The mammalian dentition is a serially homogeneous structure that exhibits wide numerical and morphological variation among multiple different species. Patterning of the dentition is achieved through complex reiterative molecular signaling interactions that occur throughout the process of odontogenesis. The secreted signaling molecule Sonic hedgehog (Shh) plays a key role in this process, and the Shh coreceptor growth arrest-specific 1 (Gas1) is expressed in odontogenic mesenchyme and epithelium during multiple stages of tooth development. We show that mice engineered with Gas1 loss-of-function mutation have variation in number, morphology, and size of teeth within their molar dentition. Specifically, supernumerary teeth with variable morphology are present mesial to the first molar with high penetrance, while molar teeth are characterized by the presence of both additional and absent cusps, combined with reduced dimensions and exacerbated by the presence of a supernumerary tooth. We demonstrate that the supernumerary tooth in Gas1 mutant mice arises through proliferation and survival of vestigial tooth germs and that Gas1 function in cranial neural crest cells is essential for the regulation of tooth number, acting to restrict Wnt and downstream FGF signaling in odontogenic epithelium through facilitation of Shh signal transduction. Moreover, regulation of tooth number is independent of the additional Hedgehog coreceptors Cdon and Boc, which are also expressed in multiple regions of the developing tooth germ. Interestingly, further reduction of Hedgehog pathway activity in Shh^tm6Amc hypomorphic mice leads to fusion of the molar field and reduced prevalence of supernumerary teeth in a Gas1 mutant background. Finally, we demonstrate defective coronal morphology and reduced coronal dimensions in the molar dentition of human subjects identified with pathogenic mutations in GAS1 and SHH/GAS1, suggesting that regulation of Hedgehog signaling through GAS1 is also essential for normal patterning of the human dentition.

Introduction: Aligners represent a common treatment for orthodontic patients thanks to their countless advantages including aesthetics, comfort, and oral hygiene maintenance; at the same time, they are associated with a reduced number of visits and a low incidence of complications. Although aligners have undergone considerable improvements over time, to date they have limitations in resolving the most serious malocclusions related to transverse maxillary deficiency. The aim of the present study was to retrospectively evaluate an orthodontic protocol (the Nuvola^® OP System) which associates a morpho-functional corrector (to be used for 30 min/day) with the aligner, allowing for the treatment of cases that would be difficult or unpredictable with aligners alone. Methods: Linear measurements were taken on STL files of 100 patients. In 77 patients between 18 and 55 years (mean 28.6 ± 16.2 (standard deviation) years), 3D superimpositions of the maxilla obtained from intraoral scans before and after treatment were performed in order to evaluate the degree of maxillary expansion. The normality of the data distribution was tested. The pre- and post-treatment data were compared using a paired t-test with a 5% significance level. After treatment, a questionnaire was proposed to assess patients’ degree of satisfaction and compliance. Results: A statistically significant difference (p < 0.05) for each distance evaluated was found. The maximum expansion was obtained at the first molar level (2.35 ± 1.64 mm). Of the subjects who completed the questionnaire, 96% were satisfied and 90% were able to perform the protocol without difficulty for the required duration. Conclusions: A significant expansion of the maxillary arch as well as a high degree of patient satisfaction and compliance were observed with the Nuvola^® OP System. Further studies are needed in order to clinically evaluate the relative contribution of the aligners and morpho-functional device to the obtained expansion.

The ANB angle, the cephalometric parameter of choice for assessing the anteroposterior relationship between the maxilla and mandible, is subject to several limitations, prompting the investigation of alternative parameters. Objective: This study aimed to investigate the ABwise measurement as an alternative to the ANB angle for evaluating maxillomandibular relationships in orthodontics, particularly addressing the impact of skeletal discrepancies on conventional methods. Methods: A retrospective analysis was performed on a CBCT dataset of patients attending the University of Milan’s Department of Orthodontics and Maxillofacial Surgery, selected based on high-quality imaging, a full-cranium field of view, and a slice thickness between 150 and 300 μm. Eight craniofacial landmarks were annotated using the 3D Slicer software to calculate the ANB values and the new ABwise measurement. Statistical analyses included Spearman’s correlation (ρ), linear regression, and inter-rater agreement (Cohen’s κ score), with data classified into skeletal Classes I, II, and III based on defined thresholds. Results: 354 CBCT were selected and analyzed (mean age: 18.6 years). ABwise showed a strong correlation with the ANB angle (ρ = 0.805) and new normative ranges for ABwise were established: Class I (−1.4 ± 2.3 mm), Class II (>0.9 mm), and Class III (<−3.7 mm). Moderate agreement was observed between the ABwise and ANB classifications (κ = 0.527). ABwise effectively addressed limitations associated with divergence and vertical discrepancies, providing a more reliable assessment of skeletal sagittal relationships. Conclusions: ABwise presents a viable alternative to the ANB angle for three-dimensional cephalometric analysis, offering improved accuracy and alignment with radioprotection principles by reducing the CBCT field of view needed for its measurement. Further research is required in order to validate these findings across diverse populations and clinical scenarios.

