A New Surgical Assistance Aid for Mesiodens Extraction Based on the Ideal Approach.

BACKGROUND: To date, the classification of mesiodens has been based on the location, crown orientation, and morphology; however, there is no assistance aid focusing on choosing surgical approach. PURPOSE: This study aimed to introduce and evaluate a new surgical assistance aid for mesiodens extraction based on surgical approach. STUDY DESIGN, SETTING, SAMPLE: For the retrospective trial part of this study, case data from mesiodens patients who had surgery at the Affiliated Stomatological Hospital was collected, and a new surgical assistance aid was developed. A prospective randomized controlled trial was conducted on mesiodens patients who were seen in our department (patients with one mesiodens were included). PREDICTOR VARIABLE: The predictor variable was surgical approach either with or without the surgical assistance aid. Subjects were randomized to one of the two study groups. For subjects assigned to the group using the surgical assistance guide, the approach was selected according to the aid detailed in this study. For subjects assigned to the group without the surgical assistant aid, 2 residents chose an approach based on their judgment and review of relevant imaging and physical examination. MAIN OUTCOME VARIABLES: The preoperative evaluation time, operative time, and complications associated with surgery were recorded separately for the two groups. COVARIATES: The age and sex were also recorded. ANALYSES: Variables were analyzed using the independent t-test and χ2 test. The level of statistical significance is P < .05. RESULTS: In the retrospective trial part, a new surgical assistance aid for mesiodens extraction was developed based on the ideal surgical approach. In the prospective randomized controlled trial, the experimental group (n = 50) was statistically significant in preoperative evaluation time (4.51 ± 0.34 mins vs 5.43 ± 0.34 mins) and operative time (31.87 ± 5.57 mins vs 36.32 ± 5.28 mins) compared to the control group (n = 50) (P < .001). There was no significant intergroup difference in complications associated with surgery (P > .05). CONCLUSION AND RELEVANCE: The new surgical assistance aid developed in this study guides surgeons to ease the selection of surgical approaches and shorten the operative time.

Comparative proteomic analysis of dental pulp from supernumerary and normal permanent teeth.

OBJECTIVES: To obtain and compare the protein profiles of supernumerary and normal permanent dental pulp tissues. MATERIALS AND METHODS: Dental pulp tissues were obtained from supernumerary and normal permanent teeth. Proteins were extracted and analyzed by liquid chromatography-tandem mass spectrometry (LC/MS-MS). Protein identification and quantification from MS data was performed with MaxQuant. Statistical analysis was conducted using Metaboanalyst to identify differentially expressed proteins (DEPs) (P-value < 0.05, fold-change > 2). Gene Ontology enrichment analyses were performed with gProfiler. RESULTS: A total of 3,534 proteins were found in normal dental pulp tissue and 1,093 in supernumerary dental pulp tissue, with 174 DEPs between the two groups. This analysis revealed similar functional characteristics in terms of cellular component organization, cell differentiation, developmental process, and response to stimulus, alongside exclusive functions unique to normal permanent dental pulp tissues such as healing, vascular development and cell death. Upon examination of DEPs, these proteins were associated with the processes of wound healing and apoptosis. CONCLUSIONS: This study provides a comprehensive understanding of the protein profile of dental pulp tissue, including the first such profiling of supernumerary permanent dental pulp. There are functional differences between the proteomic profiles of supernumerary and normal permanent dental pulp tissue, despite certain biological similarities between the two groups. Differences in protein expression were identified, and the identified DEPs were linked to the healing and apoptosis processes. CLINICAL RELEVANCE: This discovery enhances our knowledge of supernumerary and normal permanent pulp tissue, and serves as a valuable reference for future studies on supernumerary teeth.

Investigation of the fungiform papillae number in children with tooth number anomalies.

