Rosalia Leonardi, Mauro Farella, Martyn T. Cobourne
Tooth transposition has been defined as a form of ectopic eruption, involving the positional interchange of two adjacent teeth or the development and eruption of a tooth into a position normally occupied by a non-adjacent tooth (Peck et al., 1993). The aetiological basis of this anomaly is still not completely understood; however, there is good evidence to suggest a genetic basis (Chattopadhyay and Srinivas, 1996; Shapira and Kuftinec, 2001; Ely et al., 2006). Dental transposition is often seen in association with other congenital dental anomalies, such as hypodontia and peg-shaped or diminutive lateral maxillary incisors (Peck et al., 1993, 1998; Plunkett et al., 1998; Ely et al., 2006); there is a marked female predilection (Peck et al., 1998; Plunkett et al., 1998; Ely et al., 2006) and unilateral left-sided dominance (Peck et al., 1993; Plunkett et al., 1998). However, environmental factors can also contribute to the occurrence of transposition, including retained primary teeth (Laptook and Silling, 1983) and previous dental trauma (Dayal et al., 1983). Therefore, a multifactorial model has been suggested, with a genetic predisposition existing under the varying influence of local environmental factors (Peck et al., 1993; Plunkett et al., 1998; Ely et al., 2006). More recently, a number of localized dental anomalies, such as hypodontia and palatal displacement of the maxillary canine, have been associated with calcification of the interclinoid ligament (ICL) or sella turcica bridging (Leonardi et al., 2006). The presence of intracranial clinical calcifications in addition to those affecting the dentition is highly suggestive of a genetic aetiology underlying both tooth anomalies and those in a broader area of the orofacial field (Pirinen et al., 1996). Indeed, several studies conducted on the shape of the sella turcica have described significant shape variation associated with this structure (Tetradis and Kantor, 1999); moreover, they have concluded that the morphological appearance is established early in embryonic development (Kjær et al., 1998; Nielsen et al., 2005).
Calcification of the ICL, or sella turcica bridging, has been shown to occur in up to 1.1–13 per cent of the general population (Bergland et al., 1968; Cederberg et al., 2003; Axelsson et al., 2004a; Alkofide, 2007) with an increased prevalence in those with severe craniofacial disproportion (Becktor et al., 2000; Jones et al., 2005). However, a clear distinction between a true bony union of the anterior and posterior process (sella turcica bridge) and ‘overlapping’ on lateral radiographs is difficult to determine (Axelsson et al., 2004a). In addition, sella turcica bridging is also seen in association with inherited developmental conditions that can affect the craniofacial region, such as nevoid basal cell carcinoma syndrome (NBCCS) and Williams syndrome (Kimonis et al., 1997; Axelsson et al., 2004b). Given the evidence for a genetic basis underlying both dental transposition and sella turcica bridging and the common embryonic origins associated with these tissues, the aim of this study was to determine any possible association between these two conditions. The null hypothesis was that no association between the two conditions would exist and might only be expected by chance.
SUBJECTS AND METHODS
The clinical records of subjects affected by dental transposition were collected from various hospital orthodontic departments and specialist practices in London, the south-east of England, and Catania, Italy. A diagnosis of tooth transposition was made on the basis of clinical examination and confirmed radiographically. This study sample consisted of 21 Caucasians (7 males and 14 females; mean age 14.5 years; SD 2.2 years) having either maxillary or mandibular dental transposition. Dental panoramic tomograms (DPTs) were used to confirm the presence of a true transposition, involving both the crown and root of the affected teeth. Malocclusion type was not a criterion for sample selection. However, exclusion criteria included subjects with severe craniofacial deviations, who required combined surgical–orthodontic treatment (Becktor et al., 2000), the presence of a cleft lip and palate, craniofacial syndromes, a history of facial trauma, or multi-reagent chemotherapy.
The control group comprised 70 Caucasian subjects (31 males and 39 females; mean age 13.8 years; SD 1.8 years) without dental anomalies, who were randomly selected from those referred for orthodontic treatment within the same departments during the previous 3 years. Forty-one per cent of the subjects had a skeletal Class I relationship, 55 per cent a Class II, and 4 per cent a Class III. Classification of skeletal type was based on ANB angle (Alkofide, 2007). The exclusion criteria were the same as for the study population.
