Orthodontic Treatment of a Patient With Non-Syndromic Oligodontia and a Skeletal Class â ¢ Relationship: A Case Report and Six Years' Follow-Up.

Partial edentulism, characterized by the congenital absence of six or more permanent teeth (oligodontia), excluding the third molars, manifests with variable maxillofacial skeletal morphologies and occlusions, depending on the site and number of missing teeth, complicating treatment planning for occlusion and gain of function. Herein, we describe the case of a patient with seven non-syndromic congenitally missing permanent teeth (four in the maxillary and three in the mandibular dentition, excluding the third molars), who underwent orthodontic treatment, restorative procedures, and long-term follow-up for six years. The patient was an 18-year-old man presenting with a chief complaint of congenital absence of some permanent teeth and dental malalignment on the first visit. The mandibular right central incisor, bilateral mandibular second premolars, bilateral maxillary lateral incisors, and bilateral maxillary canines were congenitally absent, while the deciduous maxillary lateral incisors, maxillary canines, and mandibular second molars were over-retained bilaterally. Since the persisting deciduous teeth were remarkably well preserved, the patient was willing to retain them as far as possible; thus, we chose orthodontic and restorative treatment to preserve the deciduous teeth. Occlusion was established after the initiation of dynamic orthodontic treatment; restorative treatment with resin-based materials was performed for the bilateral maxillary deciduous incisors, bilateral maxillary deciduous canines, and bilateral mandibular second primary molars after bracket removal, and the retention phase of orthodontic treatment was initiated. At present, six years after establishing retention, the patient exhibits a good occlusal relationship. It is difficult to achieve complete space closure using orthodontic treatment alone in cases with six or more congenitally missing permanent teeth. In addition to considerations for age, esthetic issues due to missing permanent teeth, and maxillofacial skeletal morphology, it is necessary to preserve the deciduous teeth as much as possible and ensure multidisciplinary medical cooperation, including the transition to prosthodontic treatment during long-term follow-up.

Patterns of tooth agenesis in individuals with Down syndrome: A secondary analysis using the Tooth Agenesis Code.

AIMS: Tooth agenesis (TA) is common in Down syndrome (DS). It is unknown whether this agenesis occurs in specific patterns, which is important regarding treatment planning and aetiological research. This study aimed to aggregate and analyze patterns of TA, excluding third molars, in individuals with DS using the tooth agenesis code (TAC). METHODS AND RESULTS: The study was designed as a secondary analysis, following STROSA guidelines. The search (MEDLINE-PubMed) and selection process resulted in six included studies encompassing 241 individuals with DS. TA data were systematically converted into TACs and analyzed per dentition, per jaw, and per tooth type. Symmetry was evaluated. The prediction was calculated for oligodontia. In the 155 cases with TA 86 distinct Overall-TAC patterns were identified. The most common patterns were bilateral maxillary lateral incisor agenesis (TAC002.002.000.000;10.3%), bilateral mandibular second premolar agenesis (TAC000.000.016.016;5.8%), and unilateral left maxillary lateral incisor agenesis (TAC000.002.000.000;5.2%). Symmetry in TA patterns was observed in 49.6% of TA cases in the maxilla and 52.3% in the mandible. The simultaneous absence of both mandibular central incisors had a large predictive value for oligodontia (OR12.44;95% CI:4.97-31.84; p < .001). CONCLUSION: Predominant TA patterns exist in DS. Observation of mandibular central incisor agenesis can promote early diagnosis of oligodontia in DS.

Enamel hypoplasia with nonsyndromic oligodontia: A rare case report.

Enamel hypoplasia is an exclusive ectodermal disturbance, related to alterations in the organic enamel matrix which can cause white flecks, narrow horizontal bands, lines of pits, grooves, and discoloration of the teeth. It can result in compromised oral health that causes physiological and psychological disturbances. Management of enamel hypoplasia not only includes esthetic and functional rehabilitation of the patient but also requires a positive rapport building with the patient due to psychosocial issues. The present case reports elucidate step-by-step management of 16-year-old female patient who presented with localized enamel hypoplasia with severely decayed anterior teeth, poor dental esthetics, and oligodontia of the lower teeth.

Non-syndromic tooth agenesis in Latvian adolescent dental patients: a retrospective study with relevant literature review.

