Dental agenesis: genetic and clinical perspectives

Abstract

Dental agenesis is the most common developmental anomaly in humans and is frequently associated with several other oral abnormalities. Whereas the incidence of missing teeth may vary considerably depending on dentition, gender, and demographic or geographic profiles, distinct patterns of agenesis have been detected in the permanent dentition. These frequently involve the last teeth of a class to develop (I2, P2, M3) suggesting a possible link with evolutionary trends. Hypodontia can either occur as an isolated condition (non-syndromic hypodontia) involving one (80% of cases), a few (less than 10%) or many teeth (less than 1%), or can be associated with a systemic condition or syndrome (syndromic hypodontia), essentially reflecting the genetically and phenotypically heterogeneity of the condition. Based on our present knowledge of genes and transcription factors that are involved in tooth development, it is assumed that different phenotypic forms are caused by different genes involving different interacting molecular pathways, providing an explanation not only for the wide variety in agenesis patterns but also for associations of dental agenesis with other oral anomalies. At present, the list of genes involved in human non-syndromic hypodontia includes not only those encoding a signaling molecule (TGFA) and transcription factors (MSX1 and PAX9) that play critical roles during early craniofacial development, but also genes coding for a protein involved in canonical Wnt signaling (AXIN2), and a transmembrane receptor of fibroblast growth factors (FGFR1). Our objective was to review the current literature on the molecular mechanisms that are responsible for selective dental agenesis in humans and to present a detailed overview of syndromes with hypodontia and their causative genes. These new perspectives and future challenges in the field of identification of possible candidate genes involved in dental agenesis are discussed.

Variability in dentofacial phenotypes in four families with WNT10A mutations

“…9,24 Moreover, the predisposition of 'second teeth' agenesis pattern -upper second incisors, upper and lower second premolars and upper and lower second molars -is present in most patients which is in accordance with the findings described by Polder et al in 2004. 1 Profile analysis was performed on both intra-and extra oral 2D photographs as well as facial 3D stereophotogrammetric images.…”

“…The proband was 19 years old at the time of inclusion (patient B II-3) with severe TA missing 12 permanent teeth (17,13,11,21,23,24,27,32,33,34,35,37,42,43,44,47). The upper anterior teeth show a conical aspect and the permanent upper first molars are hypoplastic.…”

Mutation of KREMEN1, a modulator of Wnt signaling, is responsible for ectodermal dysplasia including oligodontia in Palestinian families

“…Homozygosity mapping was carried out using the AffyMetrix 250 K Nsp SNP microarray as previously described. 6 Exome sequencing was carried out on an Illumina HiSeq2500 (Illumina, Inc., San Diego, CA, USA), as previously described, 5,7 with updated details in Supplementary Methods. Consequences of DNA changes at the RNA level were confirmed by Sanger sequencing of cDNA generated from RNA extracted from white cells of participants.…”

“…Syndromic oligodontia appears as a feature of multiple forms of ectodermal dysplasias, for many of which the responsible genes have been identified. 5 Even given this extensive body of knowledge, new forms of oligodontia continue to appear in the course of dental practice. The present study was motivated by the appearance of severe oligodontia, accompanied by anomalies of hair and skin, first in eight members of two extended kindreds, then in two additional families from the same neighborhood, during the practice of dentistry by one of us (YAI) in Hebron, Palestine.…”

Dentistry and Molecular Biology: A Promising Field for Tooth Agenesis Management

“…dency toward the increased frequency of tooth agenesis (Vastardis 2000;De Coster et al 2009). In either case, a deeper analysis of the gene networks underlying tooth agenesis is critical.…”