Treatment and genetic analysis of multiple supernumerary and impacted teeth in an adolescent patient.

BACKGROUND: Multiple supernumerary teeth, combined with numerous impacted teeth, can lead to various malocclusions, posing significant treatment challenges. While certain genes associated with syndromic cases of multiple supernumerary and impacted teeth have been identified, the etiologies of non-syndromic cases still largely remain elusive. CASE PRESENTATION: Here, we report a treatment of a 12-year-old boy who presented with 10 supernumerary teeth and 6 impacted teeth, accompanied by a genetic analysis to explore the underlying etiology. During the treatment, fifteen teeth were extracted, and various skilled techniques, including the closed-eruption technique and the application of by-pass arches, were utilized. Post-treatment, traction was successful for all the impacted teeth, without any tooth mobility or reduction in gingival height. Space closure, well-aligned teeth, and excellent functional occlusion were achieved. Furthermore, comprehensive genetic analysis was conducted through whole-exome sequencing on the patient and his parents, which revealed a potential link between the patient's numerous supernumerary teeth and abnormal mineralization. Notably, the p.Ser496Pro variant in the TCF7L2 gene was identified as a potential candidate variant in this patient. CONCLUSIONS: Overall, our findings not only report the treatment of a rare case involving multiple supernumerary and impacted teeth but also offer valuable insights into the molecular basis of supernumerary teeth.

Investigation of the expression level of long non-coding RNAs in dental follicles of impacted mandibular third molars.

OBJECTIVES: Dental follicle (DF) is made up of mesenchymal cells and fibers surrounding the enamel organ of a developing tooth. It has been shown that cystic and neoplastic lesions can develop from the pericoronal follicles of impacted third molars (ITMs). But the molecular transformation of DF tissues has not yet been uncovered and remains elusive. Accordingly, in the present study, we aimed to investigate the differential expression of lncRNA genes in DF tissues associated with asymptomatic impacted mandibular third molars (IMTMs) that do not show pathological pericoronal radiolucency in radiographic examination. MATERIAL AND METHODS: A total of 30 patients with unilateral mesioangular IMTMs were enrolled for the study. The expressions of lncRNA genes were determined in the DF and healthy gingival tissues obtained from study patients. For the determination of lncRNA expression levels, RNA was isolated from the obtained tissues, converted to cDNA samples, and analyzed by quantitative real-time PCR method. RESULTS: As a result, we found that the gene expression of MEG3 was increased about 10-fold in DF tissues compared to healthy gingival tissues (p < 0.0001). In addition, NORAD expression was found to be upregulated 4.2-fold (p = 0.0002) in DF tissues. Also, expression level of MALAT1 was found to be decreased 1.24-fold (p = 0.584) and TP73-AS1 increased 2.6-fold (p = 0.093) in DF tissues compared to healthy gingival tissues. CONCLUSIONS: Consequently, present findings suggest that differentially expressed lncRNAs in DFs might be associated with the various levels of cellular events including osteogenic differentiation, DNA damage, and the transformation into odontogenic pathology. CLINICAL RELEVANCE: Expression levels of MEG3 and NORAD lncRNA molecules may guide clinicians in the evaluation of asymptomatic ITM dental follicles that cannot be determined radiologically and during extraction of these teeth for prophylactic purposes.

Genetic Pattern, Orthodontic and Surgical Management of Multiple Supplementary Impacted Teeth in a Rare, Cleidocranial Dysplasia Patient: A Case Report.

Background: Cleidocranial dysplasia (CCD) is a rare, autosomal dominant skeletal dysplasia with a prevalence of one per million births. The main causes of CCD are mutations in the core-binding factor alpha-1 (CBFA1) or runt-related transcription factor-2 (RUNX2), located at the 6p21 chromosomal region. RUNX2 plays important roles in osteoblast differentiation, chondrocyte proliferation and differentiation, and tooth formation. The disease is characterized by clavicular aplasia or hypoplasia, Wormian bones, delayed closure of cranial suture, brachycephalic head, maxillary deficiency, retention of primary teeth, inclusion of permanent teeth, and multiple supernumerary teeth. Materials and Methods: A 22-year-old girl suffering from cleidocranial dysplasia with short stature, narrow shoulders, craniofacial manifestations (short face, broad forehead, etc.) and dental anomalies (different lower dental elements under eruption, supernumerary and impacted multiple teeth, etc.) was examined at our service (Complex Operative Unit of Odontostomatology of Policlinico of Bari). RX Orthopantomography (OPG) and cone beam computed tomography (CBCT) were requested to better assess the position of the supernumerary teeth and their relationships with others and to evaluate the bone tissue. Results: Under eruption was probably caused by dental interferences with supernumerary teeth; hence, extractions of supernumerary upper canines and lower premolars were performed under general anaesthesia. Surgery outcome was excellent with good tissue healing and improvements in the therapeutic possibilities with future orthodontics. Conclusions: The objective of this article is to give an update about radiological, clinical, and molecular features of CCD and to alert the health team about the importance of establishing an early diagnosis and an appropriate treatment in these patients to prevent impacted teeth complications and to offer them a better quality of life.