AIM: To investigate the prevalence of tooth agenesis and associated dental anomalies in Latvian adolescent dental patients and compare it to other European countries. DESIGN: Cross-sectional study of 2692 11-to-14-year-old patients (39.9% males and 60.1% females) attending Riga Stradins University Institute of Stomatology with panoramic radiographs taken between August 2020 and September 2021. Patients with any genetic syndromes were excluded. Data on tooth agenesis (excluding third molars) and other dental anomalies were recorded. RESULTS: The prevalence of tooth agenesis in Latvian adolescent dental patients was 9.3% with no statistically significant difference between genders (χ2 test, p = 0.472). The most commonly missing teeth were mandibular second premolars, followed by upper lateral incisors and upper second premolars. There was a statistically significant association with the presence of other dental anomalies in tooth agenesis patients (p < 0.001). CONCLUSIONS: This study found that the prevalence of non-syndromic tooth agenesis in Latvian adolescent dental patients was 9.3% with no statistically significant differences between the genders. Patients with tooth agenesis have a statistically significant possibility of the presence of other dental anomalies (p < 0.001).

Hair Evaluation in Orthodontic Patients with Oligodontia.

Oligodontia can be isolated or syndromic, associated with other ectodermal abnormalities. The aim of the study was to perform hair examination in orthodontic patients diagnosed with oligodontia with a low clinical expression of symptoms of ectodermal origin. All available orthodontic patients diagnosed with oligodontia in the permanent dentition were enrolled. Hair examination included clinical evaluation of the patients' hair, trichoscopy, trichogram and evaluation of the hair shafts under a polarized light microscope. In total, 25 patients, 18 males and 7 females, aged 6 to 24 years were evaluated for the presence of dental and hair abnormalities. The number of congenitally absent teeth ranged from 6 to 24 teeth and diastemas, microdontia, taurodontism and altered tooth shape were found in 23 patients. Hair disorders were found in 68% of the subjects. Hypotrichosis, the heterogeneity of shaft color and loss of pigment, androgenetic alopecia, telogen effluvium, trichoschisis, pili canaliculi, trichorrhexis nodosa and pseudomoniletrix were observed. Trichoscopy and trichogram are valid non-invasive diagnostic tests which could be used to differentiate between isolated and syndromic oligodontia in patients with a low clinical expression of ectodermal symptoms.

Orodental malformations associated with human MSX1 sequence variants.

BACKGROUND: MSX1 sequence variants have been known to cause human tooth agenesis (TA) with or without orofacial clefts. However, their roles during the whole processes of tooth development are not fully understood. This study aimed to characterize a 4-membered family with TA carrying a novel MSX1 pathogenic variant and investigate the disease mechanism. METHODS: The authors conducted whole exome analysis to define the disease-causing sequence variant. They performed microcomputed tomography, morphometric analyses, transcriptome profiling, and molecular characterization to study the affected teeth and the gene variant. RESULTS: The authors identified an MSX1 pathogenic variant, p.Glu232∗, in affected family members with TA and concomitant orodental anomalies, namely, prominent maxillary labial frenum, central incisor diastema, median maxillary anterior alveolar cleft, tooth fusion, mandibular molar dysmorphology, thin dentin layer, and slender dental roots. MSX1-defective teeth were not apparently microdontic but had thin dentin layers. The mandibular molars showed a homeotic transformation to maxillary counterparts. Genes involved in extracellular matrix organization and dentinogenesis, such as DMP1 and MMP20, were downregulated in dental pulp tissues of MSX1-defective teeth. The p.Glu232∗-truncated MSX1 properly localized to the nucleus but partially lost its transactivation ability. Analyzing reported cases indicated that truncation sequence variants within the homeobox domain of MSX1 caused a more severe TA phenotype than those outside of the homeobox domain, probably due to dominant negativity compared with haploinsufficiency. CONCLUSIONS: This study provides in vivo evidence that MSX1 contributes to developmental processes of various orodental tissues in humans. PRACTICAL IMPLICATIONS: Clinically, hypertrophic labial frenum, incisor diastema, and median maxillary anterior alveolar cleft might be considered diagnostic for MSX1-associated TA.

Bimaxillary fixed implant-supported zirconium oxide prosthesis therapy of an adolescent patient with non-syndromic oligodontia and two WNT10 variants: a case report.

