Abnormal Tooth Eruption Research Articles

Fahr’s Syndrome with Pseudohypoparathyroidism: Oral Features and Genetic Insights

Fahr’s syndrome is a rare neurodegenerative disorder with limited research on its oral manifestations. This study investigates the dental features and genetic background of Fahr’s syndrome through a pedigree analysis and a retrospective literature study. A clinical examination and whole-exome sequencing (WES) were conducted on a female patient with Fahr’s syndrome and pseudohypoparathyroidism, along with her family members. The patient presented with super-numerary teeth, tooth agenesis, enamel hypoplasia, and abnormal tooth eruption. The WES did not reveal any known pathogenic mutations related to pseudohypoparathyroidism or Fahr’s disease. However, genetic variations in KIF1A, FZD8, and PDGFA may underlie these dental abnormalities. Additionally, a retrospective analysis of 22 reported cases from PubMed and the Human Gene Mutation Database (1 January 1965–30 June 2024) was conducted with keywords such as “Fahr’s disease”, “Fahr’s syndrome”, “dental”, and “hypoparathyroidism”. The analysis showed that patients with Fahr’s syndrome, pseudohypoparathyroidism, and idiopathic hypoparathyroidism exhibited similar oral abnormalities, including tooth agenesis, root dysplasia, dental malformations, and abnormal tooth eruption. Variations in the incidence of tooth agenesis and dental malformation among these groups may be linked to differences in parathyroid hormone metabolism. These findings suggest oral abnormalities are the key local features of Fahr’s syndrome and related parathyroid disorders.

A Deep-learning System for Diagnosing Ectopic Eruption

Objectives: To construct a diagnostic model for mixed dentition using a multistage deep-learning network to predict potential ectopic eruption in permanent teeth by integrating dentition segmentation into the process of automatic classification of dental development stages.Methods: A database was established by reviewing 1576 anonymous panoramic radiographs of children aged 6–12 years, collected at the Stomatology Hospital, xxxxxx. These radiographs were categorised as normal or ectopic eruption, with expert diagnoses serving as a benchmark for training and evaluating artificial intelligence (AI) models. Furthermore, tooth boundaries and dental development stages were manually annotated by three pediatric dentistry experts. The dataset was split into training, validation, and test sets at an 8:1:1 ratio.Results: The diagnostic performance of the deep-learning model was rigorously evaluated. The model demonstrated accuracy in tooth segmentation, with Intersection over Union, precision, sensitivity, and F1 scores of 0.959, 0.993, 0.966, and 0.979, respectively. Furthermore, its ability to identify tooth ectopic eruptions on panoramic radiographs, when compared to evaluations by three dentists. Based on McNemar's test, the model's specificity and accuracy in identifying ectopic tooth eruptions on the test dataset surpassed that of Dentist 1 (P < 0.05), while no significant difference was observed compared to the other two dentists. Besides, the deep learning model also showed its potential in classifying dental development stages, as tested against three different standards.Conclusions: The adaptability of the AI-enabled model in this study was demonstrated across multiple scenarios, with clinical validation highlighting its efficacy in diagnosing ectopic eruptions using a multistage deep-learning approach.Clinical Significance: Our findings provide new insights and technical support for the prevention and treatment of abnormal tooth eruption, laying the groundwork for predictive models for other prevalent pediatric dentistry conditions.

Abnormal dental follicle cells: A crucial determinant in tooth eruption disorders (Review).