Role of polymorphisms of MSX1 and PAX9 genes in palatal impaction of maxillary canines.

OBJECTIVE: Maxillary canines are the second-most commonly impacted teeth. About two-thirds of the impacted maxillary canines are palatally impacted. Studies in the past have shown that 40% of cases with palatal impaction of maxillary canines presented with agenesis of third molars. Sporadic agenesis of third molars have been associated with polymorphisms in the MSX1 and PAX9 genes. The present study aims at evaluating the association between polymorphisms of PAX9, MSX1 and palatally impacted canines in a random population sample. DESIGN AND SETTING: Fifty individuals with palatally impacted maxillary canines and 50 gender and age-matched controls were included in this study. METHODS: Single nucleotide polymorphisms (SNPs), rs12532 of MSX1 and rs2073247 of PAX9, were genotyped using polymerase chain reaction and restriction fragment length polymorphism. The significance of the differences among the groups was assessed by odds ratio and Chi-squared test with a 95% confidence interval. RESULTS: Single nucleotide polymorphisms rs12532 [MSX1] and rs 2073247 [PAX9] showed a statistically significant association with palatal impaction of maxillary canines. In addition, the combined presence of the AG/CT genotypes of these genes in an individual caused a significant increase in the risk for palatal impaction. CONCLUSION: These results suggest that the rs12532 and rs2073247 polymorphisms of genes MSX1 and PAX9 are positively associated with palatal impaction of maxillary canines. Future studies investigating various other SNPs of these genes in a larger sample of different populations could provide clinching details.

Gene expression profiles in dental follicles from patients with impacted canines.

Animal studies suggest that the dental follicle (DF) plays a major role in tooth eruption. However, the role of the DF during tooth impaction and related root resorptions in adjacent teeth is not clear. The hypothesis for the present study is that expression of regulatory factors involved in the bone remodelling process necessary for tooth eruption may differ between dental follicles from teeth with different clinical situations. We have analysed the gene expression profiles in the DF obtained from impacted canines, with (N = 3) or without (N = 5) signs of root resorption, and from control teeth (normal erupting teeth, mesiodens) (N = 3). DF from 11 patients (mean age: 13 years) obtains at the time of surgical exposure of the tooth. Due to the surgical time point, all teeth were in a late developmental stage. Gene expression related to osteoblast activation/bone formation, osteoclast recruitment and activation was analysed by RTqPCR. Genes related to bone formation (RUNX2, OSX, ALP, OCN, CX43) were highly expressed in all the samples, but osteoclast recruitment/activation markers (OPG, RANKL, MCP-1, CSF-1) were negligible. No apparent patterns or significant differences in gene expression were found between impacted canines, with or without signs of root resorption, or when compared to control teeth. Our results suggest the DF regulation of osteoclastic activity is limited in the late pre-emergent stage of tooth development, irrespective if the tooth is normally erupting or impacted. We suggest that the follicle may have an important regulatory function for alveolar bone formation in the final eruption process and CX43-gap junction communication could be an important signalling pathway.

Extending Genome-Wide Association Study Results to Test Classic Anthropological Hypotheses: Human Third Molar Agenesis and the "Probable Mutation Effect".