Introduction and importance: Oligodontia is a rare genetic condition characterized by more than six congenitally missing teeth, either as an isolated non-syndromic condition or in association with other genetic syndromes. The impact of WNT10A variants on dental development increases with the presence of the c.321C>A variant and the number of missing teeth. Case presentation: A 21-year-old man with non-syndromic oligodontia was diagnosed at 15 years of age with misaligned teeth, speech problems, and the absence of 24 permanent teeth. Interdisciplinary collaboration between specialists was initiated to enable comprehensive treatment. DNA analysis confirmed that the patient was a carrier of the known pathogenic WNT10A variant c321C>A and WNT10A variant c.113G>T of unknown clinical significance. Clinical discussion: Dental implants are a common treatment; however, bone development challenges in adolescent patients with non-syndromic oligodontia necessitate careful planning to ensure implant success. Many WNT variants play crucial roles in tooth development and are directly involved in non-syndromic oligodontia, especially the WNT10 variant c.321C>A. Conclusion: A full-arch implant-supported monolithic zirconia screw-retained fixed prosthesis is a viable treatment option for young adults with non-syndromic oligodontia. Further studies are needed to clarify the possible amplifying effect of the WNT10A variants c321C>A and c.113G>T on the pathogenic phenotype of non-syndromic oligodontia.

Personalized and Complex Esthetic Oral Rehabilitation in a Case of Non-Syndromic Oligodontia.

Dental agenesis is one of the most common developmental anomalies in humans and it is frequently associated with several other oral abnormalities. The present case describes non-familial agenesis of permanent teeth in a twenty-one-year-old boy with no apparent systemic abnormalities. The treatment included a personalized and interdisciplinary approach involving endodontics, orthodontics, implant-supported restorations and prosthetic treatments. The treatment plan was thoroughly elaborated using photographic analysis, study models, orthopantomogram, CBCT and cephalograms. Virtual smile design, diagnostic waxing and mock-ups previsualized the treatment objectives. The edentulous spaces were reconstructed by inserting dental implants and monolithic zirconia implant-supported restorations. The final results showed a highly esthetic and functional rehabilitation. Periodic check-ups have shown that the stability of the result is well maintained and that the implant-supported restorations are an optimal solution for patients with multiple anodontia.

A 10-year-old boy with class II oligodontia treated with buccal fixed appliances and agenesis space closure of the four second premolars: Case report No. 230075 - Titularisation Collège Européen Orthodontie (CEO), European College of Orthodontics.

The patient presented in this case report is a 10-year-old boy with hyperdivergent skeletal Class II associated with familial genetic agenesis of the second premolars. The treatment plan chosen was to close the spaces of agenesis using a bimaxillary appliance fixed buccally. The advantages and disadvantages of this treatment option were discussed. The result was stable and made it possible to avoid an implant-prosthetic solution, which would undoubtedly have been more restrictive over time.

Clinical analysis of nonsyndromic oligodontia phenotypes.

OBJECTIVES: To provide references, this study investigated the clinical characteristics of patients with nonsyndromic oligodontia. METHODS: The information of 178 patients with oligodontia was collected, including histories, oral examinations, and panoramic radiographs. Tooth agenesis characteristics were calculated and evaluated. All the data were statistically analyzed with SPSS 24.0 software. RESULTS: No significant difference in the number of missing teeth was found between sexes nor between the right and left sides, and congenitally missing teeth affected the maxillary arch (P<0.05). The highest prevalence of tooth agenesis was observed in the mandibular second premolars. In the maxillary arch, the most common pattern of tooth agenesis was agenesis of the bilateral first and second premolars. The agenesis of the bilateral second premolars was observed in the mandibular arch. The prevalence of a symmetric pattern between the right and left quadrants was significantly higher than that of matched patterns between the maxillary and mandibular antagonistic quadrants. Approximately 16.85% of patients with nonsyndromic oligodontia were affected by other tooth-related anomalies. CONCLUSIONS: The common patterns of tooth agenesis were successfully identified in patients with nonsyndromic oligodontia. Dentists need to provide multidisciplinary treatments for patients with nonsyndromic oligodontia because of variations in occluding and full-mouth tooth agenesis patterns.

Tooth agenesis related to a novel KDF1 variant: A case report and literature review.