OBJECTIVE: This cross-sectional study investigated the association between fungiform papillae (FP) numbers and tooth number anomalies in children, considering variables related to hypodontia and hyperdontia. The aim was to explore this association while adjusting for age and sex differences. MATERIALS AND METHODS: A total of 144 children (aged 8-10) were categorized into hypodontia (n = 48), hyperdontia (n = 48), and control groups (n = 48). Clinical and radiographic diagnoses were used to classify tooth number anomalies. Hypodontia was categorized by number and location, while hyperdontia was categorized by number, shape, and location. FP were assessed using the Denver Papillae Protocol. Data analyses were performed using NCSS software, with p < 0.05 considered statistically significant. RESULTS: The hypodontia group (22.5 ± 8.4) exhibited significantly lower FP than the control group (30.4 ± 9.2) and the hyperdontia group (27.9 ± 7.8) (p < 0.0005, p = 0.003, respectively). No significant difference existed between the hyperdontia and control groups. FP numbers in hypodontia subgroups showed no significant differences based on teeth agenesis numbers or locations. Similarly, hyperdontia subgroup analyses revealed no significant differences in FP numbers based on supernumerary teeth shapes (supplemental, conical, tuberculoid, paramolar) or the numbers of supernumerary teeth. CONCLUSIONS: The lower FP numbers in children with hypodontia suggested an association between teeth and FP number. However, the non-significant difference in FP numbers with hyperdontia underscored the complexity of tooth development, warranting further investigations. CLINICAL RELEVANCE: Children with hypodontia may exhibit distinct FP numbers compared to those without tooth number anomalies.

Rare Germline Variants in the Adenomatous Polyposis Coli Gene Associated with Dental and Osseous Anomalies.

APC is a tumor suppressor gene that exerts its effect through the regulation of the Wnt signaling pathway. Loss of function mutations of the gene are associated with familial adenomatous polyposis (FAP). Early diagnosis in FAP patients is essential to prevent the development of colorectal cancer. Extraintestinal manifestations often precede the formation of the polyposis; therefore, these manifestations may serve as a clinical indicator for the condition. The aim of this study was to assess genotype-phenotype associations between the location of APC mutations and various extraintestinal features, mainly focusing on osseous and dental anomalies. Analyses of our cases and the mutations available in the literature with these manifestations revealed that mutations in the N-terminal region (amino acids 1-~1000) of the protein are more frequently associated with only osseous anomalies, whereas dental manifestations are more prevalent in mutations in the middle region (amino acids 1000-~2100). In addition, supernumerary teeth were found to be the most common dental feature. Since dental abnormalities often precede intestinal polyposis, dentists have a crucial role in the early identification of patients at risk.

Treatment and genetic analysis of multiple supernumerary and impacted teeth in an adolescent patient.

BACKGROUND: Multiple supernumerary teeth, combined with numerous impacted teeth, can lead to various malocclusions, posing significant treatment challenges. While certain genes associated with syndromic cases of multiple supernumerary and impacted teeth have been identified, the etiologies of non-syndromic cases still largely remain elusive. CASE PRESENTATION: Here, we report a treatment of a 12-year-old boy who presented with 10 supernumerary teeth and 6 impacted teeth, accompanied by a genetic analysis to explore the underlying etiology. During the treatment, fifteen teeth were extracted, and various skilled techniques, including the closed-eruption technique and the application of by-pass arches, were utilized. Post-treatment, traction was successful for all the impacted teeth, without any tooth mobility or reduction in gingival height. Space closure, well-aligned teeth, and excellent functional occlusion were achieved. Furthermore, comprehensive genetic analysis was conducted through whole-exome sequencing on the patient and his parents, which revealed a potential link between the patient's numerous supernumerary teeth and abnormal mineralization. Notably, the p.Ser496Pro variant in the TCF7L2 gene was identified as a potential candidate variant in this patient. CONCLUSIONS: Overall, our findings not only report the treatment of a rare case involving multiple supernumerary and impacted teeth but also offer valuable insights into the molecular basis of supernumerary teeth.

