Developing the Benchmark: Establishing a Gold Standard for the Evaluation of AI Caries Diagnostics.

Background/Objectives: The aim of this study was to establish a histology-based gold standard for the evaluation of artificial intelligence (AI)-based caries detection systems on proximal surfaces in bitewing images. Methods: Extracted human teeth were used to simulate intraoral situations, including caries-free teeth, teeth with artificially created defects and teeth with natural proximal caries. All 153 simulations were radiographed from seven angles, resulting in 1071 in vitro bitewing images. Histological examination of the carious lesion depth was performed twice by an expert. A total of thirty examiners analyzed all the radiographs for caries. Results: We generated in vitro bitewing images to evaluate the performance of AI-based carious lesion detection against a histological gold standard. All examiners achieved a sensitivity of 0.565, a Matthews correlation coefficient (MCC) of 0.578 and an area under the curve (AUC) of 76.1. The histology receiver operating characteristic (ROC) curve significantly outperformed the examiners' ROC curve (p < 0.001). All examiners distinguished induced defects from true caries in 54.6% of cases and correctly classified 99.8% of all teeth. Expert caries classification of the histological images showed a high level of agreement (intraclass correlation coefficient (ICC) = 0.993). Examiner performance varied with caries depth (p ≤ 0.008), except between E2 and E1 lesions (p = 1), while central beam eccentricity, gender, occupation and experience had no significant influence (all p ≥ 0.411). Conclusions: This study successfully established an unbiased dataset to evaluate AI-based caries detection on bitewing surfaces and compare it to human judgement, providing a standardized assessment for fair comparison between AI technologies and helping dental professionals to select reliable diagnostic tools.

Assessment of the quality of different commercial providers using artificial intelligence for automated cephalometric analysis compared to human orthodontic experts.

PURPOSE: The aim of this investigation was to evaluate the accuracy of various skeletal and dental cephalometric parameters as produced by different commercial providers that make use of artificial intelligence (AI)-assisted automated cephalometric analysis and to compare their quality to a gold standard established by orthodontic experts. METHODS: Twelve experienced orthodontic examiners pinpointed 15 radiographic landmarks on a total of 50 cephalometric X­rays. The landmarks were used to generate 9 parameters for orthodontic treatment planning. The "humans' gold standard" was defined by calculating the median value of all 12 human assessments for each parameter, which in turn served as reference values for comparisons with results given by four different commercial providers of automated cephalometric analyses (DentaliQ.ortho [CellmatiQ GmbH, Hamburg, Germany], WebCeph [AssembleCircle Corp, Seongnam-si, Korea], AudaxCeph [Audax d.o.o., Ljubljana, Slovenia], CephX [Orca Dental AI, Herzliya, Israel]). Repeated measures analysis of variances (ANOVAs) were calculated and Bland-Altman plots were generated for comparisons. RESULTS: The results of the repeated measures ANOVAs indicated significant differences between the commercial providers' predictions and the humans' gold standard for all nine investigated parameters. However, the pairwise comparisons also demonstrate that there were major differences among the four commercial providers. While there were no significant mean differences between the values of DentaliQ.ortho and the humans' gold standard, the predictions of AudaxCeph showed significant deviations in seven out of nine parameters. Also, the Bland-Altman plots demonstrate that a reduced precision of AI predictions must be expected especially for values attributed to the inclination of the incisors. CONCLUSION: Fully automated cephalometric analyses are promising in terms of timesaving and avoidance of individual human errors. At present, however, they should only be used under supervision of experienced clinicians.

Subjective perception of craniofacial growth asymmetries in patients with deformational plagiocephaly.

OBJECTIVES: The present investigation aimed to evaluate the subjective perception of deformational cranial asymmetries by different observer groups and to compare these subjective perceptions with objective parameters. MATERIALS AND METHODS: The 3D datasets of ten infants with different severities of deformational plagiocephaly (DP) were presented to 203 observers, who had been subdivided into five different groups (specialists, pediatricians, medical doctors (not pediatricians), parents of infants with DP, and laypersons). The observers rated their subjective perception of the infants' cranial asymmetries using a 4-point Likert-type scale. The ratings from the observer groups were compared with one another using a multilevel modelling linear regression analysis and were correlated with four commonly used parameters to objectively quantify the cranial asymmetries. RESULTS: No significant differences were found between the ratings of the specialists and those of the parents of infants with DP, but both groups provided significantly more asymmetric ratings than did pediatricians, medical doctors, or laypersons. Moreover, the subjective perception of cranial asymmetries correlated significantly with commonly used parameters for objectively quantifying cranial asymmetries. CONCLUSIONS: Our results demonstrate that different observer groups perceive the severity of cranial asymmetries differently. Pediatricians' more moderate perception of cranial asymmetries may reduce the likelihood of parents to seek therapeutic interventions for their infants. Moreover, we identified some objective symmetry-related parameters that correlated strongly with the observers' subjective perceptions. CLINICAL RELEVANCE: Knowledge about these findings is important for clinicians when educating parents of infants with DP about the deformity.

