Establishing the diagnostic criteria for eruption disorders based on genetic and clinical data.

INTRODUCTION: Proper diagnosis and management of eruption disturbances remains challenging but is critical to a functional occlusion. The objective of this study was to establish definitive criteria to differentiate and diagnose eruption disorders, specifically primary failure of eruption (PFE) and ankylosis. METHODS: Sixty-four affected persons were placed into 3 cohorts: PFE diagnosed through confirmed PTH1R mutation (n = 11), PFE diagnosed based on clinical criteria (n = 47), and ankylosis diagnosed based on clinical criteria (n = 6). These groups were assessed to identify clinical features that differentiate PFE and ankylosis. RESULTS: Ninety-three percent of the subjects in the genetic and clinical PFE cohorts combined (n = 58) and 100% in the genetic PFE cohort had at least 1 infraoccluded first permanent molar. Additionally, a novel functional PTH1R mutation, 1092delG, was identified and linked to PFE in the deciduous dentition. CONCLUSIONS: An infraoccluded, supracrestal first molar is a hallmark of PFE, often involving both arches in the permanent or deciduous dentition, and with unilateral or bilateral affection, infraoccluded second premolar or second molar, and multiple affected adjacent teeth. Our results further suggest that PFE and ankylosis might be clinically indistinguishable without knowledge of prior trauma, treatment history, genetic information, or obliteration of the periodontal ligament space.

Triplets with bilateral palatally displaced canines in association with third molar agenesis: an example of biologically related dental anomaly patterns?

This case series shows male triplets with similarly positioned palatally displaced canines and agenesis of third molars. It supports findings reported previously in the literature suggesting a genetic origin for the palatally displaced canine and other dental anomalies which may be biologically related.

[Tooth and bone research using genetically modified mice].

Teeth and bone are both hard tissues and composed of hydroxyapatite. Tooth development initiates with the invasination of oral epithelium, followed by aggregation of supporting ectomesenchymal cells. From mouse study, numbers of molecules have been discovered to relate tooth development. These discoveries have helped to clarify the responsible genes of human genetic disorders with abnormal tooth number and structure. During tooth development, teeth erupt into the outer environment, oral cavity. From this point, teeth are completely different from bone which is always covered by soft tissues. Tooth eruption is composed of two different processes, that is, eruption pathway formation and vertical tooth movement. In this review, mutant mice with abnormal tooth development and eruption are introduced, and molecular mechanism required for this process is discussed.

Agenesis of maxillary lateral incisors and associated dental anomalies.

INTRODUCTION: The objectives of this study were to evaluate the prevalence of dental anomalies in patients with agenesis of maxillary lateral incisors and to compare the findings with the prevalence of these anomalies in the general population. METHODS: A sample of 126 patients, aged 7 to 35 years, with agenesis of at least 1 maxillary lateral incisor was selected. Panoramic and periapical radiographs and dental casts were used to analyze other associated dental anomalies, including agenesis of other permanent teeth, ectopia of unerupted permanent teeth, microdontia of maxillary lateral incisors, and supernumerary teeth. The occurrence of these anomalies was compared with prevalence data previously reported for the general population. Statistical testing was performed with the chi-square test (P <0.05) and the odds ratio. RESULTS: Patients with maxillary lateral incisor agenesis had a significantly increased prevalence rate of permanent tooth agenesis (18.2%), excluding the third molars. The occurrence of third-molar agenesis in a subgroup aged 14 years or older (n = 76) was 35.5%. The frequencies of maxillary second premolar agenesis (10.3%), mandibular second premolar agenesis (7.9%), microdontia of maxillary lateral incisors (38.8%), and distoangulation of mandibular second premolars (3.9%) were significantly increased in our sample compared with the general population. In a subgroup of patients aged 10 years or older (n = 115), the prevalence of palatally displaced canines was elevated (5.2%). The prevalences of mesioangulation of mandibular second molars and supernumerary teeth were not higher in the sample. CONCLUSIONS: Permanent tooth agenesis, maxillary lateral incisor microdontia, palatally displaced canines, and distoangulation of mandibular second premolars are frequently associated with maxillary lateral incisor agenesis, providing additional evidence of a genetic interrelationship in the causes of these dental anomalies.

The role of Cone beam CT in the evaluation and management of a family with Gardner's syndrome.