Clinical features of non-syndromic late developing supernumerary teeth: a sign of the third dentition?

OBJECTIVES: This study aimed to summarize the clinical features of non-syndromic late developing supernumerary teeth (LDST) and comparisons with common supernumerary teeth (ST) and explore the association between LDST and the third dentition. MATERIALS AND METHODS: This study retrospected cone-beam computed tomography (CBCT) and medical history of 41,903 consecutive patients from January to December 2021. Comparisons between ST and LDST were evaluated by Chi-square test or Fisher exact test. Correlation between chronological age and dental stage age was evaluated by Spearman's rank correlation coefficient. Binary logistic regression analysis was used to explore the features of LDST originating from the third dentition. RESULTS: Sixty patients with 126 non-syndromic LDST and 1602 patients with 1988 non-syndromic ST were identified. The prevalence of ST and LDST was 3.82% and 0.14%, respectively, with a male-female ratio of 1.78:1 and 1.31:1. LDST patients mainly had LDST in multiple (58.33%) and bilaterally (41.67%), with an average of 2.1/patient. Most LDST were normal-shaped (84.13%), vertically oriented (71.43%), located in the mandible (80.16%), and distributed in the premolar region (82.54%). The study also indicated that the development of LDST was correlated with permanent teeth, with LDST developing 6.48 to 10.45 years later. In this study, 72.22% of LDST met the clinical criteria for the third dentition. CONCLUSIONS: LDST manifested different clinical features from common ST. LDST might be closely related to the third dentition. CLINICAL RELEVANCE: This work would help to comprehend LDST from a clinical perspective, and may be complementary to the criteria of the third dentition.

Management options and long-term follow-ups for permanent double incisors: six to eleven-year case reports.

BACKGROUND: Double teeth are dental anomalies that can lead to aesthetic and orthodontic problems. CASE PRESENTATION: This report discusses two cases involving the multidisciplinary management of permanent maxillary left lateral incisors fused with a supernumerary tooth in two girls aged 9 and 10. Following intraoral and radiographic examinations, one was diagnosed with fusion, and the other was diagnosed with concrescence. The crown of the fused incisor was separated using a burs and extracted intraorally. The concrescent incisor was separated along its length using a laser and intentionally replanted extraorally. After a 6-year follow-up, no pathological signs were observed in the fused incisor. However, after an 11-year follow-up, external resorption was observed in the concrescent incisor. CONCLUSIONS: Both incisors remained asymptomatic throughout the observation period. This case report highlights two different and effective methods employed to preserve the natural function, form, and aesthetics of double incisors.

Prevalence of tooth agenesis and supernumerary teeth related to different Thai cleft lip and cleft palate populations.

BACKGROUND: Pattern of dental anomalies encountered in cleft patients shows subtle signs of genetic involvement. This study aimed to evaluate the prevalence and pattern of tooth agenesis and supernumerary teeth in Thai cleft population according to the cleft type. METHODS: Data collected from patients with cleft lip and palate, who had been treated at Tawanchai Cleft Center, Khon Kaen University, Thailand, available during year 2012-2022, were investigated. Records from 194 patients with non-syndromic clefts met the inclusion criteria. Standard dental records, and at least either orthopantomogram (OPG) or cone beam computed tomography (CBCT), were examined. Statistical analysis was performed using chi-square and binominal test (p ≤ 0.05). RESULTS: Prevalence of tooth agenesis was higher (77.3%) than that of supernumerary teeth (5.7%) and was more common in bilateral cleft lip and palate (BCLP) (88.1%) than in unilateral cleft lip and palate (UCLP) (72.6%) (p = 0.017). The upper lateral incisor was more frequently affected (46.4%), followed by the upper second premolar. The number of missing teeth observed on the left side was significantly higher. Patients with left UCLP (ULCLP) had the highest prevalence of tooth agenesis. A total of 41 tooth agenesis code (TAC) patterns was found. The prevalence of supernumerary teeth was comparable with 6.6% of ULCLP, 5.1% of BCLP, and 4.5% of URCLP. Tooth-number anomalies were observed more often in the BCLP and were most likely to occur on the left side of the maxilla. Both types of anomalies could be featured in a small proportion of cleft patients. CONCLUSIONS: More than half of the patients with non-syndromic cleft lip and palate in this study, presented with tooth-number anomalies. Tooth agenesis was approximately 10-time more prevalent than supernumerary teeth. Tooth agenesis was likely to appear on the left-side of the maxilla regardless of the laterality of the cleft.