Characteristic dental pattern with hypodontia and short roots in Fraser syndrome.

Fraser syndrome (FS) is a rare autosomal recessive multiple congenital malformation syndrome characterized by cryptophthalmos, cutaneous syndactyly, renal agenesis, ambiguous genitalia, and laryngotracheal anomalies. It is caused by biallelic mutations of FRAS1, FREM2, and GRIP1 genes, encoding components of a protein complex that mediates embryonic epithelial-mesenchymal interactions. Anecdotal reports have described abnormal orodental findings in FS, but no study has as yet addressed the orodental findings of FS systematically. We reviewed dental radiographs of 10 unrelated patients with FS of different genetic etiologies. Dental anomalies were present in all patients with FS and included hypodontia, dental crowding, medial diastema, and retained teeth. A very consistent pattern of shortened dental roots of most permanent teeth as well as altered length/width ratio with shortened dental crowns of upper incisors was also identified. These findings suggest that the FRAS1-FREM complex mediates critical mesenchymal-epithelial interactions during dental crown and root development. The orodental findings of FS reported herein represent a previously underestimated manifestation of the disorder with significant impact on orodental health for affected individuals. Integration of dentists and orthodontists into the multidisciplinary team for management of FS is therefore recommended.

Craniofacial growth in infants with deformational plagiocephaly: does prematurity affect the duration of head orthosis therapy and the extent of the reduction in asymmetry during treatment?

OBJECTIVE: Although prematurity is a risk factor for developing deformational plagiocephaly (DP), to our knowledge, there are no studies that have analyzed the impact of a premature birth on the duration of head orthosis therapy and the extent of the reduction in asymmetry during treatment. MATERIALS AND METHODS: We examined 239 patients with DP who were undergoing head orthosis therapy. Depending on the gestational age, they were assigned to either a premature (gestational age of < 37 weeks) or a full-term (gestational age of ≥ 37 weeks) group. Head shape was analyzed using 3D-stereophotogrammetry at the start and end of treatment. We performed multiple linear regression analyses to evaluate the impact of prematurity on the duration of therapy and the extent of the reduction in asymmetry, taking age and the initial asymmetry of an infant's head into account. RESULTS: Head orthosis therapy led to a significant reduction in asymmetry in both groups. Using multiple linear regression analyses, we demonstrated that age at the start of treatment, the initial asymmetry and prematurity, significantly influenced the duration of therapy. Patients who were born at an earlier gestational age experienced a shorter treatment length. However, prematurity did not affect the extent of the reduction in cranial asymmetry that was achieved. CONCLUSIONS: Along with age at the start of treatment and the initial asymmetry, prematurity is significantly correlated with the duration of head orthosis therapy, but not with the extent of the reduction in asymmetry achieved. CLINICAL RELEVANCE: Knowledge of these findings is important for clinicians when planning treatment and discussing the effectiveness of head orthosis therapy with the parents of premature infants with DP.

Artificial intelligence in orthodontics : Evaluation of a fully automated cephalometric analysis using a customized convolutional neural network.

PURPOSE: The aim of this investigation was to create an automated cephalometric X­ray analysis using a specialized artificial intelligence (AI) algorithm. We compared the accuracy of this analysis to the current gold standard (analyses performed by human experts) to evaluate precision and clinical application of such an approach in orthodontic routine. METHODS: For training of the network, 12 experienced examiners identified 18 landmarks on a total of 1792 cephalometric X­rays. To evaluate quality of the predictions of the AI, both AI and each examiner analyzed 12 commonly used orthodontic parameters on a basis of 50 cephalometric X­rays that were not part of the training data for the AI. Median values of the 12 examiners for each parameter were defined as humans' gold standard and compared to the AI's predictions. RESULTS: There were almost no statistically significant differences between humans' gold standard and the AI's predictions. Differences between the two analyses do not seem to be clinically relevant. CONCLUSIONS: We created an AI algorithm able to analyze unknown cephalometric X­rays at almost the same quality level as experienced human examiners (current gold standard). This study is one of the first to successfully enable implementation of AI into dentistry, in particular orthodontics, satisfying medical requirements.

