Comparison of the pattern of agenesis in the primary and permanent dentitions in a population characterized by agenesis in the primary dentition

The first aim of this study was to collect a large sample of radiographs from children with congenitally missing teeth (CMT) in the primary dentition and to analyse the local relationship between agenesis of a primary tooth and the presence/absence of its permanent successor. The second aim was to compare, in the same sample, the pattern of agenesis in the primary dentition with the developmental pattern seen in the permanent dentition. 124 dentists from 72 municipalities contributed to the investigation of a total of 213 children. The dentists were asked to lend existing radiographic material from patients with agenesis in the primary dentition. The analysis of the local occurrence of agenesis showed that agenesis of a primary incisor was often but not always followed by agenesis of the succedaneous tooth. In the molar region, agenesis of a primary tooth was in all cases but one followed by agenesis of the succedaneous tooth. Comparison of the pattern of CMT in the primary dentition with the pattern of tooth presence/absence in the permanent dentition in a group of 33 patients, for whom complete radiographic material was available showed that agenesis always occurred in the permanent dentition and that the pattern of agenesis in the permanent dentition differed from that in the primary dentition. Incisors were most frequently missing in the primary dentition and premolars in the permanent dentition. The number of congenitally missing teeth was substantially larger in the permanent dentition than in the primary dentition. Also, permanent teeth that are very rarely congenitally missing were missing in this sample, characterized by the occurrence of agenesis in the primary dentition.     

The genetic basis of tooth agenesis: basic concepts and genes involved

Tooth agenesis is the most prevalent craniofacial congenital malformation in humans. While tooth agenesis may be associated with several syndromes, non-syndromic hypodontia refers to the congenital absence of a few teeth in the absence of any other deformity. Recent advances in molecular genetics have made it possible to identify the exact genes responsible for the development of teeth and trace the mutations that cause hypodontia. This paper reviews the literature regarding the genetic basis of non-syndromic tooth agenesis, methods used to study it, and the genes that have been definitively implicated in the agenesis of human dentition.     

Taurodontism in Brazilian patients with tooth agenesis and first and second-degree relatives: a case-control study

AimAn association between tooth agenesis and taurodontism has been suggested. To verify if tooth agenesis and taurodontism are associated within families and specific patterns of tooth agenesis, this study aims to compare the frequency of taurodontism in patients with nonsyndromic familial tooth agenesis, their first and second-degree relatives with complete permanent dentition and a control group of unrelated healthy individuals with complete permanent dentition.Materials and methodsPanoramic radiographs of patients with nonsyndromic familial tooth agenesis, their first and second-degree relatives and a control group of individuals with complete permanent dentition were examined. Taurodontism was assessed on permanent mandibular first molars. The difference in the frequency of taurodontism among the studied groups was tested with Fisher's Exact Test.ResultsSeventeen families with nonsyndromic familial tooth agenesis were studied. The frequency of taurodontism was 29% in patients with tooth agenesis, 10.3% in their first and second degree relatives, and 6.6% in the control group. A significant statistical difference among the studied groups was observed (p = 0.002). Taurodontism was proportionally more frequent in patients with a higher number of absent teeth. It was mainly observed in patients from families in which the proband was diagnosed with oligodontia.ConclusionsTaurodontism is more frequent in nonsyndromic familial tooth agenesis. Individuals in families with second premolar and molar oligodontia are more likely to have taurodontism, even the individuals with complete dentition. This association could define a subphenotype for future genetic studies of dental development.     

Novel mutation in the paired box sequence of PAX9 gene in a sporadic form of oligodontia

Tooth development is regulated through a series of reciprocal interactions between the dental epithelium and mesenchyme and requires protein products of a number of genes. It has been reported that selective tooth agenesis is associated with mutations in human MSX and PAX9 genes. Mutational analysis of the two genes was performed in 25 individuals with familial or sporadic form of permanent tooth agenesis. Single-stranded conformational polymorphism analysis revealed no mutations in the entire coding sequence of the MSX1 gene. In PAX9, a novel, heterozygous G151A transition in the sequence encoding the paired domain of the PAX9 protein was detected in a patient with agenesis of third molars, second premolars and incisors, but not in her parents, the remaining patients or 162 individuals with normal dentition. This is the first de novo mutation described in PAX9. Our results support the view that mutations in PAX9 could constitute a causative factor of oligodontia. We hypothesize that the G151A transition in PAX9 might be responsible for the sporadic form of tooth agenesis in this patient.     

