The European Journal of Orthodontics Advance Access originally published online on December 22, 2005
The European Journal of Orthodontics 2006 28(2):145-151; doi:10.1093/ejo/cji092
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Dental transposition as a disorder of genetic origin
Departments of * Orthodontics and ** Dental Biomaterials, at Guy's King's College and St Thomas' Hospitals, London, UK
Address for correspondence Martyn Cobourne, Department of Orthodontics, Floor 22, Guy's Tower, Dental Institute at Guy's King's College and St Thomas' Hospitals, London SE1 9RT, UK, E-mail: martyn.cobourne{at}kcl.ac.uk
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Summary |
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A sample of 85 dental transpositions in 75 subjects (27 male, 48 female; mean age at diagnosis 12.25 years) involving both maxillary and mandibular arches was analysed using dental panoramic radiographs and clinical records.
Transposition affected the maxillary dentition (76 per cent) more frequently than the mandibular dentition (24 per cent). Unilateral transposition accounted for 88 per cent of cases, with the maxilla being involved more commonly than the mandible. Overall, the most common transposition involved the maxillary canine and first premolar (58 per cent). Considering the jaws in isolation, the canine and first premolar were the most commonly affected teeth in the maxilla (83 per cent) whilst in the mandible, the canine and lateral incisor teeth were most commonly transposed (73 per cent). No significant difference in symmetrical distribution of the unilateral transposition sample occurred. There was evidence of associated hypodontia in 41 per cent of the sample; however, if third molars were excluded, this figure decreased to 25 per cent. Peg-shaped maxillary lateral incisors were judged to be present in 27 per cent of subjects, whilst 41 per cent had retained primary teeth; all of these, except one, were primary canines. Overall, the majority of the sample (76 per cent) demonstrated at least one of the dental anomalies under investigation.
Multivariate analysis showed associations between unilateral transposition, gender, and the presence of peg-shaped maxillary lateral incisors; whilst bilateral transposition was more closely associated with gender and the presence of retained primary teeth. There was a poor association between both unilateral and bilateral transposition and hypodontia. Together, these results suggest a mutifactorial aetiology to this disorder, with both genetic and environmental factors playing an important role.
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Introduction |
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TopSummaryIntroductionSubjects and methodsResultsDiscussionConclusionsReferences |
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Dental transposition is the positional interchange of two adjacent teeth, or the development or eruption of a tooth in a position normally occupied by a non-adjacent tooth (Peck et al., 1993
). In the general population the prevalence of this anomaly varies according to sample, but remains under 1 per cent in most investigations (Ruprecht et al., 1985; Sandham and Harvie, 1985; Burnett, 1999). Dental transposition can affect the maxillary (Peck and Peck, 1995; Chattopadhyay and Srinivas, 1996; Plunkett et al., 1998; Shapira and Kuftinec, 2001) or mandibular (Peck et al., 1998; Plunkett et al., 1998) dentition, either unilaterally or bilaterally (Figure 1); however, the canine tooth is almost always affected, with the majority of cases involving the canine/first premolar in the maxilla (Peck et al., 1993) and canine/lateral incisor in the mandible (Peck et al., 1998).
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Several theories have been proposed to account for dental transposition, including the interchange of developing tooth buds (Peck et al., 1993
, 1998), altered eruption paths (Gholston and Williams, 1984), the presence of retained primary teeth (Laptook and Silling, 1983) and trauma (Dayal et al., 1983). However, many types of transposition have been associated with factors that have a genetic basis, including female predilection (Peck et al., 1993, 1998; Plunkett et al., 1998; Shapira and Kuftinec, 2001), unilateral left-sided dominance (Peck et al., 1993; Shapira and Kuftinec, 2001), hypodontia (Peck et al., 1993, 1998; Plunkett et al., 1998; Shapira and Kuftinec, 2001), peg-shaped maxillary lateral incisor teeth (Peck et al., 1993, 1998; Plunkett et al., 1998; Shapira and Kuftinec, 2001), retained primary teeth (Shapira and Kuftinec, 2001) and Down syndrome (Shapira et al., 2000). On this basis it has been suggested that the fundamental aetiology for dental transposition is genetic, within a model of multifactorial inheritance (Peck et al., 1993, 1998).
To date, there have been few investigations of dental transposition with original samples of over 50 subjects (Peck et al., 1993, 1998; Peck and Peck, 1995; Plunkett et al., 1998; Shapira and Kuftinec, 2001). Although associations have been found between transposition and a variety of dental anomalies, most of these studies have employed relatively simple descriptive statistics (Peck et al., 1993, 1998; Plunkett et al., 1998; Shapira and Kuftinec, 2001). The aim of this study was to investigate the clinical features associated with dental transposition and to evaluate the aetiological basis of this condition using both descriptive and multivariate analysis.
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Subjects and methods |
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TopSummaryIntroductionSubjects and methodsResultsDiscussionConclusionsReferences |
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A total sample of 75 subjects, each demonstrating either maxillary or mandibular dental transposition, was collected from several hospital orthodontic departments and specialist orthodontic practices in London and the south east of England. The following were recorded for each subject:
- Classification of transposition
- Age at diagnosis
- Gender
- Presence of hypodontia
- Presence of peg-shaped maxillary lateral incisors
- Presence of retained primary teeth
).
