Analyzing effects on anterior open bite in twins by PLS-SEM and sobel test.

OBJECTIVE: This study aimed to assess the different pathways between predictor factors such as zygosity, atypical swallowing, mouth breathing, breastfeeding and bottle feeding related to anterior open bite (AOB) in twins. METHODS: The study was conducted in monozygotic (MZ) and dizygotic (DZ) twin children aged 3-15 years. AOB, atypical swallowing, mouth breathing, feeding type, duration of bottle use, and mouth opening status during sleep were recorded during oral examination. Partial least squares structural equation model (PLS-SEM) and sobel tests were performed to assess the total and indirect effects among the variables on AOB. RESULTS: A total of 404 children (29.2% MZ;70.8% DZ) participated in this study. The effect of zygosity on mouth breathing in the PLS-SEM model was statistically significant. Conversely, it was determined that mouth breathing effected that atypical swallowing (p = 0.001). Atypical swallowing triggered AOB (p = 0.001). The atypical swallowing has a mediation effect between AOB and mouth breathing (p = 0.020). Mouth breathing causes atypical swallowing and therefore indirectly increases the likelihood of AOB. While breastfeeding decreases AOB incidence (p = 0.023), bottle feeding increases AOB incidence (p = 0.046). The sobel tests show that the fully mediator variable feature of mouth breathing is statistically significant in the negative relation between zygosity and atypical swallowing. CONCLUSION: The PLS-SEM model showed that mouth breathing triggers atypical swallowing and atypical swallowing triggers AOB. As a result of this chain of relationships, an indirect effect of zygosity on AOB was observed. According to sobel tests, zygosity has an indirect effect on atypical swallowing through mouth breathing, while mouth breathing has a positive indirect effect on AOB through atypical swallowing. CLINICAL RELEVANCE: This study identified the relationships between different factors and the presence of AOB. The findings of this study demonstrate in detail the relationships between AOB and zygosity, atypical swallowing, mouth breathing, breastfeeding and bottle feeding. Brestfeeding has a reducing effect on the frequency of AOB. Among the nutritional forms, breastfeeding ensures the proper development of the stomatognathic system by working the oro-facial muscles.

Deep learning for virtual orthodontic bracket removal: tool establishment and application.

OBJECTIVE: We aimed to develop a tool for virtual orthodontic bracket removal based on deep learning algorithms for feature extraction from bonded teeth and to demonstrate its application in a bracket position assessment scenario. MATERIALS AND METHODS: Our segmentation network for virtual bracket removal was trained using dataset A, containing 978 bonded teeth, 20 original teeth, and 20 brackets generated by scanners. The accuracy and segmentation time of the network were tested by dataset B, which included an additional 118 bonded teeth without knowing the original tooth morphology. This tool was then applied for bracket position assessment. The clinical crown center, bracket center, and orientations of separated teeth and brackets were extracted for analyzing the linear distribution and angular deviation of bonded brackets. RESULTS: This tool performed virtual bracket removal in 2.9 ms per tooth with accuracies of 98.93% and 97.42% (P < 0.01) in datasets A and B, respectively. The tooth surface and bracket characteristics were extracted and used to evaluate the results of manually bonded brackets by 49 orthodontists. Personal preferences for bracket angulation and bracket distribution were displayed graphically and tabularly. CONCLUSIONS: The tool's efficiency and precision are satisfactory, and it can be operated without original tooth data. It can be used to display the bonding deviation in the bracket position assessment scenario. CLINICAL SIGNIFICANCE: With the aid of this tool, unnecessary bracket removal can be avoided when evaluating bracket positions and modifying treatment plans. It has the potential to produce retainers and orthodontic devices prior to tooth debonding.

Craniofacial morphology and growth in Muenke syndrome, Saethre-Chotzen syndrome, and TCF12-related craniosynostosis.