同源异型盒基因-1与非综合征型多数牙先天性缺失

牙缺失是常见的颌面发育异常之一,在恒牙列中的发病率高达20%,而其表现程度也存在较大差异.在过去的数十年中,遗传连锁和分子生物学研究使得部分综合征和非综合征型牙缺失的基因突变得以定位.尽管作用机制尚未明了,但现已知其中所涉及的重要突变因子包括了编码转录因子的同源异型盒基因(msx)-1、双链复合蛋白基因(pax)-9和轴抑制基因(axin)-2.下面从近年来国内外有关先天性牙缺失的病例报告、致病基因分析以及分子生物学和生物化学等研究方面就msx-1基因与非综合征型牙缺失的关系进行综述.     

Estimation of tooth agenesis risks between tooth types in orthodontic patients with non-syndromic oligodontia

Oligodontia, a severe type of hypodontia generally characterized as tooth agenesis of six or more permanent teeth excluding third molars, is known to have a multifactorial etiology and the characteristics of orthodontic patients are not fully understood. The aim of the present study was to investigate the risks of tooth agenesis between tooth types of permanent dentition in orthodontic patients with non-syndromic oligodontia. Panoramic radiographs of 292 orthodontic patients (184 females and 108 males) were obtained from one university-based orthodontic clinic and 79 private orthodontic clinics in Japan. Agenesis of permanent teeth excluding third molars was evaluated. Multiple logistic regression analysis was conducted to evaluate the risk of simultaneous tooth agenesis between all tooth type combinations. Significant symmetry of tooth agenesis was observed for all tooth types. Twenty-six tooth type combinations showed a significantly increased risk of simultaneous tooth agenesis [odds ratios (ORs): 1.99⬜14.51], and 15 tooth type combinations showed a significantly decreased risk of simultaneous tooth agenesis (ORs: 0.11⬜0.56). These findings suggest early detection to establish appropriate multidisciplinary treatment planning and prediction of the risk for tooth agenesis of non-syndromic oligodontia.     

非综合征型先天缺牙致病基因和分子机制的研究进展

先天缺牙是牙齿发育过程中常见的牙数目发育异常,对患者的颌面部发育及美观和咀嚼功能产生严重的影响。根据有无伴发全身症状,先天缺牙可分为综合征型先天缺牙与非综合征型先天缺牙。近几年发现新的相关基因和新的突变位点及分子机制已成为目前非综合征型先天缺牙基因研究的主要方向。本文通过对近年来文献的回顾,对与非综合征型先天缺牙主要相关的Wnt/β-catenin信号通路、TGF-β/BMP信号通路、PAX9基因和MSX1基因、EDA/EDAR/NF-κb信号通路的分子机制以及相互调节的紧密联系进行综述,为未来先天缺牙的防治提供了新的理论基础。非综合征型先天缺牙致病基因的分子机制的研究目前甚少,对于其机制的精准探索将成为先天缺牙未来主要的研究方向之一。     

Dental agenesis patterns in Crouzon syndrome

Dental agenesis may be present in an isolated familiar manner, or occur as a part of a syndrome.To date, this clinical trait seems to have been overlooked in patients with Crouzon syndrome.The aim of the present study was to investigate dental agenesis and dental agenesis patterns in a population of persons with Crouzon syndrome in Sweden. Serial panoramic radiographs of 26 individuals with Crouzon syndrome (20 males, 6 females) were examined.Third molars were excluded from the assessment. The prevalence of agenesis for at least one tooth was 42.3%. Each affected patient was found to have up to 5 missing teeth. Upper and lower second premolars were the most frequently congenitally missing teeth. Eleven dental agenesis patterns of the entire dentition were identified, as described by the tooth agenesis code (TAC). All patterns were unique and asymmetric,with only one exception, a symmetric pattern of the maxillary and mandibular second premolars. In conclusion, persons with Crouzon syndrome were found to have a high prevalence of dental agenesis and a remarkable variability of dental agenesis patterns. It is important to be aware of this clinical situation, especially when orthodontic treatment planning for these patients is performed as early as in the mixed dentition.     