OBJECTIVES: To investigate the role of Keratinocyte Differentiation Factor 1 (KDF1) in ectodermal dysplasia (ED) and nonsyndromic tooth agenesis (NSTA) and perform a literature review. METHODS: Genome sequencing was used to identify genetic variants in a Thai, NSTA proband and validated through Sanger sequencing. Pathogenicity was assessed using ACMG guidelines, MetaRNN and AlphaMissense. A comprehensive review of KDF1/NSTA cases informed genotype-phenotype analysis of the proband. RESULTS: The proband revealed multiple missing teeth, caries and extensive periodontal disease. Deep phenotyping showed no signs of ED beyond tooth agenesis. The identified novel KDF1 variant, p.Ile243Leu, was classified as 'likely pathogenic' by ACMG and predicted as 'detrimental' by MetaRNN and AlphaMissense analyses. A total of 14 reviewed KDF1 cases revealed ED-associated variants (3 variants in 8 patients) clustering in the region of amino acids 251-275, within the DUF4656 domain, while NSTA-causing variants (4 variants in 6 patients) were typically found in amino- or carboxy-termini to this region. KDF1/NSTA cases exhibited an average of 15 missing teeth, with a higher prevalence in the mandible. CONCLUSION: This study identifies a novel KDF1 variant-related NSTA in Thai people. The genotype-phenotype correlates suggest a distinctive pattern and tooth agenesis of KDF1-related NSTA.

Difficulties experienced by dentists and orthodontists regarding ethical issues when announcing the diagnosis of a rare oral disease: a qualitative study in Marseille, France.

PURPOSE: It is traditionally considered that breaking bad news to patients does not represent a cause for concern for dental professionals. However, there are situations where they will be confronted with this task, as in the case of rare dental diseases. Little information is available regarding the feelings of healthcare professionals on this subject. There are no qualitative studies that explore how a diagnosis of oligodontia is announced to patients by dentists and orthodontists. The aim of our study is to explore the difficulties and ethical issues experienced by dental health professionals when they have to announce a diagnosis of oligodontia to a patient and their family. METHODS: This study relied on a qualitative research method using focus groups of dentists and orthodontists and a thematic analysis procedure. RESULTS: The difficulties experienced could be summarised within five topics: organisational difficulties, difficulties with the management of dental treatment and with the administrative management associated with this anomaly, difficulties with the content of the announcement, and relational difficulties. These could be grouped in two categories: practical difficulties and ethical difficulties. CONCLUSION: This survey allowed us to understand the difficulties encountered by dentists and orthodontists when announcing oligodontia. The participants felt uncomfortable with this task and were under stress. They reported difficulties in delivering the medical information and in adapting to the message. It is essential that dental professionals develop skills in medical communication.

Novel PAX9 Mutations Causing Isolated Oligodontia.

Hypodontia, i.e., missing one or more teeth, is a relatively common human disease; however, oligodontia, i.e., missing six or more teeth, excluding the third molars, is a rare congenital disorder. Many genes have been shown to cause oligodontia in non-syndromic or syndromic conditions. In this study, we identified two novel PAX9 mutations in two non-syndromic oligodontia families. A mutational analysis identified a silent mutation (NM_006194.4: c.771G>A, p.(Gln257=)) in family 1 and a frameshift mutation caused by a single nucleotide duplication (c.637dup, p.(Asp213Glyfs*104)) in family 2. A minigene splicing assay revealed that the silent mutation resulted in aberrant pre-mRNA splicing instead of normal splicing. The altered splicing products are ones with an exon 4 deletion or using a cryptic 5' splicing site in exon 4. Mutational effects were further investigated using protein expression, luciferase activity assay and immunolocalization. We believe this study will not only expand the mutational spectrum of PAX9 mutations in oligodontia but also strengthen the diagnostic power related to the identified silent mutation.

The oligodontia phenotype in a X-linked hypohidrotic ectodermal dysplasia patient with a novel EVC2 variant.