OBJECTIVES: To determine whether the midface of patients with Muenke syndrome, Saethre-Chotzen syndrome, or TCF12-related craniosynostosis is hypoplastic compared to skeletal facial proportions of a Dutch control group. MATERIAL AND METHODS: We included seventy-four patients (43 patients with Muenke syndrome, 22 patients with Saethre-Chotzen syndrome, and 9 patients with TCF12-related craniosynostosis) who were referred between 1990 and 2020 (age range 4.84 to 16.83 years) and were treated at the Department of Oral Maxillofacial Surgery, Special Dental Care and Orthodontics, Children's Hospital Erasmus University Medical Center, Sophia, Rotterdam, the Netherlands. The control group consisted of 208 healthy children. RESULTS: Cephalometric values comprising the midface were decreased in Muenke syndrome (ANB: ß = -1.87, p = 0.001; and PC1: p < 0,001), Saethre-Chotzen syndrome (ANB: ß = -1.76, p = 0.001; and PC1: p < 0.001), and TCF12-related craniosynostosis (ANB: ß = -1.70, p = 0.015; and PC1: p < 0.033). CONCLUSIONS: In this study, we showed that the midface is hypoplastic in Muenke syndrome, Saethre-Chotzen syndrome, and TCF12-related craniosynostosis compared to the Dutch control group. Furthermore, the rotation of the maxilla and the typical craniofacial buildup is significantly different in these three craniosynostosis syndromes compared to the controls. CLINICAL RELEVANCE: The maxillary growth in patients with Muenke syndrome, Saethre-Chotzen syndrome, or TCF12-related craniosynostosis is impaired, leading to a deviant dental development. Therefore, timely orthodontic follow-up is recommended. In order to increase expertise and support treatment planning by medical and dental specialists for these patients, and also because of the specific differences between the syndromes, we recommend the management of patients with Muenke syndrome, Saethre-Chotzen syndrome, or TCF12-related craniosynostosis in specialized multidisciplinary teams.

Fusion of intra-oral scans in cone-beam computed tomography scans.

PURPOSE: The purpose of this study was to evaluate the clinical accuracy of the fusion of intra-oral scans in cone-beam computed tomography (CBCT) scans using two commercially available software packages. MATERIALS AND METHODS: Ten dry human skulls were subjected to structured light scanning, CBCT scanning, and intra-oral scanning. Two commercially available software packages were used to perform fusion of the intra-oral scans in the CBCT scan to create an accurate virtual head model: IPS CaseDesigner® and OrthoAnalyzer™. The structured light scanner was used as a gold standard and was superimposed on the virtual head models, created by IPS CaseDesigner® and OrthoAnalyzer™, using an Iterative Closest Point algorithm. Differences between the positions of the intra-oral scans obtained with the software packages were recorded and expressed in six degrees of freedom as well as the inter- and intra-observer intra-class correlation coefficient. RESULTS: The tested software packages, IPS CaseDesigner® and OrthoAnalyzer™, showed a high level of accuracy compared to the gold standard. The accuracy was calculated for all six degrees of freedom. It was noticeable that the accuracy in the cranial/caudal direction was the lowest for IPS CaseDesigner® and OrthoAnalyzer™ in both the maxilla and mandible. The inter- and intra-observer intra-class correlation coefficient showed a high level of agreement between the observers. CLINICAL RELEVANCE: IPS CaseDesigner® and OrthoAnalyzer™ are reliable software packages providing an accurate fusion of the intra-oral scan in the CBCT. Both software packages can be used as an accurate fusion tool of the intra-oral scan in the CBCT which provides an accurate basis for 3D virtual planning.

The application and accuracy of feature matching on automated cephalometric superimposition.

BACKGROUND: The aim of this study was to establish a computer-aided automated method for cephalometric superimposition and to evaluate the accuracy of this method based on free-hand tracing. METHODS: Twenty-eight pairs of pre-treatment (T1) and post-treatment (T2) cephalograms were selected. Structural superimpositions of the anterior cranial base, maxilla and mandible were independently completed by three operators performing traditional hand tracing methods and by computerized automation using the feature matching algorithm. To quantitatively evaluate the differences between the two methods, the hand superimposed patterns were digitized. After automated and hand superimposition of T2 cephalograms to T1 cephalometric templates, landmark distances between paired automated and hand T2 cephalometric landmarks were measured. Differences in hand superimposition among the operators were also calculated. RESULTS: The T2 landmark differences in hand tracing between the operators ranged from 0.61 mm to 1.65 mm for the three types of superimposition. There were no significant differences in accuracy between hand and automated superimposition (p > 0.05). CONCLUSIONS: Computer-aided cephalometric superimposition provides comparably accurate results to those of traditional hand tracing and will provide a powerful tool for academic research.

In vivo reliability of 3D cephalometric landmark determination on magnetic resonance imaging: a feasibility study.