The dental follicle (DF) plays an indispensable role in tooth eruption by regulating bone remodeling through their influence on osteoblast and osteoclast activity. The process of tooth eruption involves a series of intricate regulatory mechanisms and signaling pathways. Disruption of the parathyroid hormone‑related protein (PTHrP) in the PTHrP‑PTHrP receptor signaling pathway inhibits osteoclast differentiation by DF cells (DFCs), thus resulting in obstructed tooth eruption. Furthermore, parathyroid hormone receptor‑1 mutations are linked to primary tooth eruption failure. Additionally, the Wnt/β‑catenin, TGF‑β, bone morphogenetic protein and Hedgehog signaling pathways have crucial roles in DFC involvement in tooth eruption. DFC signal loss or alteration inhibits osteoclast differentiation, affects osteoblast and cementoblast differentiation, and suppresses DFC proliferation, thus resulting in failed tooth eruptions. Abnormal tooth eruption is also associated with a range of systemic syndromes and genetic diseases, predominantly resulting from pathogenic gene mutations. Among these conditions, the following disorders arise due to genetic mutations that disrupt DFCs and impede proper tooth eruption: Cleidocranial dysplasia associated with Runt‑related gene 2 gene mutations; osteosclerosis caused by CLCN7 gene mutations; mucopolysaccharidosis type VI resulting from arylsulfatase B gene mutations; enamel renal syndrome due to FAM20A gene mutations; and dentin dysplasia caused by mutations in the VPS4B gene. In addition, regional odontodysplasia and multiple calcific hyperplastic DFs are involved in tooth eruption failure; however, they are not related to gene mutations. The specific mechanism for this effect requires further investigation. To the best of our knowledge, previous reviews have not comprehensively summarized the syndromes associated with DF abnormalities manifesting as abnormal tooth eruption. Therefore, the present review aims to consolidate the current knowledge on DFC signaling pathways implicated in abnormal tooth eruption, and their association with disorders of tooth eruption in genetic diseases and syndromes, thereby providing a valuable reference for future related research.

Research progress in regional odontodysplasia

Regional odontodysplasia (ROD) is a rare localized dental developmental anomaly. The typical clinical manifestations of ROD are abnormal tooth eruption, abnormal development of enamel and dentin. The radiographic characteristic is "ghost teeth". Its etiology still remains unknown. The care and treatment of a patient with ROD needs a multidisciplinary approach. And the treatment should be taken after the assessment of each individual case of ROD. This paper reviews the definition, etiology, epidemiological features, clinical manifestations, imaging features, dental microstructure and treatment strategies of ROD to provide reference for clinical diagnosis and treatment.

Identification of a novel heterozygous PTH1R variant in a Chinese family with incomplete penetrance.

Mutations in PTH1R are associated with Jansen-type metaphyseal chondrodysplasia (JMC), Blomstrand osteochondrodysplasia (BOCD), Eiken syndrome, enchondroma, and primary failure of tooth eruption (PFE). Inheritance of the PTH1R gene can be either autosomal dominant or autosomal recessive, indicating the complexity of the gene. Our objective was to identify the phenotypic differences in members of a family with a novel PTH1R mutation. The proband was a 13-year, 6-month-old girl presenting with short stature, abnormal tooth eruption, skeletal dysplasia, and midface hypoplasia. The brother and father of the proband presented with short stature and abnormal tooth eruption. High-throughput sequencing was performed on the proband, and the variant was confirmed in the proband and other family members by Sanger sequencing. Amino acid sequence alignment was performed using ClustalX software. Three-dimensional structures were analyzed and displayed using the I-TASSER website and PyMOL software. High-throughput genome sequencing and Sanger sequencing validation showed that the proband, her father, and her brother all carried the PTH1R (NM_000316) c.1393G>A (p.E465K) mutation. The c.1393G>A (p.E465K) mutation was novel, as it has not been reported in the literature database. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, the p.E465K variant was considered to have uncertain significance. Biological information analysis demonstrated that this identified variant was highly conserved and highly likely pathogenic. We identified a novel heterozygous mutation in the PTH1R gene leading to clinical manifestations with incomplete penetrance that expands the spectrum of known PTH1R mutations.

Analysis of amelogenesis imperfecta with abnormal tooth eruption caused by FAM83H mutation

Objective: FAM83H is one of the major pathogenic genes of amelogenesis imperfecta (AI). Previous studies focused on the abnormal enamel development and mineralization caused by the mutations in FAM83H. Here we aimed to observe other effects of FAM83H mutations on tooth eruption besides AI through clinical case analysis. Methods: Published AI cases with FAM83H mutations were searched through PubMed database, and the characteristics of tooth eruption of each cases were counted and analyzed. The literature search range was from January 1, 2008 to February 28, 2023, using the keywords FAM83H and amelogenesis imperfecta. The included literature must provide the detailed radiographic imaging or dental eruption information of AI patients, as well as FAM83H gene mutation information. The basic clinical information, tooth phenotypes, and mutations of all the enrolled cases were collected and analyzed in order to find the characteristics of abnormal tooth eruption. Results: Among 45 papers about FAM83H related to AI, twenty meeting the inclusion criteria were selected, involving 50 AI patients carrying FAM83H mutations who had radiographic image data or the detailed description of tooth eruption. A total of 34 abnormal erupted teeth were from 12 patients (12/50, 24%), among which 85% (29/34) had clear eruption path without any eruption obstructions, either embedded (25/34, 74%) or partially erupted (4/34, 12%). Tooth position analysis found that abnormal eruption of canines and second molars accounted for the highest proportion, accounting for 38% (13/34) respectively. Conclusions: The mutations in FAM83H may lead to amelogenesis imperfecta as well as abnormal tooth eruption at specific tooth positions.