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Statistical analysis
Multivariate analysis was applied to the sample using biplots (Gabriel, 1971). Data were analysed using Stata Statistical Software version 8.2 (StataCorp 2003, College Station, Texas, USA); where appropriate, significance was pre-determined at 
= 0.05.
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Results |
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TopSummaryIntroductionSubjects and methodsResultsDiscussionConclusionsReferences |
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Descriptive statistics
Each transposition was considered as a separate entity, which gave a total sample of 85, the distribution of which is shown in Figure 2. Unilateral transposition was by far the most common type, consisting of 66 cases (88 per cent). In contrast, bilateral transposition was only seen in nine cases (12 per cent). Transposition affected the maxillary (76 per cent) far more frequently than the mandibular (24 per cent) dentition. The most common transposition in the sample involved the maxillary canine and first premolar (58 per cent). Considering the jaws in isolation, the canine and first premolar were the most commonly affected teeth in the maxilla (83 per cent), whilst in the mandible, the canine and lateral incisor teeth were most commonly transposed (73 per cent). Overall, there was no significant difference in symmetrical distribution of the unilateral transposition sample. However, in the male sample the majority of unilateral transpositions were left-sided (63 per cent), whilst in females, the majority were right-sided (58 per cent).
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Evidence of associated hypodontia was analysed at three levels. Thirty-one subjects (41 per cent) demonstrated some form of hypodontia; however, if isolated third molar hypodontia was excluded from the sample, this figure reduced to 25 per cent. It has been suggested that 85 per cent of third molars are visible radiographically by 12 years of age (Clow, 1984
); application of this criterion resulted in 26 cases (35 per cent) being diagnosed with hypodontia. Peg-shaped maxillary lateral incisors were judged to be present in 20 cases (27 per cent). Retained primary teeth were present in 31 subjects (41 per cent) and 84 per cent of these were in the maxilla; all except one were primary canines. In the sample as a whole, 57 cases (76 per cent) exhibited at least one dental anomaly.
Biplot analysis
Biplots allowed a detailed visualization of the relationships between different classifications of dental transposition and certain associated dental features. Firstly, unilateral and bilateral transposition cases were analysed. For cases demonstrating unilateral transposition (Figure 3A) an association was found to exist between the gender of the subject and the presence of peg-shaped maxillary incisors; however, this was not strong. In addition, there was a poor association with the presence of hypodontia or retained primary teeth. In this sample, the presence of hypodontia was, however, closely associated with retention of the primary dentition. In contrast, bilateral transposition was more strongly associated with the presence of retained primary teeth and gender. The association with peg-shaped maxillary incisors and hypodontia was weak (Figure 3B).
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The unilateral transposition group was further analysed for maxillary and mandibular arches in isolation. In the maxilla, a similar pattern emerged; transposition was more closely associated with gender and the presence of peg-shaped maxillary incisors, whilst hypodontia and retained primary teeth were weakly associated (Figure 3C). In the mandible, the pattern was similar, although a closer association existed with peg-shaped maxillary incisors (Figure 3D).
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Discussion |
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TopSummaryIntroductionSubjects and methodsResultsDiscussionConclusionsReferences |
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This investigation focused upon 85 cases of dental transposition in 75 subjects. Within this group, maxillary transposition accounted for the majority of cases, which is broadly in agreement with previous studies (Peck et al., 1993
; Plunkett et al., 1998; Shapira and Kuftinec, 2001) and most commonly involved the canine and first premolar (Peck et al., 1993; Peck and Peck, 1995; Plunkett et al., 1998; Shapira and Kuftinec, 2001). None involved the central incisors or molar teeth, consistent with these forms of transposition being extremely rare (Peck and Peck, 1995). In contrast to the maxilla, mandibular transposition was found to be a less common phenomenon, involving canine and lateral incisor teeth more frequently (Peck et al., 1998; Plunkett et al., 1998). Bilateral transposition was found to be less common than unilateral transposition in both arches (Peck et al., 1993, 1998; Peck and Peck, 1995; Plunkett et al., 1998; Shapira and Kuftinec 2001). In all of the bilateral cases, the same teeth were affected on each side; asymmetrical bilateral transposition is extremely rare (Al-Shawaf, 1988).
The majority of subjects demonstrated at least one of the dental anomalies under consideration. Hypodontia, both including and excluding third molars, peg-shaped maxillary lateral incisors and retained primary teeth were all observed with a prevalence greater than the population norm (Meskin and Gorlin, 1963; Muller et al., 1970; Bot and Salmon, 1977; Mattheeuws et al., 2004). This frequent association between dental anomalies within affected individuals provides a strong argument for a genetic basis to these conditions (Baccetti, 1998). Such findings, in association with dental transposition, have been used as a persuasive argument for a significant genetic basis for this condition in both arches (Peck et al., 1993, 1998). However, studies that have focused upon canine transposition have also found evidence for local rather than genetic factors being the predominant aetiological component (Plunkett et al., 1998; Shapira and Kuftinec, 2001).