Risk prediction model of impacted supernumerary tooth-associated root resorption in children based on cone-beam computed tomography analysis: a case control study.

BACKGROUND: External surface resorption is pressure-induced resorption and occurs on the external surface of the root, pressure exerted by impacted teeth, is common causes of external surface resorption. Predictive risk factors of impacted supernumerary tooth-associated root resorption (ISTARR) mentioned in this article include supernumerary teeth and patient factors. To investigate the risk factors of impacted supernumerary tooth-associated root resorption and predict the incidence of root resorption. METHODS: This restrospective study enrolled 324 patients with impacted supernumerary tooth. All Cone-Beam Computed Tomography (CBCT) data and patient information were divided into two groups (without tooth root resorption and with root resorption). CBCT images and patient information (age and gender) of 133 patients had adjacent tooth root resorption and 191 did not. seven variables were analysed using binary logistic regression. RESULTS: Individual analysis of potential risk factors showed that age, crown mesiodistal direction, root formation, and odontotheca of the impacted supernumerary tooth were associated significantly with ISTARR. Binary logistic regression showed that impacted supernumerary tooth with odontotheca (Odd Ratio = 2.926), the crown is in the middle (Odd Ratio = 1.446), located at the middle third of the adjacent tooth root (Odd Ratio = 1.614), complete root development (Odd Ratio = 1.334), and patient's age (Odd Ratio = 1.261) were significantly associated with ISTARR risk. CONCLUSIONS: The risk factors of root resorption can be detected and predicted early according to the features of supernumerary tooth and patient's age. Still, more prospective studies with larger sample size are needed to validate the result.

Three-dimensional evaluation of dental characteristics in patients with Cleidocranial dysplasia.

BACKGROUND: Cleidocranial dysplasia (CCD) is an autosomal dominant hereditary disorder. Besides skeletal abnormalities, CCD is often associated with dental complications, such as multiple supernumerary teeth and permanent teeth impaction or delayed eruption. METHODS: Supernumerary teeth of axial, sagittal and coronal CBCT view was characterized in detail and 3D image reconstruction was performed. Number and location of teeth, morphology of supernumerary teeth, positional relationship between supernumerary and adjacent permanent teeth, direction of supernumerary teeth in CCD patients were analyzed. RESULTS: The mean age of the 3 CCD patients in this study was 16.7 years. Among 36 supernumerary teeth, the majority of them were identified as apical side located and lingual side located. Normal orientation was the most common type in this study, followed by sagittal orientation, and horizontal orientation. Horizontal orientation teeth were all distributed in the mandible. Supernumerary teeth exhibited significantly shorter crown and dental-root lengths, as well as smaller crown mesiodistal and buccolingual diameters (P < 0.01). There was no difference in the number of supernumerary teeth between the maxilla and mandible, and the premolars region had the largest number of supernumerary teeth and the incisor region had the smallest number. CONCLUSIONS: This study compares number and location of teeth, morphology of supernumerary teeth, positional relationship between supernumerary and adjacent permanent teeth and direction of supernumerary teeth, this study also provides a reference for the comprehensive evaluation of CCD patients before surgery.

Effect of maxillary anterior supernumerary tooth extraction on the underlying malocclusion.