OBJECTIVE: 3D cephalometric analysis performed on cone-beam or multi-slice computed tomography (CBCT, MSCT) has superior diagnostic value compared to 2D cephalometry based on radiographs. However, this comes at the expense of increased radiation risks for the predominantly young patients. Magnetic resonance imaging (MRI) has the potential to overcome this diagnostic dilemma but has not been established for 3D cephalometry so far. Since landmark reliability forms the basis for 3D cephalometry, we evaluated the in vivo reliability of established 3D landmarks using MRI. MATERIALS AND METHODS: Sixteen orthodontic patients underwent MRI at 3 Tesla using a 0.5 mm 3D sequence. On each MRI scan, 44 cephalometric landmarks were determined. Image analysis was performed twice by two independent observers. Intra- and inter-rater agreement was assessed by mean measurement errors and intraclass correlation coefficients (ICCs). Measurement errors were calculated as Euclidean distances and distances for x-, y-, and z-coordinates. RESULTS: Overall, MRI-based 3D cephalometric landmarks revealed a high reliability comparable to prior in vivo studies using CBCT/MSCT. Intra- and inter-rater ICCs were consistently higher than 0.9. Intra-rater comparisons showed mean measurement differences (ranges) of 0.87 mm (0.41-1.63) for rater I and 0.94 mm (0.49-1.28) for rater II. Average inter-rater difference was 1.10 mm (0.52-2.29). Distinct differences in reliability between the various landmarks were observed, corresponding well with the landmarks' specific shapes. CONCLUSIONS: The present study demonstrates that MRI enables reliable determination of 3D cephalometric landmarks in vivo. CLINICAL RELEVANCE: This study emphasizes the potential of MRI to perform treatment planning and monitoring in orthodontics as well as oral and maxillofacial surgery without radiation exposure.

Automated cephalometric landmark detection with confidence regions using Bayesian convolutional neural networks.

BACKGROUND: Despite the integral role of cephalometric analysis in orthodontics, there have been limitations regarding the reliability, accuracy, etc. of cephalometric landmarks tracing. Attempts on developing automatic plotting systems have continuously been made but they are insufficient for clinical applications due to low reliability of specific landmarks. In this study, we aimed to develop a novel framework for locating cephalometric landmarks with confidence regions using Bayesian Convolutional Neural Networks (BCNN). METHODS: We have trained our model with the dataset from the ISBI 2015 grand challenge in dental X-ray image analysis. The overall algorithm consisted of a region of interest (ROI) extraction of landmarks and landmarks estimation considering uncertainty. Prediction data produced from the Bayesian model has been dealt with post-processing methods with respect to pixel probabilities and uncertainties. RESULTS: Our framework showed a mean landmark error (LE) of 1.53 ± 1.74 mm and achieved a successful detection rate (SDR) of 82.11, 92.28 and 95.95%, respectively, in the 2, 3, and 4 mm range. Especially, the most erroneous point in preceding studies, Gonion, reduced nearly halves of its error compared to the others. Additionally, our results demonstrated significantly higher performance in identifying anatomical abnormalities. By providing confidence regions (95%) that consider uncertainty, our framework can provide clinical convenience and contribute to making better decisions. CONCLUSION: Our framework provides cephalometric landmarks and their confidence regions, which could be used as a computer-aided diagnosis tool and education.

Deviating dental arch morphology in mild coronal craniosynostosis syndromes.