A genome-wide association study (GWAS) identifies regions of the genome that likely affect the variable state of a phenotype of interest. These regions can then be studied with population genetic methods to make inferences about the evolutionary history of the trait. There are increasing opportunities to use GWAS results-even from clinically motivated studies-for tests of classic anthropological hypotheses. One such example, presented here as a case study for this approach, involves tooth development variation related to dental crowding. Specifically, more than 10% of humans fail to develop one or more permanent third molars (M3 agenesis). M3 presence/absence variation within human populations has a significant genetic component (heritability estimate h 2 = 0.47). The evolutionary significance of M3 agenesis has a long history of anthropological speculation. First, the modern frequency of M3 agenesis could reflect a relaxation of selection pressure to retain larger and more teeth following the origins of cooking and other food-softening behaviors (i.e., the genetic drift hypothesis or, classically, the "probable mutation effect"). Alternatively, commensurate with increasing hominin brain size and facial shortening, M3 agenesis may have conferred an adaptive fitness advantage if it reduced the risk of M3 impaction and potential health complications (i.e., the positive selection hypothesis). A recent GWAS identified 70 genetic loci that may play a role in human M3 presence/absence variation. To begin evaluating the contrasting evolutionary scenarios for M3 agenesis, we used the integrated haplotype score (iHS) statistic to test whether those 70 genetic regions are enriched for genomic signatures of recent positive selection. None of our findings are inconsistent with the null hypothesis of genetic drift to explain the high prevalence of human M3 agenesis. This result might suggest that M3 impaction rates for modern humans do not accurately retrodict those of the preagricultural past. Alternatively, the absence of support for the positive selection hypothesis could reflect a lack of power; this analysis should be repeated following the completion of more comprehensive GWAS analyses for human M3 agenesis.

Etiology of maxillary canine impaction: a review.

This article is a review that enumerates the causes of impaction of the maxillary permanent canines, including hard tissue obstructions, soft tissue lesions, and anomalies of neighboring teeth, and discusses the much-argued relationship between environmental and genetic factors. These phenomena have been shown in many investigations to accompany the diagnosis of canine impaction and have been presented as unrelated anomalous features, each of which is etiologically construed as genetic, including the aberrant canine itself. While in general the influence of genetics pervades the wider picture, a guidance theory proposes an alternative etiologic line of reasoning and interpretation of these studies, in which the same genetically determined anomalous features provide an abnormal milieu in which the canine is reared and from which it is guided in its misdirected and often abortive path of eruption.

Transcriptome Sequencing of Gingival Tissues from Impacted Third Molars Patients Reveals the Alterations of Gene Expression.

OBJECTIVE: The removal of impacted third molars by surgery may occur with a series of complications, whereas limited information about the postoperative pathogenesis is available. The objective of this study is to identify changes in gene expression after flap surgical removal of impacted third molars and provide potential information to reduce postoperative complications. METHODS: The gingival tissues of twenty patients with flap surgical removal of impacted third molars and twenty healthy volunteers were collected for gene expression testing. The collected gingival tissues were used RNA sequencing technology and quantitative real-time PCR validation was performed. DEG was mapped to protein databases such as GO and KEGG for functional annotation and, based on annotation information, for mining of differential expression genes in patients with mpacted third molars. RESULTS: A total of 555 genes were differentially expressed. Among the top up-regulated genes, HLA-DRB4, CCL20, and CXCL8 were strongly associated with immune response and signal transduction. Among the top down-regulated genes, SPRR2B, CLDN17, LCE3D and LCE3E were related to keratinocyte differentiation, IFITM5, and BGLAP were related to bone mineralization, UGT2B17 is associated with susceptibility to osteoporosis. KEGG results showed that the DEGs were related to multiple disease-related pathways. CONCLUSION: This first transcriptome analysis of gingival tissues from patients with surgical removal of impacted third molars provides new insights into postoperative genetic changes. The results may establish a basis for future research on minimizing the incidence of complications after flap-treated third molars.

Linkage analysis confirms heterogeneity of hereditary gingival fibromatosis.

OBJECTIVES: Hereditary Gingival Fibromatosis (HGF) is a rare benign fibrous lesion of the gingival tissues presumably caused by single gene defects. The aim of this study was to identify the genetic defect leading to HGF in an extended pedigree. MATERIALS AND METHODS: We report the clinical features and genetic analysis of a family affected by HGF. A total of 17 subjects were assessed clinically and had blood samples taken for DNA extraction. Multipoint parametric linkage analysis was performed to identify the possible chromosomal location responsible for HGF in this family. RESULTS: Presence of severe HGF associated with tooth impaction was confirmed for seven members of this three-generation family. Linkage analysis revealed that loci on chromosomes 7, 10, 13, 15, 16, 17, 19 and 20 were linked to this trait. Previously found mutations in the SOS1 and GINGF loci were therefore excluded by this analysis. CONCLUSIONS: This study brings further evidence for genetic heterogeneity of HGF and points towards the existence of different, not-yet-identified genes linked to this condition.

Establishing the diagnostic criteria for eruption disorders based on genetic and clinical data.