INTRODUCTION: Orthodontic discrepancies are a common finding in patients with supernumerary teeth (ST). The presence of a ST can cause a number of orthodontic discrepancies, including delayed eruption or retention of adjacent teeth, crowding, spacing, and abnormal root formation. The aim of the present study was to assess the effect of extraction of an anterior supernumerary tooth on the underlying orthodontic discrepancies without additional treatment for a 6-month period. METHODS: This was a prospective, longitudinal, observational, study. It included 40 participants with orthodontic malocclusions due to maxillary anterior supernumeraries. We examined the changes in the crowding and excessive space in the anterior and posterior segments on cast models. RESULTS: In the group that presented with crowding, a statistically significant decrease of 0.95 ± 0.17 mm (P < 0.001) was found between T0 and T1. Of the participants, three exhibited full self-correction. The excessive space at T0 (3.06 mm) decreased by 1.78 ± 0.19 mm to T1 (1.28 mm) in the anterior segment. Seven participants showed full self-correction of the diastemas after the 6-month observation period. CONCLUSION: The results imply that orthodontic treatment can be postponed for at least 6 months after the extraction of the supernumerary tooth as potential self-correction can be expected. This natural alleviation of the malocclusions may make the orthodontic treatment simpler, shorten the treatment time and decrease overall appliance wear time.

Endodontic microsurgery and prosthodontic treatment of a permanent anterior concrescence: A case report.

Concrescence is a rare dental anomaly in which two adjacent teeth are united only by their cementum. Concrescence most frequently occurs in molars, especially a third mandibular molar and a supernumerary tooth. It is rarely seen in the maxillary anterior teeth. This case report is the first in the literature which details the successful treatment of a concrescence between the maxillary central incisor and a supernumerary tooth through multidisciplinary therapy. The treatment plan included root canal treatment, endodontic microsurgery, and prosthodontic treatment.

Globe-shaped central incisors in a patient with otodental syndrome.

Hearing impairments and dental anomalies are found in many genetic syndromes. Otodental syndrome is a rare combination of hearing loss and the presence of a pathognomonic dental phenotype known as globodontia, in which the tooth exhibits an abnormal globe shape. There is no histologic evidence of structural anomalies in the enamel, dentin, or pulp. This report describes the case of a 12-year-old boy who had hearing loss and 2 supernumerary globe-shaped teeth in the sites of the permanent maxillary central incisors. The diagnosis of otodental syndrome was established based on the clinical, radiographic, and histologic features, but other conditions, including dens evaginatus, talon cusp, dens invaginatus, and compound odontoma, should be included in the differential diagnosis. Dental treatment consisted of the extraction of both anomalous teeth, allowing spontaneous eruption of the impacted permanent central incisors. Early diagnosis of otodental syndrome permits a multidisciplinary approach to prevent other pathologic conditions, reduce functional damage, and avoid social problems.

Multidisciplinary approach to multiple dental anomalies in pediatric patients: a case report with 4-year follow-up.

The objective of this article is to report the clinical case and 4-year follow-up of a 5-year-old child with multiple dental anomalies, emphasizing the importance of early diagnosis and use of combined pediatric surgery and orthodontic approaches. A 5-year-old boy, accompanied by his mother, sought dental care for dental caries and tooth pain. Clinical and radiographic examinations revealed active caries, a supernumerary primary tooth in the region of the mandibular right second premolar, and severe ankylosis of the primary mandibular right second molar. The treatment plan involved extraction of the supernumerary tooth as well as sectioning and extraction of the ankylosed molar. When the patient was 6 years old, the permanent mandibular right first molar showed signs of an altered eruptive process, and orthodontic treatment was initiated. A unilateral band-and-loop space maintainer with coil springs designed to move the permanent first molar was placed on the primary first molar. A new panoramic radiograph, obtained when the patient was aged 7 years, suggested the presence of an odontoma in the apical region of the primary maxillary right canine. Surgical removal and histopathologic examination of the lesion confirmed that it was a developing odontoma. After surgery, due to occlusal anomalies that included transverse maxillary deficiency, deep overbite, and midline deviation, the patient underwent rapid maxillary expansion therapy with a Haas-type appliance. When the patient was 8 years old, orthodontic treatment continued with a removable palatal Hawley expander and a orthodontic mandibular lingual arch. Currently, at the age of 9 years, the child is still undergoing fixed orthodontic treatment after surgical exposure of the impacted permanent maxillary right canine and bonding of an orthodontic attachment to enable traction. A multidisciplinary approach to the management of dental anomalies promotes a favorable prognosis and ensures comprehensive treatment of young patients.