Impact of specific orthodontic parameters on the oral health-related quality of life in children and adolescents : A prospective interdisciplinary, multicentre, cohort study.

PURPOSE: The aim of the present study was to analyse the impact of specific orthodontic findings on oral health-related quality of life (OHRQoL) when taking into consideration age and psychological factors in children and adolescents. METHODS: In all, 250 children and adolescents with an indication for orthodontic diagnostics were recruited using a multicentre study design. Using validated and internationally acknowledged questionnaires, we assessed OHRQoL, health-related quality of life (HRQoL), self-esteem and behavioural problems. We also examined a selection of specific orthodontic findings using photos, model casts and cephalometric analyses, and investigated the impact of these parameters on OHRQoL using simple linear regression analyses. Thereafter, we added all the significant specific orthodontic and psychological parameters to a multiple linear regression model using a stepwise forwards selection procedure. RESULTS: We were able to identify different specific orthodontic findings that have a significant impact on OHRQoL. These were the type of lip closure, the position of the chin, the Little-index of the upper jaw, the overjet, the overbite and the ANB angle. Moreover, we were able to demonstrate that psychological and some specific orthodontic parameters have a significant impact on OHRQoL. CONCLUSION: Specific orthodontic findings have a significant impact on patients' perceived OHRQoL. Further longitudinal studies are required to investigate whether the treatment and correction of these malocclusions also improve the OHRQoL of children and adolescents.

Interest in orthodontic tooth alignment in adult patients affected by periodontitis: A questionnaire-based cross-sectional pilot study.

BACKGROUND: Orthodontic treatment can successfully align pathologically migrated teeth and lead to improvement of periodontal stability in patients with periodontitis. Periodontic-orthodontic approaches have gained increasing attention in the past years. Here, we investigated the interest of adults affected by chronic periodontitis in undergoing orthodontic treatment as well as patient-related and tooth-related influence factors. METHODS: Periodontal and orthodontic measurements/indices were taken from 115 adult patients with moderate-to-severe periodontitis. The study participants answered a questionnaire investigating patient demographics, quality of life aspects, and their interest in undergoing orthodontic treatment. Correlations between clinical data, questionnaire responses, and this interest were analyzed by means of an age- and sex-adjusted multiple regression model. RESULTS: Two-thirds of the participants were interested in orthodontic therapy and indicated long-term healthy and esthetically appealing teeth as their main motives. A significant correlation was found between subjectively felt impaired dental esthetics and an interest in orthodontic treatment. However, there were no correlations with the severity of periodontitis, tooth alignment, or patient demographics, including sex. Older patients were significantly more often interested in orthodontic treatment. Most participants had never been provided with information about orthodontic treatment options for adults. CONCLUSIONS: A considerable number of adult patients with periodontitis were interested in orthodontics to improve tooth alignment. However, severity of periodontitis and tooth misalignment or demographic factors may not be indicative thereof. Therefore, dental practitioners need to be aware of patients wishing to align their teeth and to provide them with the relevant information and, if appropriate, enable interdisciplinary treatment planning.

Head orthosis therapy in positional plagiocephaly: longitudinal 3D-investigation of long-term outcomes, compared with untreated infants and with a control group.