INTRODUCTION: Proper diagnosis and management of eruption disturbances remains challenging but is critical to a functional occlusion. The objective of this study was to establish definitive criteria to differentiate and diagnose eruption disorders, specifically primary failure of eruption (PFE) and ankylosis. METHODS: Sixty-four affected persons were placed into 3 cohorts: PFE diagnosed through confirmed PTH1R mutation (n = 11), PFE diagnosed based on clinical criteria (n = 47), and ankylosis diagnosed based on clinical criteria (n = 6). These groups were assessed to identify clinical features that differentiate PFE and ankylosis. RESULTS: Ninety-three percent of the subjects in the genetic and clinical PFE cohorts combined (n = 58) and 100% in the genetic PFE cohort had at least 1 infraoccluded first permanent molar. Additionally, a novel functional PTH1R mutation, 1092delG, was identified and linked to PFE in the deciduous dentition. CONCLUSIONS: An infraoccluded, supracrestal first molar is a hallmark of PFE, often involving both arches in the permanent or deciduous dentition, and with unilateral or bilateral affection, infraoccluded second premolar or second molar, and multiple affected adjacent teeth. Our results further suggest that PFE and ankylosis might be clinically indistinguishable without knowledge of prior trauma, treatment history, genetic information, or obliteration of the periodontal ligament space.

Triplets with bilateral palatally displaced canines in association with third molar agenesis: an example of biologically related dental anomaly patterns?

This case series shows male triplets with similarly positioned palatally displaced canines and agenesis of third molars. It supports findings reported previously in the literature suggesting a genetic origin for the palatally displaced canine and other dental anomalies which may be biologically related.

Cleidocranial dysplasia: oral features and genetic analysis of 11 patients.

BACKGROUND: Cleidocranial dysplasia (CCD) is a dominantly inherited autosomal disease characterized by typical bone defects including short stature, persistently open or delayed closure of the cranial sutures, and hypoplastic or aplastic clavicles. Oral features are frequent and include supernumerary teeth, delayed eruption or impaction of the permanent teeth, and malocclusion. Heterozygous mutations in RUNX2 gene, which encodes a transcription factor essential for osteoblast differentiation, were identified as the etiological cause of CCD. OBJECTIVE AND METHODS: Herein, we performed physical and radiographic examination and screening for RUNX2 mutations in 11 patients from five families with CCD. RESULTS: All patients demonstrated the classical phenotypes related to CCD. Families whose affected members had several dental alterations such as multiple impacted and supernumerary teeth demonstrated heterozygous missense mutations (R190Q and R225Q) that impair the runt domain of RUNX2. On the other hand, CCD patients from families with low frequency of dental abnormalities showed no mutation in RUNX2 or mutation outside of the runt domain (Q292fs→X299). CONCLUSION: The current findings suggest a correlation between dental alterations and mutations in the runt domain of RUNX2 in CCD patients. Further clinical and genetic studies are needed to clarify the relationship between phenotypes and genotypes in CCD and to identify other factors that might influence the clinical features of this uncommon disease.

Differing therapeutic approaches to cleidocranial dysplasia (CCD).

Cleidocranial dysplasia (CCD) (MIM 119600) is a genetic skeletal disorder characterised by skeletal alterations at numerous bone segments (cranium, clavicles, pelvis) and a typical hyperdontia. It is a hereditary disease of the dominant autosomal type with wide variability of expression. The constant presence of numerous supernumerary teeth poses two orders of problems. On one hand, if these supplementary teeth are impacted, they may constitute a mechanical obstacle to the eruption of normal teeth. If on the contrary they have erupted, they cause aesthetic and functional damage. Surgical therapy is indispensable to restore a correct architecture to the alveolar-dental arches, and it is recommended during childhood to avoid or at least reduce complications in adulthood. Two cases of cleidocranial dysplasia are here reported. The adult patient (Case 1), reached our observation with a poor oral situation, manifested relapsing odontogenic abscesses at several impacted supernumerary teeth. The surgical treatment was complex and invasive, requiring percutaneous access in order to remove a tooth embedded in the mandible and the extraction of almost all residual teeth. This outcome was avoided in the second case, through combined surgical-orthodontic treatment that entailed extraction of the supernumerary teeth and subsequent orthodontic treatment, with restoration of a normal occlusion. In conclusion, management of patients suffering from very rare pathologies should be carefully evaluated in relation to clinical characteristics and possible local and systemic complications. The aim of this study is to illustrate two cases managed in a paradigmatically opposite way. It is paramount for the surgeon to intercept cases of hyperodontia typical of CCD at an early phase. It is possible, through correct surgical-orthodontic treatment, not only to avoid local and general complications, but also to achieve proper occlusion.