Cephalometric tracing of sella turcica
All cases and controls were documented with lateral skull cephalometric radiographs and dental panoramic tomograms. Only radiographs that had the clearest reproduction of the sella turcica area were selected. In order to quantify the extent of a sella turcica bridge from each profile radiograph. The contour of the pituitary fossa from the tip of the dorsum sellae to the tuberculum sella, was traced on Ultraphan transparent acetate sheets in a darkened room on a laminator using a Pentel 0.5 mm lead pencil and measured manually by one observer (RL). The sella turcica length (distance from tuberculum sella to the tip of the dorsum sella) and antero-posterior greatest diameter (distance from tuberculum sella to the furthest point on the inner wall of the pituitary fossa) were measured (Figure 1). It should be emphasised that the length measurement is representative of ICL calcification, and as such, is not a real bone measurement but a measurement between calcified areas.
All measurements were made to the nearest 0.1 mm using a calliper. Sella turcica length and diameter were compared using a standardized scoring scale (Leonardi et al., 2006). Briefly, if the length was greater than or equal to three-quarters of the greatest antero-posterior diameter, sella was scored as type I (no calcification); type II if the length was less than or equal to three-quarters (ICL partially calcified); and type III for a radiographically visible diaphragma sella (ICL completely calcified; Figure 2). The greatest postero-anterior sella turcica diameter measurement was divided by four and the value obtained was compared with sella turcica length.
Fig.1 – Normal sella turcica morphology and reference lines used for determining bridging. TS, tuberculum sella; DS, dorsum sella. The black line represents sella turcica length, while the dashed line represents the greatest antero-posterior diameter.
Reliability of measurements
Duplicate tracings of 10 radiographs were made on two separate occasions by the same author (RL) with a 2 week interval between tracings and the random error was assessed (Houston, 1983). The mean difference between the first and second measurements was not significant. Sella measurement errors for length and diameter were considered minor as they ranged from 0.15 to 0.25 mm.
Data were analysed by means of conventional descriptive statistics. Chi-square and Fisher’s exact tests were used for subsequent analyses. Bonferroni correction was used for post hoc multiple comparisons. The strength of association between sella turcica bridging and dental transposition was estimated using the odds ratio (±95 per cent confidence interval). Statistical analyses were carried out by means of the Statistical Package for Social Science (Release 15.0; SPSS Inc., Chicago, Illinois, USA) with a probability level of 0.05 considered statistically significant.
All subjects in the study sample were diagnosed with unilateral transposition, predominantly affecting the maxilla with the exception of one subject demonstrating maxillary bilateral transposition. In 12 of the 21 subjects, maxillary canine first premolar transposition was found, whereas in 6 of 21, transposition involved the maxillary canine and lateral incisor. In the remaining three subjects, a transposition between the mandibular canine and lateral incisor was present.
The overall proportions of types I, II, and III sella calcification (Figures 2 and 3) differed significantly between the subjects and the controls (chi-square = 7.4; df = 2; P = 0.025; Fisher’s exact test; P = 0.042). Post hoc comparisons indicated that a type III sella was more frequent in cases than in controls (P < 0.05) Figure 4.
Fig.2 – Type I [no calcification of interclinoid ligament (ICL)], type II (ICL partially calcified), and type III (ICL completely calcified).
The absolute and relative frequencies of anomalies associated with sella turcica in the samples are shown in Figure 4. In subsequent analyses, subjects with a partial or complete calcification of the ICL were grouped in a single category including all sella turcica anomalies (i.e. type II + type III). The proportion of these anomalies was still significantly higher in the dental transposition cases than in the controls (57.1 per cent versus 31.4 per cent; chi-square = 4.6; df = 1; P = 0.033), with an odds ratio (95 per cent confidence interval) of 2.9 (1.1–7.9).
Fig.3 – Lateral cephalometric radiographs of patients with (A) dental transposition and bridging of the sella turcica (B) dental transposition and partial bridging of the sella turcica and (C) dental transposition and no calcification of sella, although a cervical fusion between C2 and C3 can be observed (C).
Fig.4 – Absolute frequencies of sella anomalies in patients and controls. Type I [no calcification of interclinoid ligament (ICL)], type II (ICL partially calcified) and type III (ICL completely calcified).