Background: As there are very few long-term studies on the effects of head orthosis on deformational plagiocephaly (DP), we investigated the outcomes of patients, including facial symmetry and dental occlusion. Methods: Forty-five infants with DP [cranial vault asymmetry index (CVAI) > 3.5 per cent] were divided into two groups: one treated with head orthosis (32 infants) and another without (13 infants). Another group without head asymmetry (CVAI ≤ 3.5 per cent) served as control. Using 3D-stereophotogrammetry, cranial asymmetry was analysed using symmetry-related variables [CVAI, posterior cranial asymmetry index (PCAI), and ear offset]. Data acquisition was performed before (T1) and at the end of treatment (T2), and at the age of 4 years (T3) for the treated group and at T1 and T3 for the remaining groups. Parameters of facial symmetry and dental occlusion were assessed at T3 for infants with DP. Results: Symmetry-related variables (∆T1-T3) improved significantly more in the treated than the control group, whereas these parameters did not differ significantly between the untreated and control group. Comparing the treated and untreated groups between T1 and T3, the reduction in the asymmetry at the treated group was significantly higher for the CVAI and PCAI. In follow-up, the untreated group showed higher incidences of facial asymmetries than the treated group. Seventy-five per cent of all lateral crossbites found in patients with DP were contralateral to the posterior flattening. Limitations: Due to ethical reasons, the investigation is a non-randomized study. Parameters of facial symmetry were only assed for the treated and untreated groups. Conclusion: Head orthosis therapy in patients with DP leads to significantly better long-term outcomes. Facial asymmetries are more frequent in patients with DP who do not receive this treatment.

TMJ pathomorphology in patients with JIA-radiographic parameters for early diagnosis.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is often accompanied by pathomorphological changes to the temporomandibular joint (TMJ). By analyzing orthodontical orthopantomograms of JIA patients the aims of the study were a) classification of condyle changes, b) quantification of bony asymmetries of condylar destruction and c) detection of relationships between disease duration and TMJ-involvement. PATIENTS/METHODS: 46 caucasian JIA-patients (28 female; 18 male; < 16.0 years) were enrolled, each joint (n = 92) was morphologically assessed by means of orthopantomogram, quantitatively analysed and compared with duration of general disease. Condyle morphology was assessed using the Billiau scale for severity of destruction [1]. The quantitative analysis was based on ratios of condyle, ramus and mandible height. RESULTS: Patients were divided into groups (Group I - slightly affected, n = 36; Billiau severity 0-2; condyle findings: X-ray normal, condyle erosions, condylar flattening; Group II - severely affected, N = 10; Billiau severity 3-4; condyle findings: condylar flattenings and erosions, unilateral/bilateral complete loss of condyles), based on morphological analysis of condylar destruction. Duration of disease was significantly longer in Group II (8.9 ± 5.2 years) than in Group I (4.6 ± 4.7 years). Asymmetries of condyle, ramus and mandible height, quantitatively analysed by contralateral comparison, were significantly more marked in patients of Group II than of Group I. CONCLUSIONS: Orthopantomogram imaging can be used in orthodontics clinical routine to detect TMJ-pathologies and is an important reference for monitoring progression of JIA. Classification into severe and slightly affected TMJ is possible by analysis of condylar pathomorphology. An association between degree of destruction, extent of lower jaw asymmetry and disease duration is suggested by the results.

Correlation between oral health-related quality of life and orthodontic treatment need in children and adolescents-a prospective interdisciplinary multicentre cohort study.

PURPOSE: Oral health-related quality of life (OHRQoL) is a construct for assessing the self-perceived oral health of patients. The aim of this study was to investigate the correlation between OHRQoL and orthodontic treatment need in consideration of demographic and psychological factors. PATIENTS AND METHODS: This multicentre study included 250 patients with an indication for orthodontic diagnostics. In cooperation with the Institute of Clinical Psychology at the University of Würzburg, validated and internationally acknowledged questionnaires were selected to assess OHRQoL (COHIP-G19) and health-related quality of life (HRQOL). Self-esteem and behavioural problems were taken into consideration as possible psychological factors. Orthodontic treatment need was assessed using the Index of Orthodontic Treatment Need-Dental Health Component (IOTN-DHC), the Index of Orthodontic Treatment Need-Aesthetic Component (IOTN-AC) and the Dental Aesthetic Index (DAI). Possible significant correlations between the collected parameters and OHRQoL were evaluated by means of linear regression analysis. RESULTS: Objective orthodontic treatment need (IOTN-DHC and DAI) was significantly correlated with OHRQoL. Further factors significantly influencing OHRQoL in children and adolescents were age, HRQOL, self-esteem and behavioural problems. CONCLUSIONS: Objective orthodontic treatment need significantly influences OHRQoL in children and adolescents. Further studies are required to investigate if OHRQoL may be improved by correcting misaligned teeth and jaws.

Wild-type isolates of Porphyromonas gingivalis derived from periodontitis patients display major variability in platelet activation.