Overview of Radiological Studies on Visualization of Gubernaculum Tracts of Permanent Teeth

The eruption pathway from the dental follicle to the gingiva for permanent teeth is known as the gubernaculum tract (GT), a physiologic structure thought to play a role in tooth eruption. Cone beam computed tomography and multi-detector computed tomography have recently been used to visualize the GT, with the results indicating that this structure might be related to the normal eruption of teeth. By contrast, curved and/or constricted GTs may lead to abnormal tooth eruption. In addition, complex odontomas have been reported from within the GT or dental sac of unerupted permanent teeth. If an odontoma occurs within the GT, the tooth will not erupt normally. Moreover, the imaging characteristics of the GT from the top of the odontogenic mass to the alveolar crest are extremely useful for making a differential pathological diagnosis and for differentiating between odontogenic and non-odontogenic masses. Therefore, radiological studies on the GT have been attracting increasing attention. Given this background, the present review aims to clarify the imaging characteristics and review recent studies on the GT considering the importance of the research.

Detection of the gubernacular canal and its attachment to the dental follicle may indicate an abnormal eruption status.

To evaluate and compare the detection of gubernacular canals (GC) and their characteristics in normal and abnormal tooth eruption. Patients with unerupted teeth were classified according to sex and age. Each tooth was classified according to dental group, eruption status, formation status, angulation, and GC detection. The opening of the GC in the alveolar crest and the attachment sites in relation to the dental follicle were assessed. Data were analyzed by the chi-square and Kruskal-Wallis tests, with a significance level of 5%. Cone-beam computed tomography scans of 159 patients were evaluated. The final sample (N = 598) consisted of 423 teeth with normal eruption, 140 impacted teeth, and 35 teeth with delayed eruption. The overall detection rate of GC was 90.6%. These rates were 94.1%, 87.1%, and 62.9% for normal eruption, impacted teeth, and delayed eruption, respectively. GC detection rates were higher in the early stages of tooth formation in normal tooth eruption and in impacted teeth. The rate of GC detection was even lower in delayed teeth when they were angulated. Unusual attachment sites of the GC to the dental follicle were associated with abnormal eruption status. The results of the present study suggest that GC characteristics may indicate an abnormal eruption status.

MANAGEMENT OF REGIONAL ODONTODYSPLASIA: 10-YEAR-FOLLOW-UP CASE REPORT AND LITERATURE REVIEW

The aim of this paper was to review the literature and present a case of regional odontodysplasia with details of clinical and radiographic features,thereby facilitating management of this rare anomaly. A 6-year-old girl was referred to our department with chief complaint of missing or unerupted permanent maxillary left central, lateral and canine teeth. At the affected area, the gingiva was enlarged, fibrous, and tense. Radiographic examination shows abnormally formed teeth with short roots. After 3 year follow up with temporary prosthetic rehabilitation, periodontal surgery was applied.Following forced eruption and levelling, abnormal tooth eruption and root development were observed in these three teeth. After root canal treatment with ProRoot MTA, an intracanal fiber post and the access cavity was restored with composite resin and zirconia ceramic crown. The choice of the best treatment option for ROD depends on the time of diagnosis, present/existing symptoms,functional and esthetic needs,and available treatment modalities.