Minimally invasive surgical removal of bilateral impacted mandibular supernumerary teeth using 3D surgical guide template: a case report.

Impacted supernumerary teeth are defined as the presence of one or more teeth in a patient's upper and lower jaws in addition to the normal number of teeth in the dental arch. It has an incidence rate of approximately 1%-14% and more frequently occurs in males than females, may be single or multiple, unilateral or bilateral, erupted or impacted. In this article, we describe the case of a patient with two supernumerary teeth between the roots of the mandibular second premolar and the first molar, which influenced the effectiveness of the first orthodontic treatment. The special anatomical position of the complex supernumerary teeth made tooth extraction challenging. Given the higher risk status of surgery, we implemented a novel tooth extracting technique for this patient. Thus, in this study, we describe a case of minimally invasive extraction of bilateral mandibular impacted supernumerary teeth using a digital 3D positioning guide plate.

PREVALENCE OF DENTITION, DENTAL ARCHES AND DENTAL ANOMALIES.

Malocclusion can have a negative impact on children's quality of life. Patients with severe malocclusions tend to smile less and look for ways to improve their smile. The mentioned study was conducted in 400 patients aged 3 to 18 years, who applied to the dental clinic for orthodontic treatment regardless of age and gender. The aim of the study was the prevalence of occlusion, dental arches and dental anomalies, most often combined occlusion anomalies, functional disorders, carious and filled teeth and periodontal diseases in the examined patients. According to the results of the research, it was established that the majority of the examined patients were female. Among occlusion anomalies, occlusion class II subclass I was detected with the highest frequency. Almost 11% of the examined had a functional disturbances oral and maxillofacial system. 6% of the examined have an anomaly of the shape of the crown of the teeth. 6.25% of cases have microdontia and 5.5% have macrodontia. 1.17% showed pathological wear and 24.55 enamel hypoplasia. 1% supernumerary tooth, of which 0.75% supernumerary tooth between central incisors, 0.25% supernumerary tooth in other area. Persistent tooth in 3.25% of cases. 5% of retentive teeth are one or several teeth at the same time. 26.75% have one or more dystopian postures. Diastema was detected in 19.75%. Most of the examined patients were female, which is explained by the perception of patients and their parents regarding facial aesthetics in relation to gender. Most of the patients turn to orthodontics in cases of occlusal anomalies that are more aesthetically pronounced and easily perceived by others. In the studied society, oral health and oral care skills are given less importance, as evidenced by high rates of periodontal diseases, caries, and filled teeth. In the mentioned population, it is very important to raise the level of knowledge of the importance of oral health, which is possible by conducting educational events in kindergartens, schools, public gathering places, dental clinics.

Decoding the multifaceted signatures and transcriptomic characteristics of stem cells derived from apical papilla and dental pulp of human supernumerary teeth.