In vitro studies revealed that Porphyromonas gingivalis (Pg), a pathogen intimately associated with the onset and progression of periodontitis, is able to activate platelets, thus linking periodontal inflammation with the endangerment of vascular health. As wild-type Pg strains are characterized by major genetic heterogeneity, the commonness of platelet-activating Pg strains in periodontitis patients is unknown as of yet. Therefore, this study evaluated the platelet activation capacity of wild-type Pg isolates sampled from patients with aggressive periodontitis. METHODS: Extent and velocity of platelet aggregation were determined by light transmission aggregometry. Platelet surface expression of P-selectin was measured by flow cytometry, activation of p38 MAP kinase, and protein kinase C by Western blot using phospho-specific antibodies. RESULTS: Pg isolates displayed high variability regarding extent and velocity of platelet activation, as well as the involved activating pathways. Corresponding results were observed for platelet P-selectin expression, activation of p38 MAP kinase, or protein kinase C. Inhibitors of platelet immune receptor FcγRIIA and protease-activated receptors revealed several, diverging pathways of activation. Some isolates induced platelet aggregation even in the presence of potent therapeutical platelet inhibitors. CONCLUSIONS: Chronic bacteremia involving specific, platelet-activating Pg strains may constitute a substantial hazard for the integrity of cardiovascular health.

Head Orthosis Therapy in Positional Plagiocephaly: Influence of Age and Severity of Asymmetry on Effect and Duration of Therapy.

BACKGROUND: Only a few studies investigating the optimal time point at which to start orthotic treatment for deformational plagiocephaly take into account the severity of skull asymmetry. The present study performs a three-dimensional analysis of the effects of age and severity of asymmetry on the final outcome. METHODS: A total of 144 patients with deformational plagiocephaly treated by molding orthosis were examined and divided into three age groups (group I, <24 weeks; group II, ≥24 to <32 weeks; and group III, ≥32 weeks) and two severity levels (mild to moderate, 30-degree cranial vault asymmetry ≥3 mm to ≤12 mm; and moderate to severe, 30-degree cranial vault asymmetry >12 mm). The extent of the reduction of asymmetry was analyzed using three-dimensional stereophotogrammetry. RESULTS: Therapy with molding orthosis led to a significant reduction in asymmetry in all defined age groups. Efficacy of reduction decreased with increasing age. Successful treatment (cranial vault asymmetry index <3.5 percent) was achieved in 83, 69, and 40 percent of patients with mild to moderate asymmetry in groups I, II, and III, respectively; and in 50, 30, and 7 percent of patients with moderate to severe asymmetry in groups I, II, and III, respectively. The average duration of treatment increased from 18.6 weeks to 25.3 weeks (age groups I and III). CONCLUSION: Age at the beginning of treatment and severity of asymmetry have a definite impact on the duration and effectiveness of molding orthosis therapy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

PTH1R Mutants Found in Patients with Primary Failure of Tooth Eruption Disrupt G-Protein Signaling.

AIM: Primary failure of tooth eruption (PFE) is causally linked to heterozygous mutations of the parathyroid hormone receptor (PTH1R) gene. The mutants described so far lead to exchange of amino acids or truncation of the protein that may result in structural changes of the expressed PTH1R. However, functional effects of these mutations have not been investigated yet. MATERIALS AND METHODS: In HEK293 cells, PTH1R wild type was co-transfected with selected PTH1R mutants identified in patients with PFE. The effects on activation of PTH-regulated intracellular signaling pathways were analyzed by ELISA and Western immunoblotting. Differential effects of wild type and mutated PTH1R on TRESK ion channel regulation were analyzed by electrophysiological recordings in Xenopus laevis oocytes. RESULTS: In HEK293 cells, activation of PTH1R wild type increases cAMP and in response activates cAMP-stimulated protein kinase as detected by phosphorylation of the vasodilator stimulated phosphoprotein (VASP). In contrast, the PTH1R mutants are functionally inactive and mutant PTH1R/Gly452Glu has a dominant negative effect on the signaling of PTH1R wild type. Confocal imaging revealed that wild type PTH1R is expressed on the cell surface, whereas PTH1R/Gly452Glu mutant is mostly retained inside the cell. Furthermore, in contrast to wild type PTH1R which substantially augmented K+ currents of TRESK channels, coupling of mutated PTH1R to TRESK channels was completely abolished. CONCLUSIONS: PTH1R mutations affect intracellular PTH-regulated signaling in vitro. In patients with primary failure of tooth eruption defective signaling of PTH1R mutations is suggested to occur in dento-alveolar cells and thus may lead to impaired tooth movement.

