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The aim of this review is to highlight some key recent developments in studies of tooth number, size and shape that are providing better insights into the roles of genetic, environmental and epigenetic factors in the process of dental development. Advances in molecular genetics are helping to clarify how epigenetic factors influence the spatial and temporal regulation of the complex processes involved in odontogenesis. At the phenotypic level, the development of sophisticated systems for image analysis is enabling new dental phenotypes to be defined. The 2D and 3D data that are generated by these imaging systems can then be analysed with mathematical approaches, such as geometric morphometric analysis. By gathering phenotypic data and DNA from twins, it is now possible to use 'genome-wide' association studies and the monozygotic co-twin design to identify important genes in odontogenesis and also to clarify how epigenetic and environmental factors can affect this process. Given that many of the common dental anomalies affecting the human dentition are interrelated, apparently reflecting pleiotropic genetic effects, the discoveries and new directions described in this paper should have important implications for clinical dental practice in the future.

This paper reviews the concept of morphogenetic fields within the dentition that was first proposed by Butler (Butler PM. Studies of the mammalian dentition. Differentiation of the post-canine dentition. Proc Zool Soc Lond B 1939;109:1-36), then adapted for the human dentition by Dahlberg (Dahlberg AA. The changing dentition of man. J Am Dent Assoc 1945;32:676-90; Dahlberg AA. The dentition of the American Indian. In: Laughlin WS, editor. The Physical Anthropology of the American Indian. New York: Viking Fund Inc.; 1951. p. 138-76). The clone theory of dental development, proposed by Osborn (Osborn JW. Morphogenetic gradients: fields versus clones. In: Butler PM, Joysey KA, editors Development, function and evolution of teeth. London: Academic Press, 1978. p. 171-201), is then considered before these two important concepts are interpreted in the light of recent findings from molecular, cellular, genetic and theoretical and anthropological investigation. Sharpe (Sharpe PT. Homeobox genes and orofacial development. Connect Tissue Res 1995;32:17-25) put forward the concept of an odontogenic homeobox code to explain how different tooth classes are initiated in different parts of the oral cavity in response to molecular cues and the expression of specific groups of homeobox genes. Recently, Mitsiadis and Smith (Mitsiadis TA, Smith MM. How do genes make teeth to order through development? J Exp Zool (Mol Dev Evol) 2006; 306B:177-82.) proposed that the field, clone and homeobox code models could all be incorporated into a single model to explain dental patterning. We agree that these three models should be viewed as complementary rather than contradictory and propose that this unifying view can be extended into the clinical setting using findings on dental patterning in individuals with missing and extra teeth. The proposals are compatible with the unifying aetiological model developed by Brook (Brook AH. A unifying aetiological explanation for anomalies of tooth number and size. Archs Oral Biol 1984;29:373-78) based on human epidemiological and clinical findings. Indeed, this new synthesis can provide a sound foundation for clinical diagnosis, counselling and management of patients with various anomalies of dental development as well as suggesting hypotheses for future studies.

With diagnostic and therapeutic advances, over 80% of children diagnosed with cancer become long-term survivors. As the number of childhood cancer survivors (CCS) continues to increase, dental practitioners become more likely to have CCS among their patients. CCS may develop late complications from damage caused by their cancer treatment to endocrine, cardiovascular, musculoskeletal, and other organ systems. These complications may surface decades after the completion of treatment. Adverse outcomes of childhood cancer treatment frequently involve oral and craniofacial structures including the dentition. Tooth development, salivary gland function, craniofacial growth, and temporomandibular joint function may be disturbed, increasing oral health risks in these individuals. Moreover, CCS are at risk of developing subsequent malignancies, which may manifest in or near the oral cavity. It is important that dental practitioners are aware of the childhood cancer history of their patients and have knowledge of potential late complications. Therefore, this narrative review aims to inform dental practitioners of late oral complications of cancer treatment modalities commonly used in pediatric oncology. Furthermore, selected common non-oral late sequelae of cancer therapy that could have an impact on oral health and on delivering dental care will be discussed. [ABSTRACT FROM AUTHOR]