Gardner's syndrome (GS) is a hereditary autosomal dominant disease of the colon that presents with extra-colonic manifestations such as osteomas, skin lesions and dental abnormalities. Osteomas are commonly found in the skull, jaws and the paranasal sinuses. We present a family of four sisters affected with GS with a wide range of anomalies. The role of Cone beam computed tomography (CBCT) in the early detection and evaluation of osteomas and dental anomalies with precise assessment of their relationship to adjacent anatomic structures is described here in detail. The careful interpretation of CBCT may be of a great value in surgical and orthodontic treatment planning in the presence of jaw lesions. Management of dental problems in GS may be challenging due to the presence of odontomas and increased bone density. A multidisciplinary approach in the management of GS can achieve the best treatment results.

Malposition of unerupted mandibular second premolar in children with palatally displaced canines.

OBJECTIVE: To test the hypotheses that (1) the distal angulation of unerupted mandibular premolar (MnP2) is significantly greater in children with palatally displaced canines (PDC) than in those in a control sample; and (2) delayed tooth formation is significantly more frequent in children with both malposed MnP2 and PDC than in children with PDC only. MATERIALS AND METHODS: We examined retrospectively panoramic radiographs from 43 patients with PDC who had no previous orthodontics. A control sample consisted of age- and sex-matched patients. The distal angle formed between the long axis of MnP2 and the tangent to the inferior border was measured. Dental age was evaluated using the Koch classification. RESULTS: A significant difference was observed between the mean inclination of the right side MnP2 in the PDC group (75.4 degrees) and that of the control group (85.8 degrees). This difference was highly statistically significant (P < .0001). The same evaluation was carried out for the left side, with similar results. The average dental age was found to be delayed in patients who showed both abnormalities (malposed MnP2 and PDC) compared with patients who showed the PDC anomaly only. CONCLUSION: Both hypotheses are retained. Statistically, PDC and MnP2 malposition are significantly associated suggesting a common genetic etiology, despite taking place on opposite jaws. While the presence of PDC or MnP2 anomaly has been associated with a delay in tooth formation, we find the presence of both anomalies to show a more profound delay. Our findings suggest a delay in tooth formation as a possible common genetic mechanism for these 2 malposition anomalies.

Ectopic maxillary canines: segregation analysis and a twin study.

The etiology of ectopic canines is controversial, with opinion divided as to a genetic or environmental mechanism. This study addressed the hypothesis that genetic factors play a role in the etiology of ectopic maxillary canines. Sixty-three probands were identified, and information on the dental status of 395 relatives was determined. Pedigrees were constructed and the Relative Risk calculated. Complex segregation analysis was carried out by means of the Pedigree Analysis Package. The best mathematical model obtained was a single dominant gene with autosomal transmission, incomplete penetrance, and highly variable expression. Only two of seven pairs of monozygotic twins were concordant for ectopic canines. This is consistent with environmental or epigenetic variables affecting the phenotype. The low concordance rate is consistent with the low penetrance determined by the segregation analysis and further supports the existence of environmental factors.

Downregulation of matrix metalloproteinases in hyperplastic dental follicles results in abnormal tooth eruption.

In this study, we compared the gene expression profiles of non-syndromic hyperplastic dental follicle (HDF) fibroblasts and normal dental follicle (NDF) fibroblasts using cDNA microarrays, quantitative PCR, and immunohistochemical staining. Microarray analysis showed that several collagens genes were upregulated in the HDFos, including collagen types I, IV, VIII, and XI and TIMP-1, -3, and -4 (fold ratio > 2.0). In contrast, the expression of MMP-1, -3, -10, and -16 together with IL-8 was more than two fold downregulated. The differential expression of the genes encoding alkaline phosphatase, MMP-1, -3, -8, and IL-8 was confirmed by quantitative RT-PCR, while that of 24 HDFs and 18 NDFs was confirmed by immunohistochemical analysis. However, HDFs showed stronger expression of MMP-3 than NDFs (P < 0.001). Collectively, these results indicate that defective regulation of MMPs mediating connective tissue remodeling may be responsible for abnormal tooth eruption.

Dental transposition as a disorder of genetic origin.

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.

Maxillary canine anomalies and tooth agenesis.