Dental agenesis patterns of permanent teeth in Apert syndrome

Dental agenesis may either occur as an isolated trait (non-syndromic) or as a component in a congenital syndrome. The aim of the present study was to identify the prevalence of dental agenesis for each type of tooth and to look for dental agenesis patterns in persons with Apert syndrome. Serial panoramic radiographs of 23 individuals (five male patients and 18 female patients) were examined. Third molars were excluded. The prevalence of agenesis for at least one tooth was 34.8%. Up to two missing teeth were found for individuals with Apert syndrome. Maxillary lateral incisors and mandibular second premolars were the most frequently missing teeth. Four different dental agenesis patterns of the entire dentition were identified by using the tooth agenesis code (TAC). Two patterns occurred more frequently, both of which were symmetrical. One involved the simultaneous absence of teeth 12 and 22, and the other showed agenesis of teeth 35 and 45. In conclusion, patients with Apert syndrome were found to exhibit a high prevalence of dental agenesis. All dental agenesis patterns in which more than one tooth was missing were symmetrical.     

The genetics of human tooth agenesis: New discoveries for understanding dental anomalies

The important role of genetics has been increasingly recognized in recent years with respect to the understanding of dental anomalies, such as tooth agenesis. The lack of any real insight into the cause of this condition has led us to use a human molecular genetics approach to identify the genes perturbing normal dental development. We are reporting a strategy that can be applied to investigate the underlying cause of human tooth agenesis. Starting with a single large family presenting a clearly recognizable and well-defined form of tooth agenesis, we have identified a defective gene that affects the formation of second premolars and third molars. With the use of "the family study" method, evidence is produced showing that other genetic defects also contribute to the wide range of phenotypic variability of tooth agenesis. Identification of genetic mutations in families with tooth agenesis or other dental anomalies will enable preclinical diagnosis and permit improved orthodontic treatment.     

The unresolved problem of the third molar: would people be better off without it?

BACKGROUND: Third molars are teeth that have little functional value and a relatively high rate of associated pain and disease. Their value as part of the dentition of modern people is dubious. TYPES OF STUDIES REVIEWED: The authors review the evolution, development, morbidity and treatment of third molars. They assess the value of third molars in the 21st century and describe the risks these teeth pose when they develop in the dentition. CONCLUSIONS: There is a mandate for the dental profession to improve health outcomes and quality of life. The prevention of third molar-related morbidity should be included in dental research efforts. The authors suggest that novel preventive methodologies be developed to alleviate the problems third molars pose. One potential methodology suggested is intentional therapeutic agenesis of this tooth. CLINICAL IMPLICATIONS: Prevention of third molar development early in life, even before tooth bud initiation, could dramatically improve health care outcomes for millions of people.     

A case–control study of the association between tooth‐development gene polymorphisms and non‐syndromic hypodontia in the Chinese Han population