Purpose: The present study aimed to compare and correlate the ANB angle with the bisector Wits appraisal for a three-dimensional (3D) assessment of the maxillomandibular sagittal relationship using a cone beam computed tomography (CBCT) dataset. Methods: After outlier removal, 351 CBCT scans were chosen based on inclusion criteria (high quality, full-cranium field of view [FOV], slice thickness 150–300 μm) and analyzed using 3DSlicer software (Brigham and Women’s Hospital, Boston, MA, USA, version 5.2.2). Eight anatomical landmarks were manually annotated, identified on axial views, and confirmed on the rendered volume image. The coordinates of each landmark were exported and the ANB (°) and bisector–Wits (mm) measurements were constructed. Dahlberg’s D tested the intraobserver reliability and two-sample Kolmogorov–Smirnov test was executed to assess normality and to select the subsequent tests. Spearman’s rank correlation coefficient (ρ) was utilized to correlate the angular (ANB) and linear (bisector–Wits) measurements, whereas the Siegel estimator for nonparametric linear regression was employed to establish norm values by the correlation equation. Significance was set at p < 0.05 with correlation coefficients exceeding ρ > 0.70 deemed clinically relevant. Results: High (ρ = 0.773) and statistically significant ( p < 0.001) correlations between the ANB and bisector–Wits measurements were found. The obtained equation was the following: bisector–Wits = 1.06 × ANB – 6.32. Therefore, the obtained rounded norm range for bisector–Wits for skeletal class I sagittal relationship was determined to be from −6.3 to −2.1 mm (−4.2 ± 2.1 mm). Values less than −6.3 mm correspond to a class III, whereas greater than −2.1 mm correspond to a class II skeletal relationship. Conclusion: The study revealed a statistically significant correlation between the ANB and bisector–Wits. From a 3D perspective, the bisector–Wits represents a reliable parameter to assess maxilla–mandibular skeletal discrepancies instead of the ANB angle, also adhering to radioprotection principles by limiting the FOV to the maxillary complex only and potentially reducing the radiation exposure in CBCT-based cephalometry.

The position and inclination of the incisors play a crucial role in achieving optimal outcomes in orthodontic and orthognathic surgical treatment, given their impact on facial aesthetics. Background/objectives: Due to numerous distorting factors that affect the reliability of the ANB angle, the aim of the present work is to evaluate a more constant parameter over time, the anterior nasal spine (ANS), and explore whether aligning the incisal margin of the upper incisors with the anterior nasal spine could be a reliable indicator for achieving appropriate labial support in pre-surgical orthodontic preparation. Methods: From a pool of 500 cone beam computed tomography (CBCT) scans, 50 CBCT examinations displaying a Class 1 skeletal pattern (ANB = 2° ± 2°) with an intermediate (3.2–4 mm) or mixed (4–6 mm) sagittal maxillary position (MX), as determined by the 3D multiplanar total face approach (TFA), were selected and compared with CBCT examinations randomly chosen from the initial pool. Moreover, 12 landmarks were identified, and measurements were automatically obtained, using software, and recorded. Mean and standard deviation values were calculated for each sample. A comparison was made between the two samples, aligning the results with the morphological analysis of the anterior nasal spine and the sagittal position of the upper maxilla. Results: In Class 1 subjects, the distance between the incisal margin and the plane passed in relation to the anterior nasal spine should range between −1 mm and 1 mm, aligned with or slightly ahead of the anterior nasal spine or slightly ahead of this limit. Conclusions: The anterior nasal spine can serve as a reliable reference point for planning the position of the upper incisors, with excessive proclination or retroclination from this reference point deemed unacceptable.