The aims of the study were to analyse the records of 26 subjects (18 females, eight males) with maxillary canine-first premolar transposition (Mx.C.P1) together with 160 subjects with a palatally displaced canine (PDC) to determine the pattern of tooth agenesis in these cases and to compare them with similar samples reported in the literature. A strong association between Mx.C.P1, lateral incisor and lower second premolar agenesis was found, with a 20 per cent prevalence of lateral incisor agenesis and a 24 per cent prevalence of lower second premolar agenesis. There was a lesser association with third molar (M.3) agenesis, with a prevalence of 52.2 per cent. Weaker associations were found for a PDC, with a prevalence of 5 per cent for lateral incisor agenesis. The prevalence of lower second premolar (5 per cent) and M.3 (27.5 per cent) agenesis approached reference values. Evidence for the implication of the MSX1 or PAX9 genes in the aetiology of PDC was weak.

[Tooth transposition: results of an enquiry among practitioners]. / Les transpositions intra-maxillaires: résultats d'une enquête auprès des praticiens.

A questionnaire was sent to orthodontists in order to analyse transpositions of teeth and their treatment. The results of this study confirm that most transpositions are maxillary canine/premolar transpositions. These transpositions were found to be often associated with other dental abnormalities (such as agenesis and peg-shaped laterals). Considerable evidences supports they are genetic in origin, but, in accordance with the demands of evidence-based science, further study is needed to prove it. The results suggest that most practitioners try to correct transposition despite the many difficulties involved. Early diagnosis did not reduced treatment time nor diminish difficulties.

Dentoskeletal features associated with unilateral or bilateral palatal displacement of maxillary canines.

The aim of the present study was to analyze the prevalence and distribution of palatally displaced maxillary canines (PDC) in a large orthodontic population, and to investigate the associations between PDC, craniofacial features, and other dental anomalies such as aplasia or small-sized upper lateral incisors. An initial sample of 5000 subjects was evaluated. The reference values were calculated in a control group of 1000 subjects that was extracted from the initial sample. Chi-squared tests were used for statistical comparisons. The prevalence rate of PDC was 2.4%, with a male-to-female ratio of 1:3. PDC subjects with low angle vertical relationships showed a significantly high prevalence rate (60.2%). Unilateral PDC was significantly associated with aplasia of upper lateral incisors, whereas bilateral PDC was associated with aplasia of third molars. PDC showed reciprocal significant associations with bilateral small-sized upper lateral incisors. None of the three hypotheses offered in support of the "guidance theory" in the etiology of PDC were corroborated by the findings of the present study. The occurrence of other dental anomalies concurrent with PDC, sex differences, and the bilateral expression of PDC, all confirm the genetic component in the etiology of this tooth disturbance.

Palatally displaced canine anomaly in monozygotic twins.

The palatally displaced canine (PDC) anomaly is a tooth malposition occurring in 1% to 3% of most populations. From the results of family studies, the PDC phenotype appears to be under strong genetic influence. In this study we report monozygotic (MZ) twin girls with bilateral PDC expression. The finding of PDC anomaly in MZ twins--to our knowledge, the first such published case--lends further support to evidence of genetic control of the PDC anomaly.

Maxillary canine displacement and genetically determined predisposition to disturbed development of the dentition.

BACKGROUND: The relationship between maxillary canine displacement and the simultaneous occurrence of "genetically determined predisposition to disturbed development of the dentition" as defined by Hoffmeister was investigated in 675 patients. PATIENTS AND METHODS: Panoramic radiographs taken of each patient during the first and the second mixed dentition periods were evaluated. Canine inclination and the distance between the tip of the canine and a line connecting the cusps of the molars were computed in five different age groups according to Dausch-Neumann. RESULTS: Statistical analysis revealed 34 patients with "potential canine displacement", who exhibited further symptoms of "genetically determined predisposition to disturbed development of the dentition" significantly more frequently than the total group. The symptoms concerned were agenesia, displaced tooth buds, rotated or tilted incisors, aplasia and microdontia of lateral incisors. CONCLUSION: Careful follow-ups in patients with a predisposition to disturbed dental development enables risks to be anticipated and canine displacement to be detected at an early stage.

Concomitant occurrence of canine malposition and tooth agenesis: evidence of orofacial genetic fields.