OBJECTIVES: To determine whether the intramaxillary relationship of patients with Muenke syndrome and Saethre-Chotzen syndrome or TCF12-related craniosynostosis are systematically different than those of a control group. MATERIAL AND METHODS: Forty-eight patients (34 patients with Muenke syndrome, 8 patients with Saethre-Chotzen syndrome, and 6 patients with TCF12-related craniosynostosis) born between 1982 and 2010 (age range 4.84 to 16.83 years) that were treated at the Department of Oral Maxillofacial Surgery, Special Dental Care and Orthodontics, Children's Hospital Erasmus University Medical Center, Sophia, Rotterdam, the Netherlands, were included. Forty-seven syndromic patients had undergone one craniofacial surgery according to the craniofacial team protocol. The dental arch measurements intercanine width (ICW), intermolar width (IMW), arch depth (AD), and arch length (AL) were calculated. The control group existed of 329 nonsyndromic children. RESULTS: All dental arch dimensions in Muenke (ICW, IMW, AL, p < 0.001, ADmax, p = 0.008; ADman, p = 0.002), Saethre-Chotzen syndrome, or TCF12-related craniosynostosis patients (ICWmax, p = 0.005; ICWman, IMWmax, AL, p < 0.001) were statistically significantly smaller than those of the control group. CONCLUSIONS: In this study, we showed that the dental arches of the maxilla and the mandible of patients with Muenke syndrome and Saethre-Chotzen syndrome or TCF12-related craniosynostosis are smaller compared to those of a control group. CLINICAL RELEVANCE: To gain better understanding of the sutural involvement in the midface and support treatment capabilities of medical and dental specialists in these patients, we suggest the concentration of patients with Muenke and Saethre-Chotzen syndromes or TCF12-related craniosynostosis in specialized teams for a multi-disciplinary approach and treatment.

Artificial Intelligence in Orthodontics: Critical Review.

With increasing digitalization in orthodontics, certain orthodontic manufacturing processes such as the fabrication of indirect bonding trays, aligner production, or wire bending can be automated. However, orthodontic treatment planning and evaluation remains a specialist's task and responsibility. As the prediction of growth in orthodontic patients and response to orthodontic treatment is inherently complex and individual, orthodontists make use of features gathered from longitudinal, multimodal, and standardized orthodontic data sets. Currently, these data sets are used by the orthodontist to make informed, rule-based treatment decisions. In research, artificial intelligence (AI) has been successfully applied to assist orthodontists with the extraction of relevant data from such data sets. Here, AI has been applied for the analysis of clinical imagery, such as automated landmark detection in lateral cephalograms but also for evaluation of intraoral scans or photographic data. Furthermore, AI is applied to help orthodontists with decision support for treatment decisions such as the need for orthognathic surgery or for orthodontic tooth extractions. One major challenge in current AI research in orthodontics is the limited generalizability, as most studies use unicentric data with high risks of bias. Moreover, comparing AI across different studies and tasks is virtually impossible as both outcomes and outcome metrics vary widely, and underlying data sets are not standardized. Notably, only few AI applications in orthodontics have reached full clinical maturity and regulatory approval, and researchers in the field are tasked with tackling real-world evaluation and implementation of AI into the orthodontic workflow.

Single-cell sequencing decodes the secrets of the RAP phenomenon of corticotomy.

Introduction: Corticotomy-assisted tooth movement is commonly performed in clinics, however, its time-limited efficacy and the fear of surgery among patients significantly limit its clinical application. Hence, researchers have investigated non-invasive methods to accelerate tooth movement. However, the molecular mechanisms underlying corticotomy-assisted tooth movement are not fully understood. Methods: Micro-CT and TRAP stain were used to tooth movement and bone resorption. Single-cell RNA sequencing was used to study the transcriptome heterogeneity of macrophages after corticotomy. Transmission electron microscopy and iron ion detection was used to evaluate ferroptosis and iron metabolism. In addition, we carried out immunohistochemistry, quantitative real-time and flow cytometry verify the effect of iron on macrophage polarization. Results: Single-cell RNA sequencing of digested alveolar bone identified a significant increase in iron metabolism-related genes post-corticotomy. Macrophages play a central role in this field. Following the dimensionality reduction of macrophages, we revealed a new developmental state via pseudotime analysis post-corticotomy. SCENIC analysis revealed that Atf3 is a key transcription factor influencing this new state. We found that Atf3+ macrophages were closely associated with osteoclasts. Moreover, cell chat revealed an increase in cellular communication between Atf3+ macrophages and other cell types after corticotomy. Discussion: These findings suggested that Atf3+ macrophages might play a key role in corticotomy-accelerated tooth movement, thus providing potential targets for drug development.

Association between the Obstructive Sleep Apnea and Cephalometric Parameters in Teenagers.