Objectives: To analyse the pathogenic genes in a patient with hypohidrotic ectodermal dysplasia (HED) and explore the relationship between pathogenic genes and the oligodontia phenotype. Methods: Clinical data and peripheral blood were collected from a patient with HED. Pathogenic genes were analysed by whole-exon sequencing (WES) and verified by Singer sequencing. The secondary and tertiary structures of the variant proteins were predicted to analyse their toxicity. Results: The patient exhibited a severe oligodontia phenotype, wherein only two deciduous canines were left in the upper jaw. WES revealed a hemizygous EDA variant c.466C > T p.(Arg156Cys) and a novel heterozygous EVC2 variant c.1772T > C p.(Leu591Ser). Prediction of the secondary and tertiary structures of the EDA variant p.(Arg156Cys) and EVC2 variant p.(Leu591Ser) indicated impaired function of both molecules. Conclusion: The patient demonstrated a more severe oligodontia phenotype when compared with the other patients caused by the EDA variant c.466C > T. Since Evc2 is a positive regulator of the Sonic Hedgehog (Shh) signal pathway, we speculated that the EVC2 variant p.(Leu591Ser) may play a synergistic role in the oligodontia phenotype of HED, thereby exacerbating the oligodontia phenotype. Knowledge of oligodontia caused by multiple gene variants is of great significance for understanding individual differences in oligodontia phenotypes.

Characterization of novel MSX1 variants causally associated with non-syndromic oligodontia in Chinese families.

BACKGROUND: MSX1 (OMIM #142983) is crucial to normal dental development, and variants in MSX1 are associated with dental anomalies. The objective of this study was to characterize the pathogenicity of novel MSX1 variants in Chinese families with non-syndromic oligodontia (NSO). METHODS: Genomic DNA was extracted from individuals representing 35 families with non-syndromic oligodontia and was analyzed by Sanger sequencing and whole-exome sequencing. Pathogenic variants were screened via analyses involving PolyPhen-2, Sorting-Intolerant from Tolerant, and MutationTaster, and conservative analysis of variants. Patterns of MSX1-related NSO were analyzed. MSX1 structural changes suggested functional consequences in vitro. RESULTS: Three previously unreported MSX1 heterozygous variants were identified: one insertion variant (c.576_577insTAG; p.Gln193*) and two missense variants (c. 871T>C; p.Tyr291His and c. 644A>C; p.Gln215Pro). Immunofluorescence analysis revealed abnormal subcellular localization of the p.Gln193* MSX1 variant. In addition, we found that these MSX1 variants likely lead to the loss of second premolars. CONCLUSION: Three novel MSX1 variants were identified in Chinese Han families with NSO, expanding the MSX1 variant spectrum and presenting a genetic origin for the pathogenesis detected in patients and their families.

Whole genome sequencing in families with oligodontia.

BACKGROUND/OBJECTIVES: Tooth agenesis (TA) is among the most common malformations in humans. Although several causative mutations have been described, the genetic cause often remains elusive. Here, we test whether whole genome sequencing (WGS) could bridge this diagnostic gap. METHODS: In four families with TA, we assessed the dental phenotype using the Tooth Agenesis Code after intraoral examination and radiographic and photographic documentation. We performed WGS of index patients and subsequent segregation analysis. RESULTS: We identified two variants of uncertain significance (a potential splice variant in PTH1R, and a 2.1 kb deletion abrogating a non-coding element in FGF7) and three pathogenic variants: a novel frameshift in the final exon of PITX2, a novel deletion in PAX9, and a known nonsense variant in WNT10A. Notably, the FGF7 variant was found in the patient, also featuring the WNT10A variant. While mutations in PITX2 are known to cause Axenfeld-Rieger syndrome 1 (ARS1) predominantly featuring ocular findings, accompanied by dental malformations, we found the PITX2 frameshift in a family with predominantly dental and varying ocular findings. CONCLUSION: Severe TA predicts a genetic cause identifiable by WGS. Final exon PITX2 frameshifts can cause a predominantly dental form of ARS1.

Oligodontia in the Clinical Spectrum of Syndromes: A Systematic Review.