Non-coding RNAs transcribed from ultra-conserved regions (T-UCRs) are differentially expressed in dental follicle tissues of impacted mandibular third molars.

INTRODUCTION: Transcribed ultra-conserved regions (T-UCRs) are a new class of long non-coding RNA molecules transcribed from ultra-conserved regions (UCRs) of the human genome. T-UCRs are extremely conserved in the human, rat, and mouse genomes. Deletions of genomic areas containing UCRs resulted in live mice that developed without distinguishable phenotypes, implying that T-UCRs are involved in developmental processes. In addition, there is increasing evidence that dental follicle tissues exhibit various cellular alterations involving deregulation of protein-coding genes and non-coding RNAs. Accordingly, the main objective of the present study was to determine the clinical significance and distinct expression signatures of non-coding RNA molecules transcribed from ultra-conserved regions in dental follicle tissues of impacted mandibular third molars. MATERIALS AND METHODS: From March 2021 to December 2021, a total of 42 patients who referred to clinic of oral and maxillofacial surgery department with the indications of impacted mandibular third molar extraction from 38th and 48th positions were enrolled for the study. For the analysis of T-UCR expression levels, real-time quantitative reverse transcription PCR method was used. RESULTS: Findings of the present study indicated that T-UCRs are distinctly expressed in dental follicle tissues of impacted mandibular third molars. The expression of uc.38, uc.112, and uc.338 was found to be significantly increased in the dental follicles of impacted mandibular third molars, indicating a clinical significance of these molecules. In addition, no differences in T-UCR expression were found as a function of demographic characteristics. CONCLUSIONS: Collectively, transcribed ultra-conserved elements, such as uc.38, uc.112, and uc.338, are considerably deregulated in the dental follicle tissues of impacted mandibular third molars and might be responsible for the molecular changes acquired by dental follicle tissues of impacted mandibular third molars.

Requirement of alveolar bone formation for eruption of rat molars.

Tooth eruption is a localized event that requires a dental follicle (DF) to regulate the resorption of alveolar bone to form an eruption pathway. During the intra-osseous phase of eruption, the tooth moves through this pathway. The mechanism or motive force that propels the tooth through this pathway is controversial but many studies have shown that alveolar bone growth at the base of the crypt occurs during eruption. To determine if this bone growth (osteogenesis) was causal, experiments were designed in which the expression of an osteogenic gene in the DF, bone morphogenetic protein-6 (Bmp6), was inhibited by injection of the first mandibular molar of the rat with a small interfering RNA (siRNA) targeted against Bmp6. The injection was followed by electroporation to promote uptake of the siRNA. In 45 first molars injected, eruption was either delayed or completely inhibited (seven molars). In the impacted molars, an eruption pathway formed but bone growth at the base of the crypt was greatly reduced compared with the erupted first-molar controls. These studies show that alveolar bone growth at the base of the crypt is required for tooth eruption and that Bmp6 may be essential for promoting this growth.

Incidence and effects of genetic factors on canine impaction in an isolated Jewish population.

INTRODUCTION: The etiology of palatal canine impaction is multifactorial and includes a genetic contribution. The aim of this study was to find the incidence and effects of genetic factors on palatally impacted canines in a genetically isolated community of ultraorthodox Hassidic Jews of Ashkenazi decent. METHODS: For this study, we retrospectively evaluated 1000 charts of Hassidic Jewish patients. Their distribution was 58% female and 42% male, with a mean age of 14 years. RESULTS: From those patients, 49 (4.9%) were determined to have canine impaction. Of these 49, 69.4% had unilateral palatal impaction, 26.5% had bilateral palatal impaction, and 4.1% had unilateral labial impaction. The z-test of proportion showed that female patients have a greater percentage than males for unilateral palatal impaction (P <0.01) with left-side dominance (P <0.01). CONCLUSIONS: Our results imply that genetics plays a significant role in maxillary canine palatal impaction. A genetically isolated Hassidic Jewish community can be a useful group to study the effects of genetic factors on various dental anomalies, including palatally displaced canines.

Multiple hyperdontia: Report of an unusual case.