BACKGROUND: OSA is a common problem in children and adolescents. Angle class II malocclusion, a tendency toward the vertical type of growth, causes a decrease in the volume of the oral air space, increasing the risk of OSAS. The aim of this study was to evaluate the relationship between cephalometric and OSA parameters, to develop collaborative approaches between orthodontists and somnologists in the treatment of adolescents with OSA. METHODS: We analyzed data from 41 adolescents with OSA. Their mean age was 15.8 ± 1.08 years. Orthodontic and polysomnographic examinations of patients were conducted. Statistical analysis was performed in SPSS 19.0.0. RESULTS: Most often in patients with distal occlusion, a violation of the harmony in the development of the dental system was observed. The sagittal incisive fissure, characteristic of a distal occlusion, was absent due to the palatal inclination of the upper incisors in 25 (60.98%) patients. The SNB was 79.4 ± 3.1°, indicating a distal position of the mandible relative to the anterior cranial base. The SNA exceeded the normal value, which is one of the prerequisites for mandibular retrognathia. The ANB angle was 4.3 ± 1.9°. Tonsillar hypertrophy affected 6 patients, 21 had adenoid hypertrophy, and 3 had both of them. Movements of the masticatory muscles during sleep were recorded in 22.0% of patients. CONCLUSION: To improve the quality of diagnosis and treatment of OSA, a multidisciplinary approach is needed that will correct the processes of child growth and development.

Adolescent and Parent Preferences for Hypodontia: Discrete Choice Experiment.

Choosing hypodontia treatment requires young people and parents to consider a large amount of information, identify what is important to them, and make trade-offs between options. This study aimed to examine young people and parents' preferences for hypodontia treatment using discrete choice experiment (DCE). This was a cross-sectional survey of young people (12-16 y) with hypodontia of any severity, at any stage of treatment, and their parents. Participants were recruited from NHS Hospitals in England and Wales. A bespoke DCE questionnaire was developed to measure preferences for 6 attributes of hypodontia treatment (waiting time, treatment time, problems during treatment, discomfort during treatment, bite, appearance). The questionnaire was completed 1) online by young people and parents, individually or together, and 2) by child-parent dyads under observation. Preferences were analyzed using regression models. In total, 204 participants (122 young people, 56 parents, 26 dyads) completed the online questionnaire and 15 child-parent dyads completed the questionnaire under observation. The most important attribute in hypodontia treatment was improvement in appearance, but significant heterogeneity was found in preferences. Four distinct groups of participants were found: group 1 (39%): severe discomfort and problems were most important; group 2 (31%): most concerned about improvement in appearance of teeth and improvement in bite; group 3 (22%): appearance 3 times more important than any other attribute; and group 4 (9%): preferences difficult to interpret. There was variation in how child-parent dyads approached decision-making, with some negotiating joint preferences, while for others, one individual dominated. Making trade-offs in DCE tasks helped some people think about treatment and identify their preferences. Appearance is an important outcome from hypodontia treatment, but preferences vary and potential risks and functional outcome are also important to some people. There is a notable level of uncertainty in decision-making, which suggests further shared decision support would be valuable.

Automatic Masseter Muscle Accurate Segmentation from CBCT Using Deep Learning-Based Model.

Segmentation of the masseter muscle (MM) on cone-beam computed tomography (CBCT) is challenging due to the lack of sufficient soft-tissue contrast. Moreover, manual segmentation is laborious and time-consuming. The purpose of this study was to propose a deep learning-based automatic approach to accurately segment the MM from CBCT under the refinement of high-quality paired computed tomography (CT). Fifty independent CBCT and 42 clinically hard-to-obtain paired CBCT and CT were manually annotated by two observers. A 3D U-shape network was carefully designed to segment the MM effectively. Manual annotations on CT were set as the ground truth. Additionally, an extra five CT and five CBCT auto-segmentation results were revised by one oral and maxillofacial anatomy expert to evaluate their clinical suitability. CBCT auto-segmentation results were comparable to the CT counterparts and significantly improved the similarity with the ground truth compared with manual annotations on CBCT. The automatic approach was more than 332 times shorter than that of a human operation. Only 0.52% of the manual revision fraction was required. This automatic model could simultaneously and accurately segment the MM structures on CBCT and CT, which can improve clinical efficiency and efficacy, and provide critical information for personalized treatment and long-term follow-up.

Three-dimensional palatal anatomic characteristics' correlation with dermatoglyphic heterogeneity in Angle malocclusions.