Combining wrist age and third molars in forensic age estimation: how to calculate the joint age estimate and its error rate in age diagnostics.

BACKGROUND: Forensic age estimation in living adolescents is based on several methods, e.g. the assessment of skeletal and dental maturation. Combination of several methods is mandatory, since age estimates from a single method are too imprecise due to biological variability. The correlation of the errors of the methods being combined must be known to calculate the precision of combined age estimates. AIM: To examine the correlation of the errors of the hand and the third molar method and to demonstrate how to calculate the combined age estimate. SUBJECTS AND METHODS: Clinical routine radiographs of the hand and dental panoramic images of 383 patients (aged 7.8-19.1 years, 56% female) were assessed. RESULTS: Lack of correlation (r = -0.024, 95% CI = -0.124 to + 0.076, p = 0.64) allows calculating the combined age estimate as the weighted average of the estimates from hand bones and third molars. Combination improved the standard deviations of errors (hand = 0.97, teeth = 1.35 years) to 0.79 years. CONCLUSION: Uncorrelated errors of the age estimates obtained from both methods allow straightforward determination of the common estimate and its variance. This is also possible when reference data for the hand and the third molar method are established independently from each other, using different samples.

Spectrum of positional deformities - is there a real difference between plagiocephaly and brachycephaly?

AIM: This study analyses pathomorphological and physiological head shapes and classifies the pathomorphology in positional plagiocephaly and brachycephaly. PATIENTS AND METHODS: 78 infants with a positional plagiocephaly (5.99 months) and 32 infants with a positional brachycephaly (6.53 months) with a Cephalic index > 94% were investigated in this study and compared to a matched control group of 35 infants. The head shapes were analysed by stereophotogrammetry 3D data. RESULTS: The cephalic index, the total width, and coronal circumference were the highest values in patients with brachycephaly and the lowest values in the control group. The asymmetry of the head showed that the diagonal difference in brachycephalic patients more than doubled, and in patients with plagiocephaly almost tripled compared to the controls. A significantly higher total volume and vertex height was found for the patients with plagiocephaly and the patients with brachycephaly compared to the controls. CONCLUSION: The cephalic index is a valuable and reliable parameter in order to differentiate positional deformities from unaffected skulls. Pathomorphology of a plagiocephaly is associated with the most severe asymmetry of the head. Plagiocephaly and brachycephaly overlap in several criteria. Therefore it seems justified to speak of a continuum rather than to differentiate between plagiocephaly and brachycephaly.

Expanding the spectrum of PTH1R mutations in patients with primary failure of tooth eruption.

OBJECTIVES: Primary failure of tooth eruption (PFE) is a rare autosomal-dominant disease characterized by severe lateral open bite as a consequence of incomplete eruption of posterior teeth. Heterozygous mutations in the parathyroid hormone 1 receptor (PTH1R) gene have been shown to cause PFE likely due to protein haploinsufficiency. To further expand on the mutational spectrum of PFE-associated mutations, we report here on the sequencing results of the PTH1R gene in 70 index PFE cases. MATERIALS AND METHODS: Sanger sequencing of the PTH1R coding exons and their immediate flanking intronic sequences was performed with DNA samples from 70 index PFE cases. RESULTS: We identified a total of 30 unique variants, of which 12 were classified as pathogenic based on their deleterious consequences on PTH1R protein while 16 changes were characterized as unclassified variants with as yet unknown effects on disease pathology. The remaining two variants represent common polymorphisms. CONCLUSIONS: Our data significantly increase the number of presently known unique PFE-causing PTH1R mutations and provide a series of variants with unclear pathogenicity which will require further in vitro assaying to determine their effects on protein structure and function. CLINICAL RELEVANCE: Management of PTH1R-associated PFE is problematic, in particular when teeth are exposed to orthodontic force. Therefore, upon clinical suspicion of PFE, molecular DNA testing is indicated to support decision making for further treatment options.

