia). Both isolated and syndromic dental agenesis have been reported to be associated with a large number of mutated genes. The aim of this review was to analyze the dental phenotypes of syndromic and nonsyndromic dental agenesis linked to gene mutations. A systematic review of the literature focusing on genes (MSX1, PAX9, AXIN2, PITX2, WNT10A, NEMO, EDA, EDAR, EDARADD, GREMLIN2, LTBP3, LRP6, and SMOC2) known to be involved in dental agenesis was performed and included 101 articles. A meta-analysis was performed using the dental phenotypes of 522 patients. The total number and type of missing teeth were analyzed for each mutated gene. The percentages of missing teeth for each gene were compared to determine correlations between genotypes and phenotypes. Third molar agenesis was included in the clinical phenotype assessment. The findings show that isolated dental agenesis exists as part of a spectrum of syndromes for all the identified genes except PAX9 and that the pattern of dental agenesis can be useful in clinical diagnosis to identify (or narrow) the causative gene mutations. While third molar agenesis was the most frequent type of dental agenesis, affecting 70% of patients, it was described in only 30% of patients with EDA gene mutations. This study shows that the pattern of dental agenesis gives information about the mutated gene and could guide molecular diagnosis for geneticists.