Multivariate GWAS of Structural Dental Anomalies and Dental Caries in a Multi-Ethnic Cohort

Odontogenesis is a complex process, where disruption can result in dental anomalies and/or increase the risk of developing dental caries. Based on previous studies, certain dental anomalies tend to co-occur in patients, suggesting that these traits may share common genetic and etiological components. The main goal of this study was to implement a multivariate genome wide association study approach to identify genetic variants shared between correlated structural dental anomalies and dental caries. Our cohort (N = 3,579) was derived from the Pittsburgh Orofacial Clefts Study, where multiple dental traits were assessed in both the unaffected relatives of orofacial cleft (OFC) cases (n = 2,187) and unaffected controls (n = 1,392). We identified four multivariate patterns of correlated traits in this data: tooth agenesis, impaction, and rotation (AIR); enamel hypoplasia, displacement, and rotation (HDR); displacement, rotation, and mamelon (DRM); and dental caries, tooth agenesis and enamel hypoplasia (CAH). We analyzed each of these four models using genome-wide multivariate tests of association. No genome-wide statistically significant results were found, but we identified multiple suggestive association signals (P ≤ 10−5) near genes with known biological roles during tooth development, including ADAMTS9 and PRICKLE2 associated with AIR; GLIS3, WDR72, and ROR2 associated with HDR and DRM; ROBO2 associated with DRM; BMP7 associated with HDR; and ROBO1, SMAD2, and MSX2 associated with CAH. This is the first study to investigative genetic associations for multivariate patterns of correlated dental anomalies and dental caries. Further studies are needed to replicate these results in independent cohorts.

The effectiveness of orthodontic and osteopathic correction in patients with dental anomalies and musculoskeletal dysfunction of the temporomandibular joint in the presence of concomitant somatic dysfunctions and without it

Introduction. The influence of the dental apparatus on the balance of the body in an upright position has been widely discussed in the literature for several decades. Examination of the patient taking into account his postural balance makes it possible to clarify the reasons for the low effectiveness of pain syndromes treatment of the craniocervical region caused by malocclusion, as well as ineffective correction of musculoskeletal dysfunction of the temporomandibular joint (MSD TMJ) associated with posture disorders.The aim of the study is to evaluate the effectiveness of treatment of patients with dental anomalies and musculoskeletal dysfunctions of the temporomandibular joint and concomitant somatic dysfunctions (if any) by methods of orthodontic and osteopathic correction.Materials and methods. The study involved 102 patients aged from 18 to 45 years with TMJ. All patients underwent orthodontic and osteopathic examination. 3 groups of patients were formed: № 1 — exclusively with dental anomalies TMJ (occlusive dysfunction), who received only orthodontic treatment, № 2 with concomitant somatic (extra-occlusive) dysfunctions, who received only orthodontic treatment, and №3 with concomitant somatic (extra-occlusive) dysfunctions, who received both orthodontic and osteopathic treatment. Orthodontic treatment of musculoskeletal dysfunction of the TMJ consisted of the occlusive kappa manufacturing. Osteopathic correction was carried out individually, taking into account the identified somatic dysfunctions, on average 3 sessions. Patients also received drug therapy, and they performed myohymnastics for the masticatory muscles. The clinical dysfunction index (Helkimo M.) was used to control the elimination dynamics of the TMJ's musculoskeletal dysfunction symptoms. The assessment of the pain dynamics in the TMJ was carried out by a visual-analog scale (VAS). The evaluation of the osteopathic treatment effectiveness was carried out on the basis of computer stabilometry data and osteopathic examination data. A stabilometric study was performed on the «ST-150» («Biomera») stabiloplatform in the Romberg sample (European foot installation) with open and closed eyes in two positions of the lower jaw: 1) in a state of physiological rest (tooth rows are separated); 2) in the kappa with closed tooth rows.Results. The MSD TMJ symptoms were eliminated 10 weeks after the start of treatment in all (100 %) patients of group № 1 and group № 3. Among the patients in group № 2, only 12,1 % of patients had complete absence of MSD TMJ symptoms, while all patients in this group had a statistically significant decrease in the clinical index of Helkimo dysfunction. In one third of the group № 2 patients on the 12th week of orthodontic treatment, headaches and/or pains in other parts of the musculoskeletal system (neck, back, shoulders, arms) prevailed among complaints and which were previously indicated in the anamnesis. This occurred after the elimination of the MSD TMJ symptoms. The absolute majority of patients in group № 3 (97,1 %) noted the complete disappearance of headaches and/or pains in other parts of the musculoskeletal system (neck, back, shoulders, arms). Also, in patients of this group, stabilometric indicators were normalized in a state of physiological rest and in the kappa.Conclusion. Patients with somatic dysfunctions need complex treatment with the participation of an osteopath and a dentist. When assessing the osteopathic status of a patient, it is important to determine whether the patient has only occlusive dysfunctions or there are also extra-occlusive ones. Additional osteopathic correction is recommended for patients with extraocclusive dysfunctions in order to achieve treatment results comparable in effectiveness and timing.