[Primary failure of eruption (PFE). Clinical and molecular genetics analysis]. / Défaut primaire d'éruption (DPE). Analyse génétique clinique et moléculaire∗

BACKGROUND: The term "primary failure of eruption" (PFE) refers to the complete or partial failure of a primary non-ankylosed tooth to erupt due to a disturbance of the eruption mechanism. Up to now, the molecular basis for this failure was unknown. PATIENTS AND METHODS: Four families were studied in whom at least two members were affected by non-syndromic PFE as part of a clinical and molecular genetics study. Radiological diagnostics (OPTs) were carried out in all patients and their unaffected relatives (control group). The genetic analysis included a genomewide linkage analysis followed by direct DNA sequencing of positional candidate genes. RESULTS: Starting from the index patients, we were able to reconstruct pedigrees over two and/or three generations in the families that indicated an autosomal-dominant mode of inheritance of non-syndromic PFE. Fifteen patients were diagnosed with PFE. Gender distribution was nearly equal (7 female, 8 male). Molecular genetic analysis of the PTHR1 gene revealed three distinct heterozygous mutations (c.1050-3C>G; c.543 + 1G>A; c.463G>T). Unaffected persons exhibited no mutations. CONCLUSION: Knowledge of the genetic causes of non-syndromic PFE can now be used for the differential diagnosis of eruption failure. It permits affected family members to be identified early and may lead to new treatment possibilities in the long term. The genetically-verified diagnosis of "primary failure of eruption" can protect patients and orthodontists from years of futile treatment, because orthodontic treatment alone does not lead to success. Moreover, it has a negative influence on unaffected teeth and areas of the jaw.

Short-term pharyngeal airway changes after mandibular advancement surgery in adult Class II-Patients--a three-dimensional retrospective study.

The purpose of this study was to investigate volume changes in posterior airway space (PAS) after bilateral mandibular advancement surgery. Measurements were taken based on three-dimensional (3D) records available for a large and homogeneous cohort of patients. Pre- and postoperative CBCT scans of 102 adult patients with Class II dysgnathia were visualized and analyzed using 3D software (Mimics® Innovation Suite 14.1; Materialise, Leuven, Belgium). The PAS was divided into three segments by three planes parallel and one plane perpendicular to the Frankfort horizontal plane. Total volume, partial volumes, and cross-sectional areas were calculated from the pre- and postoperative scans. Dahlberg coefficients were obtained to verify each parameter for the measurements' reliability. The statistical significance of the changes observed was analyzed by Wilcoxon's rank-sum test. Highly significant (p=0.000) increases in total posterior airway volume (+32.0%) were noted as an effect of mandibular advancement surgery, amounting to 45.6% in the lower PAS third compared to 38.8% in the middle and 12.5% in the upper PAS third. We also obtained highly significant (p=0.000) increases in all the cross-sectional areas investigated, amounting to 48.5% on the soft-palate level compared to 21.6% on the level of the epiglottis tip, and 14.6% on the hard-palate level. These results demonstrate that bilateral mandibular advancement surgery in Class II-Patients leads to significant increases in PAS volume and significant widening of the narrower sites inside the pharynx.

Three-dimensional analysis of positional plagiocephaly before and after molding helmet therapy in comparison to normal head growth.

OBJECTIVE: Stereophotogrammetry enables a simple and radiation free longitudinal analysis of skull asymmetries: in a three-dimensional coordinate system various distances (length, breadth, cephalic index, oblique diameters, ear shift, head circumference) can be analyzed. We also defined separate volume sections in order to further quantify the degree of asymmetry in the posterior and anterior components of both sides of the head. PATIENTS AND METHODS: In 51 infants (mean age, 6 months; SD 0.97) with positional plagiocephaly, we determined these parameters at the beginning as well as at the end of molding helmet therapy (mean therapy time 4.9 months). Thirty-seven infants without positional deformity (mean age, 6.4 months; SD 0.3) served as control group and provided data about what appears to be normal and how these parameters change during growth over a comparable period of time. RESULTS: Compared with the control group, the plagiocephalic heads were more brachycephalic, but closely approximated the normal shape under molding therapy. The striking volume difference between the left and right posterior sections in the plagiocephalic children (the mean volume of the flattened side being 21% smaller than the one on the contralateral side) improved as well (to a residual difference of mean 8%) and ended up with a value close to the control group (mean 6%). CONCLUSION: There is a broad clinical application area for stereophotogrammetry analyzing skull morphology: In plagiocephalic infants we demonstrate impressive changes of head shape under molding therapy; in normal-looking infants we describe the extent of unperceived asymmetry.