Hypodontia is one of the most common anomalies of human dentition. Recent genetic studies provide information on a number of genes related to both syndromic and non‐syndromic forms of hypodontia. Fifty putative single nucleotide polymorphisms (SNPs) in 20 genes that play important roles in tooth development were selected, and a case–control study was conducted in 273 subjects with hypodontia (cases) and 200 subjects without hypodontia (controls). DNA was obtained from samples of whole blood or saliva. Genotyping was performed by matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry (MALDI‐TOF‐MS). A significant difference was observed, between subjects with non‐syndromic hypodontia and controls, in the allele and genotype frequencies of two markers [rs929387 of GLI family zinc finger 3 (GLI3) and rs11001553 of Dickkopf‐related protein 1 (DKK1)]. Similar results were observed in a subgroup analysis of test subjects (stratified by gender or missing tooth position). However, this analysis showed no significant difference in the haplotype distribution between the controls and the affected subjects. These data demonstrate an association between some SNPs in tooth development‐associated genes and sporadic non‐syndromic hypodontia in Chinese Han individuals. This information may provide further understanding of the molecular mechanisms of tooth agenesis. Furthermore, these genes can be regarded as candidates for mutation detection in individuals with tooth agenesis.     

Patterns of non-syndromic permanent tooth agenesis in a large orthodontic population

ObjectiveThe aim of this study is to explore patterns of non-syndromic permanent tooth agenesis in a large orthodontic patient group.DesignA record review was performed in various orthodontic clinics to identify white patients with non-syndromic permanent tooth agenesis, excluding 3rd molars. Four hundred and fourteen subjects fulfilled the inclusion criteria.ResultsIn the 414 subjects with tooth agenesis, approximately 70% presented 1–2 missing teeth. Symmetric agenesis patterns were often observed in the sample (by jaw, by side, or crossed quadrants), with prevalence approaching 30% for cases with contralateral tooth agenesis within a jaw. In cases with 1 or 2 missing teeth, from the total number of potential tooth agenesis patterns in the sample, a certain part was evident, limiting the variation to 27.8% (44/158). In the entire sample, both in the maxilla and the mandible a certain incisor/premolar agenesis phenotype was observed in 59.0% of cases in isolated form.ConclusionsAlthough there was variation in the tooth agenesis patterns, our findings suggest the involvement of particular genetic, epigenetic, and/or environmental factors in the formation of the entire dentition, which often lead to specific tooth agenesis phenotypes in cases where this process is disrupted.The present study provides a comprehensive categorization of orthodontic cases with tooth agenesis and can assist in planning future epidemiological and genetic studies.     

Patterns of missing teeth in a population of oligodontia patients

PURPOSE: The purpose of this study was to characterize a population of oligodontia patients and identify patterns of tooth agenesis. MATERIALS AND METHODS: A total of 116 patients with nonsyndromic oligodontia were studied, and the Tooth Agenesis Code (TAC) per quadrant was calculated. Oligodontia was defined as the congenital absence of 6 or more permanent teeth, excluding the third molars. The TAC is a unique number, consistent with a specific pattern of tooth agenesis. The authors suggest the use of an overall TAC with which the dentition throughout the mouth can be presented by a single number. Frequency analysis was used to study the prevalence of various patterns. RESULTS: There was a great diversity of TACs. In the maxilla, agenesis of both premolars and the lateral incisor or the presence of only the central incisor and first molar were the most common patterns. In the mandible, agenesis of the second premolar or both premolars occurred most frequently. CONCLUSIONS: No single pattern of agenesis occurred more than twice when the full mouth was viewed. Hence, the presentation of the dentition in oligodontia is very heterogeneous. Evaluation of treatment strategies in oligodontia patients is a methodologic challenge because homogenous, comparable subgroups of patients are not available.     

Patterning of the murine dentition by homeobox genes

Homeobox genes have been shown to be important for the regulation of pattern formation of many systems during embryogenesis. Overlapping domains of Hox gene expression in the paraxial mesoderm have been suggested to create a combinatorial code of expression (Hox code) specifying the structures of individual segments such as the vertebrae. Hox genes are not expressed in the neural crest cells contributing to tooth formation, and so a Hox code can not be involved in patterning the dentition. It has previously been proposed that other, non-Hox homeobox genes may pattern the dentition. Expression data in this paper shows that there is a pattern of overlapping domains of homeobox gene expression in facial mesenchyme prior to the initiation of tooth development. We propose that expression of these genes constitutes an odontogenic homeobox code which patterns the dentition.