This study describes a previously unreported but clear association between sella turcica bridging and dental transposition. The pituitary gland originates in the embryo as a result of interaction between two ectodermal tissues; neural ectoderm gives rise to the posterior pituitary, whereas a portion of the oral ectoderm develops into the anterior pituitary gland (Treier and Rosenfeld, 1996; Burrows et al., 1999; Sheng and Westphal, 1999). The pituitary fossa itself is situated within the body of the sphenoid bone and differentiates directly from the hypophyseal cartilage of the early chondrocranium. The hypophyseal cartilage is derived from cranial neural crest cells; however, the body of the sphenoid has been shown to include a mesodermal contribution in its more posterior region, at least in the mouse (McBratney-Owen et al., 2008). Teeth develop within the frontonasal process and the maxillary and mandibular processes of the first branchial arch as a result of molecular interaction between the oral epithelium and underlying neural crest cells that migrate into these regions. The establishment of patterning along the dental axis is thought to take place very early in the developmental process, with fixed domains of homeobox gene expression being established within neural crest cells as a result of signalling from the epithelium (Sharpe, 1995, 2001). A number of common molecular pathways are involved during the early stages of pituitary (Ericson et al., 1998; Sheng and Westphal, 1999; Dassule et al., 2000; Treier et al., 2001), dental (Neubuser et al., 1997; Dassule et al., 2000; Gritli-Linde et al., 2002), and skull (Kim et al., 1998) development, which include signalling mediated through bone morphogenetic proteins, fibroblast growth factors, and hedgehog proteins. Moreover, disruption in these signalling pathways can give rise to inherited syndromic conditions that can include calcification of the sella turcica as part of the clinical spectrum of the disease. A good example of this is provided by NBCCS or Gorlin-Goltz syndrome, an autosomal dominant hamartomatous disorder characterized by multiple basal cell carcinomas affecting the skin, medulloblastoma, multiple and recurrent odontogenic keratocysts of the jaws, spine and rib anomalies, and craniofacial defects, which include calcification of the dura mater and sella (Evans et al., 1993; Shanley et al., 1994; Gorlin, 1995; Kimonis et al., 1997). The gene mutated in NBCCS has been identified as PATCHED-1 (Wicking et al., 1997; Lindström et al., 2006), which is the principal receptor for the sonic hedgehog ligand (Goodrich et al., 1996; Johnson et al., 1996).
The present investigation analysed the frequency of sella turcica bridging in a sample of subjects affected by dental transposition. The rationale came from previous observations demonstrating an increased prevalence of localized dental anomalies and extremes of craniofacial skeletal variation in subjects with this condition (Becktor et al., 2000; Leonardi et al., 2006). Furthermore, it has been demonstrated that anomalies associated with sella turcica can be a feature of human craniofacial syndromes (Kimonis et al., 1997). The increased frequency of complete and partial calcification of sella, in subjects with dental transposition, provides further evidence of a genetic basis for these conditions and some commonality in the molecular pathways involved. Indeed, as calcification in this region can appear during early childhood, it may provide an aid to the early diagnosis of some conditions or act as a diagnostic predictor of susceptibility for localized dental problems. Certainly, the findings of this study indicate that subjects with calcification in the region of sella are at potential risk of developing dental transposition. However, care should be taken in making a diagnosis of sella turcica bridging as the appearance of fusion between the anterior and posterior clinoid processes can be due to radiographic superimposition of these structures and not necessarily real bony fusion (Becktor et al., 2000; Axelsson et al., 2004a). In the present study, if this had occurred, it might have been expected to affect both subject samples, which was not the case. Moreover, even though the majority of sella turcica bridges are detectable early in life, in some cases, calcification develops over time and might only be observed on lateral cephalometric radiographs taken at a later stage.
While this association may potentially improve early diagnosis of orthodontic problems, particularly in alerting the clinician to possible ectopic tooth development, some caution must be exercised. The only way of diagnosing early calcification of the sella turcica is with a lateral skull radiograph and current guidelines would suggest that in children under 10 years of age, this form of radiograph is only justified in the presence of a severe skeletal discrepancy, which may require early treatment or monitoring (Isaacson et al., 2008). However, the results of this investigation would suggest that in some cases, particularly where there may be a family history of tooth impaction or early occlusal indications of potential ectopic eruption, some consideration might be given towards radiographic examination of sella as a further predictor. This may allow the instigation of suitable measures to prevent subsequent tooth impaction or transposition (Ericson et al., 1998; Shapira and Kuftinec, 2001).
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