OBJECTIVES: To assess correlation of dermatoglyphic (DG) pattern with quantitative palatal anatomic parameters measured using three-dimensional (3D) scanning of dental casts and to explore the possibility of utilizing these to predict future occurrence of malocclusion. MATERIALS AND METHODS: Pretreatment casts of 477 Saudi Arabian patients were divided into Class I, II, and III malocclusion groups. Fingerprints were recorded for all hand digits using a digital biometric device. Maxillary arch analysis was accomplished including intercanine, intermolar distance, palatal height, and palatal area. The results were statistically analyzed. RESULTS: The mean surface area of the palate was highest in Class II malocclusion. The DG pattern was not significantly associated with the type of malocclusion, except in the instance of the double loop characteristic (P = .05). There was a strong correlation, however, between DG characteristics like simple arch, loop, and double loop and palatal dimensions (intercanine, intermolar distance, and palatal height). Heterogeneity of DG pattern could be reliably used to predict palatal dimensions. Logistic regression revealed that only tented arch, symmetrical, spiral DG patterns and palatal area were significant but weak predictors of Angle malocclusion (P < .05). CONCLUSIONS: A novel correlation of DG pattern with 3D palatal anatomic characteristics was assessed in different Angle malocclusion classes. Few of the DG characteristics and palatal dimensions showed significant correlations. However, only some of these were significant predictors of Angle malocclusion.

Evolution of Aesthetic Dentistry.

One of the main goals of dental treatment is to mimic teeth and design smiles in a most natural and aesthetic manner, based on the individual and specific needs of the patient. Possibilities to reach that goal have significantly improved over the last decade through new and specific treatment modalities, steadily enhanced and more aesthetic dental materials, and novel techniques and technologies. This article gives an overview of the evolution of aesthetic dentistry over the past 100 y from a historical point of view and highlights advances in the development of dental research and clinical interventions that have contributed the science and art of aesthetic dentistry. Among the most noteworthy advancements over the past decade are the establishment of universal aesthetic rules and guidelines based on the assessment of natural aesthetic parameters, anatomy, and physiognomy; the development of tooth whitening and advanced restorative as well as prosthetic materials and techniques, supported by the pioneering discovery of dental adhesion; the significant progress in orthodontics and periodontal as well as oral and maxillofacial surgery; and, most recently, the implementation of digital technologies in the 3-dimensional planning and realization of truly natural, individual, and aesthetic smiles. In the future, artificial intelligence and machine learning will likely lead to automation of aesthetic evaluation, smile design, and treatment-planning processes.

Identification and Functional Studies of MYO1H for Mandibular Prognathism.

Mandibular prognathism (MP) is regarded as a craniofacial deformity resulting from the combined effects of environmental and genetic factors, while the genetically predetermined component is considered to play an important role to develop MP. Although linkage and association studies for MP have identified multiple strongly associated regions and genes, the causal genes and variants responsible for the deformity remain largely undetermined. To address this, we performed targeted sequencing of 396 genes selected from previous studies as well as genes and pathways related with craniofacial development as primary candidates in 199 MP cases and 197 controls and carried out a series of statistical and functional analyses. A nonsynonymous common variant of MYO1H rs3825393, C>T, p.Pro1001Leu, was identified to be significantly associated with MP. During zebrafish embryologic development, expression of MYO1H orthologous genes were detected at mandibular jaw. Furthermore, jaw cartilage defects were observed in zebrafish knockdown models. Collectively, these data demonstrate that MYO1H is required for proper jaw growth and contributes to MP pathogenesis, expanding our knowledge of the genetic basis of MP.

The ADAMTS1 Gene Is Associated with Familial Mandibular Prognathism.

Mandibular prognathism is a facial skeletal malocclusion. Until now, the genetic mechanism has been unclear. The goal of this study was to identify candidate genes or genomic regions directly associated with mandibular prognathism development, by employing whole genome sequencing. A large Chinese family was recruited, composed of 9 affected and 12 unaffected individuals, and the inheritance pattern of this family tends to be autosomal dominant. A single-nucleotide missense mutation in the ADAMTS1 gene (c. 742I>T) was found to segregate in the family, given that the affected individuals must be heterozygous for the mutation. For mutation validation, we screened this candidate mutation and 15 tag single-nucleotide polymorphisms in the coding sequence of ADAMTS1 among 230 unrelated cases and 196 unrelated controls using Sequenom Massarray and found that 3 in 230 cases carried this mutation and none of the controls did. Final results suggested that 2 single-nucleotide polymorphisms (rs2738, rs229038) of ADAMTS1 were significantly associated with mandibular prognathism.