The prevalence and management of patients with hypodontia: A cross -sectional study

Background: Hypodontia is one of the most common anomalies in dentistry. Hypodontia has a negative impact on oral health-related quality of life with patients best seen in a multidisciplinary clinic to improve treatment outcomes. Aim: To investigate the prevalence of hypodontia and its association with other dental anomalies, as well as malocclusion, and to investigate the treatment planned for patients attending the clinic and whether the type of missing teeth affected the proposed treatment. Materials and Methods: Analysis of consecutive patients attending the hypodontia clinic at a dental hospital between February and November 2020. A total of 100 patients who met the inclusion criteria were identified. Data collected included the following: age/sex; number and type of missing teeth; pre-treatment occlusion; presence of other dental anomalies; and planned treatment. Results: A total of 100 patients (55% female; age range = 7–41 years; mean age = 18 years) were included. Of the cohort, 47% had a class I skeletal relationship and participants were significantly less likely to have a class III skeletal or incisor relationship; 45% had another dental anomaly with the most common being microdontia. Space opening was the preferred treatment option for those managed by orthodontic treatment with resin-bonded bridges most likely to be used for restoration of spaces, 86%. Conclusion: Lower second premolars were the most commonly missing teeth. Participants were significantly less likely to have a class III incisor or skeletal relationship than class I or II. Space opening was the favoured approach for orthodontic treatment, particularly for maxillary lateral incisors.

METHOD OF HEALTHY TEETH EXTRACTION IN ORTHODONTIC TREATMENT

In the treatment of orthodontic patients, the most difficult and controversial is the question of removing healthy teeth. The aim was to evaluate the 30-year orthodontic clinical experience of the staff of the Postgraduate Education Department of Orthodontists for the use of medical methods of removal of individual healthy teeth in the treatment of dental anomalies. The aim of our study is to evaluate 30 years of orthodontic clinical practice of the staff of the Postgradu- ate Education Department of Orthodontists for the use of medical removal of individual healthy teeth in the treatment of dental anomalies. 1340 dental outpatient cards of orthodontic patients who underwent orthodontic treatment and completed it with a positive result were reviewed at two clinical bases of the Postgraduate Education Department of Orthodontists. The analysis of selected outpatient cards was performed taking into account the age and sex of patients, as well as depending on the type of pathological occlusion (according to Angle) and the type of teeth removed. Cards of patients with Angle's class I and II pathology were selected for scientific analysis. 241 patient underwent tooth extraction at both bases in total in terms of treatment, which is 17.99%. The number of patients with removed temporary teeth was 59.39% (143/241), patients with removed permanent teeth - 40.7% (98/241). Permanent teeth were removed 1.45 times more often at the clinic "Orthodontist", which is explained by the higher frequency of requests for orthodontic care from adults and adolescents. On the basis of the Postgraduate Education Department of Orthodontists, patients with deciduous teeth predominate - 69% (51/74) against 45% (75/167) in the clinic "Orthodontist". This is due to the fact that the main contingent of patients who seek help from the department are patients in the age of variable occlusion, which means that the Hotz method and the author's method of corrective removal of temporary molars are used more often. A detailed analysis of the documentation of patients was performed at the base of the Postgraduate Edu- cation Department of Orthodontists who were treated with the use of individual teeth extraction by periods of occlusion. Children in the period of the first half of the variable occlusion accounted for 39.19% (29/74), chil- dren in the second half of the variable occlusion - 25.67% (19/74), and patients older than 13 years - 35.14% (26/74). In female patients, regardless of age, tooth extraction is performed 13% -15% of cases more often than in men, which is due to a more attentive attitude to the appearance of girls by their parents. Among patients with various types of pathological occlusions treated with the method of removal of individual healthy teeth, children, adolescents and adults with Angle class I occlusion pathology accounted for 53.94% (130/241). Assessing the frequency of application of the method of extraction of healthy teeth by age, we can say that in pathology of class II according to Angle most often the method is used in patients with permanent occlusion in 38.73% (43/111). In the treatment of pathology of class I according to Angle, the removal of healthy teeth is twice as often performed in alternating occlusion than in permanent. In the treatment of pathology of class II according to Angle, the method of removing individual teeth is more often used in patients with permanent occlusion. Research on the consequences of removing individual healthy teeth in orthodontic treatment is relevant and timely. Both in the private sector of orthodontic care and on the clinical basis of the Postgraduate Education Department of Orthodontists, about a fifth of patients of any age and any orthodontic pathology are treated orthodontically using the clinical method of removing individual healthy teeth.

