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

Abstract

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.

Palatal rugae morphology is associated with variation in tooth number

“…We also undertook subgroup analysis of rugae pattern in relation to commonly described patterns of nonsyndromic tooth agenesis. In particular, we subdivided subjects into subgroups (SG1-3) of individuals with absent premolar teeth (MSX1, WNT10A) (SG1), permanent maxillary lateral incisor teeth (EDA, EDAR) (SG2) and those with tooth agenesis patterns involving absent permanent molar teeth (PAX9, AXIN2) (SG3) 41 .…”

“…It can be seen that mandibular second premolars were the most commonly absent tooth followed by maxillary lateral incisors and maxillary second premolars. We did undertake a limited subgroup analysis of rugae number and pattern in association with common patterns of tooth agenesis described in the literature in association with single gene mutations 41 and identified by phenotype within the sample. We found some associations between patterns of tooth agenesis and rugae number; however, without definitive mutational analysis it is difficult to draw any significant conclusions from these data.…”

Elements of morphology: Standard terminology for the teeth and classifying genetic dental disorders

“…The terms oligodontia and hypodontia have been used interchangeably in literature, but these define two different clinical entities if considering the number of missing teeth. Maxillary lateral incisor and second premolar are more commonly part of oligodontia (Fournier et al, ), maxillary second premolars, mandibular incisor, and maxillary and mandibular first premolars, and second molars are less frequently absent. Canines, maxillary central incisor, and first molars are the more conserved teeth.…”

Two novel mutations in MSX1 causing oligodontia

“…Among those genes, NSTA is mostly associated with mutations in PAX9, MSX1, WNT10A, AXIN2 and EDA [28][29][30]. Therefore, in this study, we searched for mutations in the above five genes in two unrelated individuals with non-syndromic oligodontia.…”