Supernumerary teeth are advantaged sources for high-quality stem cell preparation from both apical papilla (SCAP-Ss) and dental pulp (DPSCs). However, the deficiency of the systematic and detailed comparison of the biological and transcriptomic characteristics of the aforementioned stem cells largely hinders their application in regenerative medicine. Herein, we collected supernumerary teeth for SCAP-S and DPSC isolation and identification by utilizing multiple biological tests (e.g., growth curve, cell cycle and apoptosis, adipogenic and osteogenic differentiation, and quantitative real-time polymerase chain reaction). Furthermore, we took advantage of transcriptome sequencing and multifaceted bioinformatic analyses to dissect the similarities and diversities between them. In this study, we found that SCAP-Ss and DPSCs showed indistinctive signatures in morphology and immunophenotypes, whereas with diversity in cell vitality and multi-lineage differentiation as well as gene expression profiling and differentially expressed genes-associated gene ontology and signaling pathways. Collectively, our data indicated the diversity of the multifaceted signatures of human supernumerary teeth-derived stem cells both at the cellular and molecular levels, which also supplied new references for SCAP-Ss serving as splendid alternative stem cell sources for regenerative medicine purposes.

Computer-Assisted Preoperative Simulation and Augmented Reality for Extraction of Impacted Supernumerary Teeth: A Clinical Case Report of Two Cases.

Delayed eruption, malocclusion, poor oral hygiene, and formation of follicular cysts are some complications associated with an impacted supernumerary tooth (ST). Although surgical extraction is one of the methods to prevent these complications, it can also lead to fractured roots or has a risk of permanent injury to young teeth and gingiva. Recently, computer-assisted preoperative simulation has been helpful in planning the surgery for precise extraction of impacted ST guided with 3-dimensional images. Herein, we present 2 cases of extraction of severely impacted ST guided by preoperative computer-assisted simulation and intraoperative augmented reality. While being minimally invasive, the augmented reality-guided system can precisely highlight the tooth position. The therapeutic aspects of these procedures have also been discussed.

Count Me in, Count Me out: Regulation of the Tooth Number via Three Directional Developmental Patterns.

Tooth number anomalies, including hyperdontia and hypodontia, are common congenital dental problems in the dental clinic. The precise number of teeth in a dentition is essential for proper speech, mastication, and aesthetics. Teeth are ectodermal organs that develop from the interaction of a thickened epithelium (dental placode) with the neural-crest-derived ectomesenchyme. There is extensive histological, molecular, and genetic evidence regarding how the tooth number is regulated in this serial process, but there is currently no universal classification for tooth number abnormalities. In this review, we propose a novel regulatory network for the tooth number based on the inherent dentition formation process. This network includes three intuitive directions: the development of a single tooth, the formation of a single dentition with elongation of the continual lamina, and tooth replacement with the development of the successional lamina. This article summarizes recent reports on early tooth development and provides an analytical framework to classify future relevant experiments.

Rare Genetic Variants in Human APC Are Implicated in Mesiodens and Isolated Supernumerary Teeth.

The activation of Wnt/ß-catenin signalling is a prerequisite for odontogenesis. APC, a member of the AXIN-CK1-GSK3ß-APC ß-catenin destruction complex, functions to modulate Wnt/ß-catenin signalling to establish regular teeth number and positions. APC loss-of-function mutations are associated with the over-activation of WNT/ß-catenin signalling and subsequent familial adenomatous polyposis (FAP; MIM 175100) with or without multiple supernumerary teeth. The ablation of Apc function in mice also results in the constitutive activation of ß-catenin in embryonic mouse epithelium and causes supernumerary tooth formation. The objective of this study was to investigate if genetic variants in the APC gene were associated with supernumerary tooth phenotypes. We clinically, radiographically, and molecularly investigated 120 Thai patients with mesiodentes or isolated supernumerary teeth. Whole exome and Sanger sequencing identified three extremely rare heterozygous variants (c.3374T>C, p.Val1125Ala; c.6127A>G, p.Ile2043Val; and c.8383G>A, p.Ala2795Thr) in APC in four patients with mesiodentes or a supernumerary premolar. An additional patient with mesiodens was compound as heterozygous for two APC variants (c.2740T>G, p.Cys914Gly, and c.5722A>T, p.Asn1908Tyr). Rare variants in APC in our patients are likely to contribute to isolated supernumerary dental phenotypes including isolated mesiodens and an isolated supernumerary tooth.