Background and objective The genetic basis of dentoalveolar characteristics has been investigated by several studies, however, the findings are equivocal. The objective of this systematic review and meta-analysis was to evaluate the heritability of dental arches and occlusal parameters in different stages of human dentition. Search methods Electronic databases PubMed, Embase, Scopus, Web of Science, and Dentistry and Oral Science Source were searched up to August 2023 without the restriction of language or publication date. Selection criteria Empirical studies investigating the heritability of dentoalveolar parameters among twins and siblings were included in the review. Data collection and analysis Study selection, data extraction, and risk of bias assessment were performed independently and in duplicate by two authors and a third author resolved conflicts if needed. Joanna Briggs Institute's critical appraisal tool was used to evaluate the risk of bias among studies and the certainty of evidence was assessed using the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) criteria. Results Twenty-eight studies were included in the systematic review, of which 15 studies reporting heritability coefficients in the permanent dentition stages were deemed suitable for the meta-analysis. Random-effects meta-analyses showed high heritability estimates for maxillary intermolar width (0.52), maxillary intercanine width (0.54), mandibular intermolar width (0.55), mandibular intercanine width (0.55), maxillary arch length (0.76), mandibular arch length (0.57), and palatal depth (0.56). The heritability estimates for the occlusal parameters varied considerably, with relatively moderate values for crossbite (0.46) and overbite (0.44) and low values for buccal segment relationship (0.32), overjet (0.22), and rotation and displacement of teeth (0.16). However, the certainty of evidence for most of the outcomes was low according to the GRADE criteria. Conclusions Based on the available evidence, it can be concluded that the dental arch dimensions have a high heritability while the occlusal parameters demonstrate a moderate to low heritability. Registration PROSPERO (CRD42022358442). [ABSTRACT FROM AUTHOR]

The aims of this study are to determine the oral health status of a rare sample of 19th-century migrant settlers to South Australia, how oral conditions may have influenced their general health, and how the oral health of this group compares with contemporaneous samples in Australia, New Zealand, and Britain. Dentitions of 18 adults and 22 subadults were investigated using non-destructive methods (micro-CT, macroscopic, radiographic). Extensive carious lesions were identified in seventeen adults and four subadults, and from this group one subadult and sixteen adults had antemortem tooth loss. Sixteen adults showed evidence of periodontal disease. Enamel hypoplastic (EH) defects were identified in fourteen adults and nine subadults. Many individuals with dental defects also had skeletal signs of comorbidities. South Australian individuals had the same percentage of carious lesions as the British sample (53%), more than other historic Australian samples, but less than a contemporary New Zealand sample. Over 50% of individuals from all the historic cemeteries had EH defects, suggesting systemic health insults during dental development were common during the 19th century. The overall oral health of the South Australian settlers was poor but, in some categories, (tooth wear, periapical abscess, periodontal disease), better than the other historic samples. [ABSTRACT FROM AUTHOR]