The aim of this systematic review was to describe the clinical and genetic features of syndromes showing oligodontia as a sign. The review was performed according to the PRISMA 2020 checklist guidelines, and the search was conducted using PubMed, Scopus, Lilacs, Web of science, Livivo, and EMBASE and supplemented by a gray literature search on Google Scholar and ProQuest, applying key terms relevant to the research questions. The systematic review identified 47 types of syndromes in 83 studies, and the most common was hypohidrotic ectodermal dysplasia, which was reported in 24 patients in 22 studies. Other common syndromes that reported oligodontia included Axenfeld-Rieger syndrome, Witkop's syndrome, Ellis-van Creveld syndrome, blepharocheilodontic syndrome, and oculofaciocardiodental syndrome. The X-linked mode of inheritance was the most reported (n = 13 studies), followed by the autosomal dominant (n = 13 studies). The review describes the main syndromes that may have oligodontia as a clinical sign and reinforces the need for orodental-facial examining for adequate diagnosis and treatment of the affected patients. Molecular analysis in order to better understand the occurrence of oligodontia is imperative.

Orthodontic Treatment of Palatally Impacted Canines in Severe Non-Syndromic Oligodontia with the Use of Mini-Implants: A Case Report.

Background: The risk of palatally displaced canines (PDCs) rises in patients with tooth agenesis. The orthodontic extrusion and alignment of PDCs require adequate anchorage to enable tooth movement and control the side effects. There is no paper presenting treatment in the case of severe oligodontia with simultaneous PDCs and the use of mini-implants (MIs) for their orthodontic extrusion. Case presentation: A 15-year-old patient presented with non-syndromic oligodontia and bilateral PDCs. Cone beam computed tomography revealed that both PDCs were in proximity to the upper incisors' roots. There was no evident external root resorption of the incisors. The "canines first" approach was chosen. MIs were used both as direct and indirect anchorage. First, the extrusive forces of cantilevers were directed both occlusally and distally. Next, the buccal directions of forces were implemented. Finally, fixed appliances were used. PDCs were extruded, aligned, and torqued. Proper alignment and occlusion were achieved to enable further prosthodontic restorations. Conclusions: The use of MIs made it possible to avoid collateral effects, reduce the risk of complications, and treat the patient effectively. MIs provide adequate anchorage in demanding cases. The use of MIs for the extrusion of PDCs made it possible to offer this treatment option to patients with severe oligodontia. The presented protocol was effective and served to circumvent treatment limitations associated with an inadequate amount of dental anchorage and a high risk of root resorption.

Global Trends and Hotspots in Research on Tooth Agenesis: A 20-Year Bibliometric Analysis.

Tooth agenesis, one of the most common developmental defects in humans, not only impairs oral function but can also lead to craniofacial deformities. Bibliometric analysis can reveal significant shifts in research and publishing trends within specific fields. This study aims to provide a comprehensive overview of the research hotspots in tooth agenesis and predict future trends through bibliometric analysis. We searched for English-language publications related to tooth agenesis from 2001 to 2021 on the Web of Science. The publications were limited to original and review articles, and bibliometric parameters such as publication year, country, institution, author, journal, citations, and keywords were extracted and analyzed using VOSviewer, Microsoft Excel 2010, and CiteSpace. A total of 2,287 papers were ultimately selected. The results show that the USA holds a leading position in the field of tooth agenesis research. A total of 9,803 authors participated in these studies, with Alexandre R Vieira from the USA being the most prolific and most cited author. This study indicates that multidisciplinary management has become the consensus first choice for treating dental agenesis. Gene mutations related to tooth agenesis continue to be a research hotspot attracting scholarly attention. Exploring the relationship between tooth agenesis and cancer may be a future research direction. These findings contribute to potential collaborations among experts in future research on the genetic causes of tooth agenesis and tumor development and to assist the scientific community by identifying research gaps in this field.

New observation of severe tooth malformation in a female patient with ectodermal dysplasia due to the EDA splice acceptor variant c.742-2A>G.

BACKGROUND: Ectodermal dysplasias are inherited disorders, which are characterized by congenital defects in two or more ectodermal structures such as skin, sweat glands, hair, nails, teeth, and mucous membranes. METHOD: Here, we describe a new observation of significant oligodontia in a female patient with the EDA gene variant c.742-2A>G. RESULTS: The results strongly suggest that the EDA gene variant c.742-2A>G is pathogenic. The oligodontia in the proband was exceptionally severe. CONCLUSION: We demonstrate that the very rare splice acceptor variant EDA c.742-2A>G is associated with severe oligodontia even in females. Our study points that this variant is pathogenic. An early identification of this variant is crucial for planning adequate treatment and follow-up in time by a multidisciplinary team.