The present study has highlighted the complex relationships that exist in the aetiology of dental transposition. The descriptive statistical analysis suggests a clear association between inherited dental anomalies and transposition; however, this is less clear when multivariate analysis was applied to the sample. Research into dental anomalies and the variable features associated with these conditions generates multivariate data sets where the value of simple tests for pairs of independent variables is limited. This type of analysis can lead to serious and incorrect errors of interpretation due to Simpson's paradox (Simpson, 1951; Everitt, 1995; Agresti and Coull, 1996). The association between two independent variables may be identical within the levels of a single third variable, but can take on a different value when the association measure is calculated from pooled data. To avoid this, the data were analysed using biplots (Gabriel, 1971). Biplots are the multivariate equivalent of the bivariate scatter plot. They are an approximation to the underlying multivariate distribution, typically in two dimensions, and representations of underlying variables are superimposed on the plot. Biplots are useful for the visual inspection of a multivariate data matrix, allowing the identification of patterns, regularities and outliers. Thus they are capable of graphically displaying large multivariate data sets with complex associations and interactions, and are closely related to principal component analysis in that the first dimension explains the highest attributable variance in the data set, the second dimension the second highest, and so on (Gabriel and Odoroff, 1990). The principle observations are plotted as points and the associated variables as vectors from the origin. Points lying close together have similar values and patterns, whilst the vectors represent correlations between variables; the smaller the angle the higher the correlation, and vectorial direction provides the sign of correlation. These plots therefore provide a useful visual description of the relationships within multivariate data sets (Gower and Hand, 1996).
Biplots demonstrated only a weak association between unilateral transposition and one dental anomaly under genetic influence, peg-shaped maxillary lateral incisors; this relationship being even weaker for bilateral transposition. Overall, the most surprising finding was the poor association between transposition and hypodontia, even though the sample exhibited hypodontia at higher levels than might be expected in a normal population (Mader and Konzelman, 1979; Mattheeuws et al., 2004).
Therefore, a fundamental question with regard to the aetiology of dental transposition is whether this condition has a purely genetic basis or if environmental factors play a role. The most likely explanation, certainly based upon the findings of this study, is that the condition represents a multifactorial disorder, with both genetic and environmental contributions being important. The purest argument for a genetic cause is that transposition arises during development, from a disturbance in the order of developing tooth follicles. In broad support of this is the knowledge that genes play an important role in patterning the dentition (Jernvall and Thesleff, 2000; Cobourne and Sharpe, 2003; Tucker and Sharpe, 2004). Combinatorial expression of homeobox-containing transcription factors pattern the presumptive dental axis prior to dental initiation, and manipulation of these domains can result in the transformation of tooth type (Sharpe, 1995; Tucker et al., 1998). However, no mutations have been identified in any subjects demonstrating transposition. Indeed, mutations in several homeobox genes cause selective tooth agenesis rather than transposition, almost certainly because of the important reiterative role these genes play during the later stages of odontogenesis (Vastardis et al., 1996; Stockton et al., 2000; van den Boogaard et al., 2000; Lammi et al., 2003). Within such a purely genetic model, the canine tooth might be more commonly transposed because it lies at the boundary between the developing incisor and premolar fields of development, a region that is possibly more susceptible to particular thresholds of gene activity for normal patterning to occur (Thesleff, 1996). Indeed, Peck et al. (2002) used canine malposition as a model to suggest a molecular basis for this condition. The authors postulated that HOX genes may play a role, although this cannot be true because HOX genes are not expressed in the maxillary and mandibular primordia (Hunt and Krumlauf, 1991). It is not inconceivable, however, that other homeobox-containing transcription factors that are expressed in these regions may also be implicated in the aetiology of ectopic positioning of the canine.
However, the canine tooth has a long path of eruption, is theoretically more susceptible to deflection during its long eruptive descent, and is frequently associated with transposition. Opinions differ as to the relative contribution of genetics and environment in this eruptive process (Peck et al., 1994, 1995; Becker, 1995), but there is currently too little robust statistical or genetic evidence to definitively ascribe malposition of the permanent canine as an isolated disorder of either genetics or environment. Certainly in non-syndromic forms of cleft lip and palate, both genetic mutations and environmental factors seem to play a role in defining thresholds of susceptibility within affected individuals (Cobourne, 2004).
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Conclusions |
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TopSummaryIntroductionSubjects and methodsResultsDiscussionConclusionsReferences |
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The results of this investigation suggest that dental transposition represents a multifactorial condition. Both genetic and environmental factors seem to be involved in the aetiology of transposition and the relationships are complex. Large-scale population-based studies will be required to further refine our understanding of the genetics of this anomaly.
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Acknowledgement |
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We are grateful to the following clinicians who were kind enough to provide cases for this study: Siamack Bagheri, Dirk Bister, Charlotte Conroy, Geraldine Dooley, Richard George, Sarah Good, David Horobin, Nicola Johnson, Gary Mancini, Lee Ng, Jackie Silvester, Pam Thakral, Sarah Turner and David Young.
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References |
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