The aim of this study is to investigate whether the genetic, epigenetic and environmental factors that give rise to supernumeraries in the maxillary incisor region and larger dimensions of the adjacent maxillary incisors are also associated with variations in the morphology of the mandibular incisors. If so, this would contribute to understanding the distribution and interactions of factors during dental development and how these can be modelled. The sample consisted of 34 patients with supernumerary teeth in the maxillary anterior region, matched for gender, age and White Caucasian ethnicity with 34 control subjects. The average ages of the supernumerary and control groups were 12.8 and 12.2 years, respectively. Study models of all subjects were constructed and imaged using a previously validated system. Using custom software, each of the mandibular incisor teeth were measured to obtain 17 parameters from the labial view and 17 from the occlusal view. Principal component analysis (PCA) was used to summarize the measurements into a smaller set representing distinct features of the clinical crowns, followed by a comparison between the supernumerary and control groups using 2-way ANOVA. Seven factors of tooth size of the mandibular central incisors and six factors of the mandibular lateral incisors were identified as major features of the clinical crowns. All parameters of both mandibular incisors were greater in the supernumerary group than in the control, with three of these, located in the incisal and cervical regions of the mandibular lateral incisors, being statistically significantly larger. The findings of this study indicate that the aetiological factors associated with supernumerary teeth in the maxillary anterior region also affect tooth crown dimensions of mandibular incisors. This new evidence enhances several models of the interactions of genetic, epigenetic and environmental components of dental development and supports a multi-model approach to increase understanding of this process and its variations. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to investigate size and shape variation of human premolars between Indigenous Australians and Australians of European ancestry, and to assess whether sex and ancestry could be differentiated between these groups using 3D geometric morphometrics. Materials and Methods: Seventy dental casts from each group, equally subdivided by sex, were scanned using a structured-light scanner. The 3D meshes of upper and lower premolars were processed using geometric morphometric methods. Seventy-two landmarks were recorded for upper premolars and 50 landmarks for lower premolars. For each tooth type, two-way ANOVA was used to assess group differences in centroid size. Shape variations were explored using principal component analysis and visualized using 3D morphing. Two-way Procrustes ANOVA was applied to test group differences for ancestry and sex, and a "leave-one-out" discriminant function was applied to assess group assignment. Results: Centroid size and shape did not display significant difference between the sexes. Centroid size was larger in Indigenous Australians for upper premolars and lower second premolars compared to the Australians of European ancestry. Significant shape variation was noted between the two ancestral groups for upper premolars and the lower first premolar. Correct group assignment of individual teeth to their ancestral groups ranged between 80.0 and 92.8% for upper premolars and 60.0 and 75.7% for lower premolars. Discussion: Our findings provide evidence of significant size and shape variation in human premolars between the two ancestral groups. High classification rates based on shape analysis of upper premolars highlight potential application of geometric morphometrics in anthropological, bioarcheological and forensic contexts. [ABSTRACT FROM AUTHOR]

The Craniofacial Biology Research Group in the School of Dentistry at The University of Adelaide is entering an exciting new phase of its studies of dental development and oral health in twins and their families. Studies of the teeth and faces of Australian twins have been continuing for nearly 30 years, with three major cohorts of twins recruited over that time, and currently we are working with twins aged 2 years old to adults. Cross-sectional data and records relating to teeth and faces of twins are available for around 300 pairs of teenage twins, as well as longitudinal data for 300 pairs of twins examined at three different stages of development, once with primary teeth, once at the mixed dentition stage, and then again when the permanent teeth had emerged. The third cohort of twins comprises over 600 pairs of twins recruited at around birth, together with other family members. The emphasis in this third group of twins has been to record the timing of emergence of the primary teeth and also to sample saliva and dental plaque to establish the timing of colonization of decay-forming bacteria in the mouth. Analyses have confirmed that genetic factors strongly influence variation in timing of primary tooth emergence. The research team is now beginning to carry out clinical examinations of the twins to see whether those who become colonized earlier with decay-forming bacteria develop dental decay at an earlier age. By making comparisons within and between monozygotic (MZ) and dizygotic (DZ) twin pairs and applying modern molecular approaches, we are now teasing out how genetic, epigenetic, and environmental factors interact to influence dental development and also oral health. [ABSTRACT FROM AUTHOR]

Two metaphors are presented to highlight concepts that could lead to a paradigm shift in dental studies of twins. The first, derived from the Song of Solomon in the Bible, refers to teeth as being twins. This viewpoint emphasises that each tooth should be viewed as a paired structure, not only with its antimere (within the same arch) but also with its isomer (in the opposing arch). The other metaphor provided by Waddington in 1957 is visual and involves 'an epigenetic landscape' that represents the processes of decision-making by cells during development. It likens the different stages of cellular decision-making to a ball rolling down an undulating landscape of interconnecting hills and valleys. This viewpoint helps to explain how distinct differences in dental phenotypes may arise both within and between monozygotic (MZ) co-twins due to relatively minor temporospatial effects during development. Measurements of maximum mesiodistal diameters of teeth in a pair of MZ twins, using calipers and also cllls2D and 3D imaging systems, have demonstrated that differences in dental crown size occur between antimeric pairs and between corresponding teeth of MZ co-twins. By defining new dental phenotypes that provide more comprehensive descriptions of tooth size and shape, and by drawing on the metaphors described, we are confident of providing new insights into the reasons for observed similarities and differences within, and between, the dentitions of twins. Our approaches will focus on multivariate analyses that take into account the paired arrangement of teeth and also explore epigenetic, as well as genetic and environmental, sources of variation. [ABSTRACT FROM AUTHOR]