THE ANALYSIS OF THE PREVALENCE OF DENTAL ANOMALIES IN UZHHOROD SCHOOLCHILDREN

The health of the oral cavity is an important component of the overall physical, mental and social well- being of each person. It is known that untimely detection and treatment of patients with dentoalveolar anomalies can lead not only to social maladaptation of this category of people but also to an increase in the risk of developing a carious process, periodontal diseases, as well as dysfunction of the temporomandibular joint. The presence of a dentoalveolar anomaly in a child can lead to a social disadvantage of patients among peers, as well as loss of active career growth in young and mature age. The incidence rate may vary considerably depending not only on the country of research but also on its region, as well as sex and age of the studied categories of people. The patients' parents specify the type and duration of feeding, the presence of such bad habits as sucking fingers, lips, or the tongue, respiratory features (sleeping with an open mouth), whether a child was followed up by otolaryngologist or neurologist for adenoids, sinusitis, rhinitis, as well as other diseases that can negatively affect the development of the patient's chewing apparatus. In an objective examination, attention was paid to the disturbance of nasal breathing, visually evaluated the amplitude and TMJ movement range. With an increase in age in the examined children there was a de- crease in the prevalence of deep bite, while the frequency of detecting mesial, open bite, as well as the dis- placement of dental arches from the middle line, increased. Rotated teeth, as well as disturbance of interdental gaps was detected more frequently with age while diastems were detected less frequently. The sharp decrease in the frequency of dental anomalies is observed in the transition from the II period of a variable bite (11-13 years) to the period of a constant bite (14-17 years). The study showed that regular check-ups are the most effective methods for identifying patients with tooth anomalies in schoolchildren and can significantly reduce the number of patients who need this type of treatment with an adequate orthodontic care management. The purpose of the study is to analyze the prevalence of dentoalveolar anomalies in schoolchildren of Uzhgorod. Material and methods. The study involved 339 schoolchildren in Uzhgorod. An analysis of the prevalence of dentoalveolar anomalies was carried out in three age groups: the first period of the mixed bite (6–9 years), the second period of the mixed bite (10–13 years), and the permanent bite (14–17 years). Results. It has been shown that dentoalveolar anomalies occur in the majority (78.6%) of school-age children. The most common anomalies of the teeth position (47.1%) and anomalies are the ratios of dental arches (37.3%). Anomalies in the size of the jaws (11.5%) and dentoalveolar anomalies of functional origin (4.1%) occur less often. However, 70.4% of all dentoalveolar anomalies are combined. Dentofacial anomalies were observed in children aged 10 to 13 years (II period of a shifting bite) more often. A sharp decrease in the frequency of dentoalveolar anomalies is observed during the transition from the II period of a mixed bite (11-13 years) to the I period (14-17 years) of a permanent bite. Conclusion. The study showed that medical examinations and preventive examinations are the most effective methods for identifying patients with dentoalveolar anomalies in schoolchildren and, with the adequate orthodontic care management, can significantly reduce the number of patients requiring this type of treatment.

Dental Anomaly Detection Using Intraoral Photos Via Deep Learning

Children with orofacial clefting (OFC) present with a wide range of dental anomalies. Identifying these anomalies is vital to understand their etiology and to discern the complex phenotypic spectrum of OFC. Such anomalies are currently identified using intra-oral exams by dentists, a costly and time-consuming process. We claim that automating the process of anomaly detection using deep neural networks (DNNs) could increase efficiency and provide reliable anomaly detection while potentially increasing the speed of research discovery. This study characterizes the use of` DNNs to identify dental anomalies by training a DNN model using intraoral photographs from the largest international cohort to date of children with nonsyndromic OFC and controls (OFC1). In this project, the intraoral images were submitted to a Convolutional Neural Network (CNN) model to perform multi-label multi-class classification of 10 dental anomalies. The network predicts whether an individual exhibits any of the 10 anomalies and is able to do so significantly faster than a human rater. For every anomaly except mammalons, F1 scores suggest that our model performs competitively at anomaly detection when compared to a dentist with 8 years of clinical experience. In addition, we use saliency maps to provide a post-hoc interpretation for our model’s predictions. This enables dentists to examine and verify our model’s predictions.

Fine Breakpoint Mapping by Genome Sequencing Reveals the First Large X Inversion Disrupting the NHS Gene in a Patient with Syndromic Cataracts

Inversions are structural variants that are generally balanced. However, they could lead to gene disruptions or have positional effects leading to diseases. Mutations in the NHS gene cause Nance-Horan syndrome, an X-linked disorder characterised by congenital cataracts and dental anomalies. Here, we aimed to characterise a balanced pericentric inversion X(p22q27), maternally inherited, in a child with syndromic bilateral cataracts by breakpoint mapping using whole-genome sequencing (WGS). 30× Illumina paired-end WGS was performed in the proband, and breakpoints were confirmed by Sanger sequencing. EdU assays and FISH analysis were used to assess skewed X-inactivation patterns. RNA expression of involved genes in the breakpoint boundaries was evaluated by droplet-digital PCR. We defined the breakpoint position of the inversion at Xp22.13, with a 15 bp deletion, disrupting the unusually large intron 1 of the canonical NHS isoform, and also perturbing topologically-associated domains (TADs). Moreover, a microhomology region of 5 bp was found on both sides. RNA analysis confirmed null and reduced NHS expression in the proband and his unaffected mother, respectively. In conclusion, we report the first chromosomal inversion disrupting NHS, fine-mapped by WGS. Our data expand the clinical spectrum and the pathogenic mechanisms underlying the NHS defects.