Supernumerary teeth are an infrequent developmental anomaly that can appear in any area of the dental arch and can affect any dental organ. Multiple supernumerary teeth, or hyperdontia, is rare in people with no other associated diseases or syndromes. Conditions commonly associated with hyperdontia include cleft lip and palate, trichorhinophalangeal syndrome, cleidocranial dysplasia, and Gardner's syndrome. A black girl, aged 11 years 8 months, came for consultation; radiographs showed 81 teeth: 18 deciduous, 32 permanent, and 31 supernumerary. The main concern initially was to determine whether she was syndromic, and she was referred to a geneticist. G banding analysis showed pericentric inversion of chromosome 9; the chromosome formula was 46, XX, inv (9) (p13q21). Orthodontic treatment for this patient will be a clinical challenge because of the great number of teeth to be extracted and the alterations in the shapes of the teeth. Treatment goals should be established by a multidisciplinary team, where oral surgeon, orthodontist, periodontist, and prosthodontist come together to solve a medical and dental puzzle, eliminating the pieces that do not fit and searching for new ones to obtain an occlusion that will give the patient physiologic conditions of normality and esthetic satisfaction.

Mandibular second molar impaction. Part I: Genetic traits and characteristics.

INTRODUCTION: Detection of mandibular second molar (MM2) impaction is imperative for orthodontic diagnosis and treatment. In this study, we examined a possible genetic trait in MM2 impaction in 2 populations and defined distinctive characteristics. METHODS: Initial panoramic radiographs of patients of Israeli (n = 3500) and Chinese-American (n = 3000) origin, aged 11 to 15 years, were examined. Twelve distinctive characteristics were compared between the unilateral impacted and the nonimpacted sides. RESULTS: A total of 120 subjects with MM2 impaction were found (1.8%). The Chinese-American population had a higher prevalence (n = 71, 2.3%) of MM2 impaction compared with the Israeli population (n = 49, 1.4%; P = 0.004). For the subjects with MM2 impaction, the Israelis had significantly (P = 0.039) fewer bilateral impactions (27%) than did the Chinese-Americans (45%). Mesially inclined impacted MM2s were more common (88% and 89%) in the Israeli and Chinese-American populations, respectively. The unilateral impacted side demonstrated reductions in the distance between the mandibular first molar and the ramus (P <0.001), the length of the mesial root of the MM2 (P <0.001), and the height between the MM2 and the mandibular third molar, and increases in the angulations of the MM2 (P <0.001) and the mandibular third molar (P <0.003). CONCLUSIONS: An autosomal genetic trait is present in MM2 impaction with greater penetrance in the Chinese-American population. Within developmental impediments, the deficient mesial root length of the MM2 is the primary impaction factor.

Association of Polymorphic and Haplotype Variants of the MSX1 Gene and the Impacted Teeth Phenomenon.

It is known that genetic factors determine odontogenesis; furthermore, studies have revealed that various genes in humans can regulate the development of different types and generations of teeth. In this study it has been assumed that tooth impaction-at least to some extent-also depends on the presence of specific genetic markers, especially allelic variants of the MSX1 gene. The primary objective of the study was to evaluate the suitability of selected molecular markers located within the MSX1 gene for the determination of the risk of tooth impaction in particular patients. The study participants were divided into two groups: (1) the study group-at least one secondary tooth was impacted in the jaws; (2) the control group-no impacted tooth in the jaws. Real-Time PCR and TaqMan probes were used to detect selected polymorphisms in the analyzed genes. Two single nucleotide polymorphisms of MSX1 were analyzed. After the two subgroups of patients were distinguished in the study group based on the number of impacted teeth, statistically significant differences in the frequency of genotypes described for rs12532 in the MSX1 gene were found.

Supernumerary impacted teeth in a patient with SOX2 anophthalmia syndrome.

SOX2 anophthalmia syndrome characteristically presents as anophthalmia or microphthalmia, with various extraocular symptoms, such as hypogonadotropic hypogonadism, brain anomaly, and esophageal abnormalities. In this report, we describe a patient with SOX2 anophthalmia syndrome complicated with a dental anomaly, multiple supernumerary impacted teeth, and persistence of deciduous teeth. Multiple supernumerary teeth are usually not solitary symptoms, but indicate systemic syndrome such as cleidocranial dysplasia. In odontogenesis, many transcriptional factors, such as BMPs, FGFs, and Wnts, play significant roles and SOX2 is known to interact with some of them. The role of SOX2 in dental development remains unknown, however, multiple supernumerary teeth can be considered as extraocular symptoms of SOX2 anophthalmia syndrome, rather than the coincidence of two rare diseases.