This study investigated hypoplastic enamel defects in a well-defined sample of Romano–Britons from the 3rd to the 5th century AD and compared the findings with a modern British sample investigated by the same authors. All 178 excavated skulls with intact dentitions were examined for hypoplastic defects using the Federation Dentaire International (FDI) Developmental Defects of Enamel Index criteria. Histopathological and microradiographic sections were prepared of 5 teeth. Hypoplastic defects were found in the teeth of 37% of skulls, with 25% having 4 or more teeth affected. The teeth most frequently involved were canines. Of the defects, 75% were horizontal grooves, 12.7% were pitting, and 7.1% were areas of missing enamel. The location of defects was 82% buccal, 16.5% lingual, and 1.2% occlusal. The reproducibility of diagnosis was 84%. Microscopic and microradiographic investigations showed areas of hypomineralization of enamel and wide zones of interglobular dentine related to the hypoplastic grooves. There was higher frequency, different morphology, and greater severity of hypoplastic enamel defects compared with the modern British sample. The defects may be related to repeated environmental stresses between the ages of 2 and 6 yr. Identified environmental stresses in these Romano–Britons, including high lead ingestion, poor nutrition, and recurrent infections, may be important etiological factors for the enamel defects. [ABSTRACT FROM AUTHOR]

The associations seen clinically between variations in tooth number, size and shape reflect the repetitive genetic interactions occurring between the epithelium and mesenchyme during the initiation and morphogenetic stages of dental development. The aim of this study was to investigate this relationship further by comparing multiple crown parameters, including cusp numbers, between patients with mild hypodontia and controls. Digital images of dental casts of the permanent dentition from 28 Romanian subjects with mild hypodontia and 28 controls were used. Measurements of the vestibular and occlusal surfaces were performed using a 2D image analysis method. Seven dimensions were measured (mesio-distal, occluso-gingival, bucco-lingual, vestibular perimeter, vestibular area, occlusal perimeter and occlusal area) and cusps on premolars and first molars were counted. Multivariate analysis of variance was performed using SPSS V17 software. The results showed teeth in the hypodontia group were smaller than those of controls, with many measurements being significantly different (significance values varied from p=0.048 to p=0.0001). Lower first incisors and upper first premolar teeth presented the most reduced dimensions. Mesio-distal, bucco-lingual and occlusal area and perimeter dimensions were the most affected. Upper first molars presented the Carabelli trait in significantly less subjects in the hypodontia group than in controls. This variation was accompanied by a difference in tooth height. Lower premolars showed reduced cusp numbers in hypodontia subjects, accompanied by variation in tooth width or depth. In conclusion, this study demonstrated differences in multiple parameters of crown size and shape in patients with mild hypodontia compared to controls. The degree of these differences varied between different tooth types and dimensions. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to investigate the prevalence of selected dental variations in association with infraocclusion, as well as determining the effects of infraocclusion on dental development and tooth size, in singletons and twins. Design Two samples were analysed. The first sample comprised 1454 panoramic radiographs of singleton boys and girls aged 8–11 years. The second sample comprised dental models of 202 pairs of monozygotic and dizygotic twins aged 8–11 years. Adobe Photoshop CS5 was used to construct reference lines and measure the extent of infraocclusion (in mm) of primary molars on the panoramic radiographs and on 2D images obtained from the dental models. The panoramic radiographs were examined for the presence of selected dental variations and to assess dental development following the Demirjian and Willems systems. The twins’ dental models were measured to assess mesiodistal crown widths. Results In the singleton sample there was a significant association of canines in an altered position during eruption and the lateral incisor complex (agenesis and/or small tooth size) with infraocclusion ( P < 0.001), but there was no significant association between infraocclusion and agenesis of premolars. Dental age assessment revealed that dental development was delayed in individuals with infraocclusion compared to controls. The primary mandibular canines were significantly smaller in size in the infraoccluded group ( P < 0.05). Conclusion The presence of other dental variations in association with infraocclusion, as well as delayed dental development and reduced tooth size, suggests the presence of a pleiotropic effect. The underlying aetiological factors may be genetic and/or epigenetic. [ABSTRACT FROM AUTHOR]