Certain discrete malpositions of the human canine tooth and agenesis of at least 1 tooth (hypodontia) are abnormalities known to occur together frequently. This study examines the specificity of tooth-agenesis sites associated with the occurrence of 3 unambiguous canine malpositions: palatally displaced canine (PDC; n = 58), mandibular lateral incisor-canine transposition (Mn.I2.C; n = 60), and maxillary canine-first premolar transposition (Mx.C.P1; n = 43). A fourth sample was formed from 4 cases of combined occurrence of PDC and Mn.I2.C, the only combination-phenotype noted among the 161 subjects. Oral panoramic radiographs were used to identify agenesis of at least 1 third molar (M3), mandibular second premolar (MnP2), and maxillary lateral incisor (MxI2)-the 3 most frequently absent tooth types among people of European descent. PDC and Mn.I2.C transposition appear to be associated with significantly increased M3 agenesis (P <.01), representing the posterior orofacial field, and Mx.C.P1 transposition appears to be associated with conspicuously elevated MxI2 agenesis (P <.001), representing the anterior orofacial field. MnP2 agenesis appears to represent an intermediate field, found in significantly elevated frequencies with all 3 canine positional anomalies. Coupling these new clinical findings with results from recent molecular studies, we suggest that transcription factors such as MSX1 and PAX9, which have been associated with agenesis of molars, might be involved in the genetic control of Mn.I2.C transposition and PDC, tooth malpositions connected here with the specific expression of posterior-field (M3) hypodontia.

Maxillary canine transpositions in two brothers and one sister: associated dental anomalies and genetic basis.

Transposition is an uncommon dental anomaly involving positional interchange of two teeth. The maxillary canine is the tooth more frequently transposed in man. Maxillary canine-first premolar appears to be the most common type of tooth transposition, followed by maxillary canine-lateral incisor transposition. Maxillary canine transpositions are frequently associated with other dental abnormalities such as agenesis and pegshaped incisors. This report describes the presence of transposed canines in one sister and two brothers. The female showed bilateral maxillary canine-first premolar transposition with the left canine fully mesial to its neighboring first premolar, and the right canine blocked-out facially between the first and second premolar. One of the brothers showed full maxillary left canine-lateral incisor transposition. The other brother showed maxillary canine-first premolar transposition and agenesis of maxillary lateral incisors, with the left canine blocked-out facially between the first and second premolar. Findings from this case report and other previously published cases provide strong evidence that maxillary canine transpositions are a disturbance of tooth order and eruptive position resulting from genetic influences within a multifactorial inheritance model.

Congenital tooth anomalies and malocclusions: a genetic link?

The aim of the present study was to investigate putative relationships between different malocclusions such as Class III and Class II division 1, and congenital tooth anomalies. Two-hundred Class III and 215 Class II division 1 patients were examined for the presence of any of the following congenital tooth anomalies: maxillary incisor hypodontia, maxillary canine impaction, transpositions, supernumerary teeth, and tooth agenesis. Their occurrence rates were then calculated as a percentage of the total sample and were compared for statistical differences. The results revealed no statistical difference (P > 0.05) in the occurrence rates of upper lateral incisor agenesis, peg-shaped laterals, impacted canines, or supernumerary teeth between the Class III and the Class II division 1 malocclusions. When the occurrence rate of all congenital tooth anomalies was compared between the two malocclusions, Class III subjects showed significantly higher rates (P < 0.05). Comparison with published surveys on general populations showed similar occurrence rates. It can be concluded that subjects with Class III and Class II division 1 malocclusions show patterns of congenital tooth anomalies similar to those observed in the general population. Congenital tooth anomalies may represent another criterion for the study of malocclusion, with respect to their origin and development.

The etiology of palatal displacement of maxillary canines.

OBJECTIVES: To test the hypothesis that palatal displacement of the maxillary canine is completely under genetic influence. DESIGN: A randomized controlled design studied cases affected by a severe expression of lateral incisor anomaly on one side and by milder expression of the same anomaly on the other. Comparison of frequency of occurrence of unilateral palatally displaced canine measured in each. Each side acted as control for the other within the same individual. SETTING AND SAMPLE POPULATION: The Departments of Orthodontics of the Universities of Jerusalem and Tel Aviv and in private practice. From approximately 12,000 consecutively treated patients, all those exhibiting an anterior maxilla with a missing lateral incisor on one side, a peg-shaped or reduced lateral incisor on the other, and a palatally displaced canine (n = 19). OUTCOME MEASURE: Missing lateral incisors, peg-shaped, and reduced lateral incisors (all genetically determined characters) have been shown to be associated with palatal displacement of the canine. The canine displacement is presumed by some authorities to be similarly genetically determined. If this is so, then the impacted canine should occur with equal frequency on either side in the patient with a missing lateral incisor on one side and a peg-shaped or reduced lateral incisor on the other. RESULTS: The canine aberration occurred far more frequently on the side of the diminutive lateral incisor. CONCLUSION: There is an environmental factor involved in the palatal displacement of maxillary canines.