Abstract: Aims: In studying aetiological interactions of genetic, epigenetic and environmental factors in normal and abnormal developments of the dentition, methods of measurement have often been limited to maximum mesio-distal and bucco-lingual crown diameters, obtained with hand-held calipers. While this approach has led to many important findings, there are potentially many other informative measurements that can be made to describe dental crown morphology. Advances in digital imaging and computer technology now offer the opportunity to define and measure new dental phenotypes in 3-D that have the potential to provide better anatomical discrimination and clearer insights into the underlying biological processes in dental development. Over recent years, image analysis in 2-D has proved to be a valuable addition to hand-measurement methods but a reliable and rapid 3-D method would increase greatly the morphological information obtainable from natural teeth and dental models. Additional measurements such as crown heights, surface contours, actual surface perimeters and areas, and tooth volumes would maximise our ability to discriminate between samples and to explore more deeply genetic and environmental contributions to observed variation. The research objectives were to investigate the limitations of existing methodologies and to develop and validate new methods for obtaining true 3-D measurements, including curvatures and volumes, in order to enhance discrimination to allow increased differentiation in studies of dental morphology and development. The validity of a new methodology for the 3-D measurement of teeth is compared against an established 2-D system. The intra- and inter-observer reliability of some additional measurements, made possible with a 3-D approach, are also tested. Methods and results: From each of 20 study models, the permanent upper right lateral and upper left central incisors were separated and imaged independently by two operators using 2-D image analysis and a 3-D image analysis system. The mesio-distal (MD), labio-lingual (LL) and inciso-gingival (IG) dimensions were recorded using our 2-D system and the same projected variables were also recorded using a newly developed 3-D system for comparison. Values of Pearson''s correlation coefficient between measurements obtained using the two techniques were significant at the 0.01 probability level for variables mesio-distal and incisal-gingival with labio-lingual significant at the 0.05 level for the upper left side only, confirming their comparability. For both 2-D and 3-D systems the intra- and inter-operator reliability was substantial or excellent for variables mesio-distal, labio-lingual, incisal-gingival actual and projected and actual surface area. The reliability was good for inter-operator reliability measurement of the labio-lingual dimension using 3-D. Conclusions: We have developed a new 3-D laser scanning system that enables additional dental phenotypes to be defined. It has been validated against an established 2-D system and shown to provide measurements with excellent reliability, both within and between operators. This new approach provides exciting possibilities for exploring normal and abnormal variations in dental morphology and development applicable to research on genetic and environmental factors. [Copyright &y& Elsevier]

Abstract: Utilising data derived from twins and their families, different approaches can be applied to study genetic and environmental influences on human dental variation. The different methods have advantages and limitations and special features of the twinning process are important to consider. Model-fitting approaches have shown that different combinations of additive genetic variance (A), non-additive genetic variance (D), common environmental variance (C), and unique environmental variance (E) contribute to phenotypic variation within the dentition, reflecting different ontogenetic and phylogenetic influences. Epigenetic factors are also proposed as important in explaining differences in the dentitions of monozygotic co-twins. Heritability estimates are high for most tooth size variables, for Carabelli trait and for dental arch dimensions, moderate for intercuspal distances, and low for some occlusal traits. In addition to estimating the contributions of unmeasured genetic and environmental influences to phenotypic variation, structural equation models can also be used to test the effects of measured genetic and environmental factors. Whole-genome linkage analysis, association analysis of putative candidate genes, and whole genome association approaches, now offer exciting opportunities to locate key genes involved in human dental development. [Copyright &y& Elsevier]