Third Molar Eruption Mechanisms and Patterns

Third molars are highly variable in their presence and form. This report focuses on a horizontally impacted third molar and analyzes the potential etiology of this situation. Upon a clinical and radiographic examination, it was noted that the patient had four third molars present. The patient’s third molars began erupting around the age of 19. Currently, they are asymptomatic with incipient caries on the occlusal surfaces. While three of the third molars erupted in a normal orientation, one of the third molars (mandibular left) erupted in an orientation that would be classified as horizontal and/or mesio-angular. No treatment has been undertaken at the moment, however surgical extraction can be recommended with the prognosis being very good. For the clinician that has to treat dental complications that arise from abnormal tooth eruption, as seen in numerous genetic and acquired disorders, knowledge about the basic molecular mechanisms involved may become extremely important.

Primary failure of eruption and other eruption disorders—Considerations for management by the orthodontist and oral surgeon

Tooth eruption is a highly variable process, and the disorders that stem from a defective eruption process are often difficult to diagnose. The eruption process can range from normally timed and sequenced events to one characterized by eruption delays or a primary failure of eruption (PFE, OMIM #125350)—with partially or completely unerupted teeth in the absence of a mechanical obstruction. Our understanding of the molecular basis of tooth eruption was drastically strengthened when one gene, parathyroid hormone receptor 1 ( PTH1R ), was found to be causative for familial cases of PFE. Although PFE is a relatively rare condition, knowledge of a biological mechanism underlying the development of PFE illuminates: (1) the influence of genetics on orthodontic tooth movement in general; (2) the differential diagnosis of clinical eruption disorders; and (3) the correlation of a biologic basis with the clinical management of eruption failure. In this article, we consider the best clinical management of eruption disorders from the standpoint of what is known from a biological perspective about normal tooth eruption and therefore eruption disorders. Specifically, how the diagnosis influences the clinical management of eruption disorders using biologic versus clinical factors is considered. These advances in our understanding of normal and abnormal tooth eruption now allow for a systematic clinical diagnostic regime that may include a surgical approach or simply the elimination of treatment with a continuous archwire.

Pycnodysostosis with craniosynostosis

Pycnodysostosis (OMIM 265800) is an uncommon hereditary disorder characterized by osteosclerosis of the skeleton, short stature, and bone fragility. The syndrome was first described by Maroteaux and Lamy (1962). Facial dysmorphology, hypoplasia of the mandible,dysplasia of the skull, bones with delayed closure of the cranial sutures, clavicular dysplasia, acroosteolysis or partial aplasia of the terminal phalanges, and abnormal tooth eruption have also been reported (Gelb et al., 1995). An autosomal recessive mode of inheritance has been also suggested and the locus of the disease was initially mapped to human chromosome 1q21 by genetic linkage (Bernard et al., 1980). Since then, several mutations on unrelated patients and consanguineous families have been identified in the cathepsin K gene (CTSK), affecting osteoclast function.Only two previous reports have demonstrated the presence of craniosynostosis in patients with pycnodysostosis(Fleming et al., 2007; Osimani et al., 2010). The purpose of this case report is to describe the craniofacial and dental features of a 12-year-old boy with pycnodysostosisand an uncommon association with craniosynosotosis.

The Etiology of Eruption Disorders—Further Evidence of a “Genetic Paradigm”

The clinical spectrum of tooth eruption disorders includes both syndromic and non-syndromic problems ranging from delayed eruption to a complete failure of eruption. A defect in the differential apposition/resorption mechanism in alveolar bone can cause conditions such as tooth ankylosis, primary failure of eruption, failure of eruption due to inadequate arch length and canine impaction. As our knowledge of the molecular events underlying normal tooth eruption has increased, so too has our understanding of clinical eruption disorders. The recent finding that one gene, parathyroid hormone receptor 1 (PTH1R), is causative for familial cases of primary failure of eruption (PFE) suggests that other disturbances in tooth eruption may have a genetic etiology. In this report, we evaluated the current terminology (ankylosis, PFE, secondary retention, etc.) used to describe non-syndromic eruption disorders, in light of this genetic discovery. We observed that some individuals previously diagnosed with ankylosis were subsequently found to have alterations in the PTH1R gene, indicating the initial misdiagnosis of ankylosis and the necessary re-classification of PFE. We further investigated the relationship of the PTH1R gene, using a network pathway analysis, to determine its connectivity to previously identified genes that are critical to normal tooth eruption. We found that PTH1R acts in a pathway with genes such as PTHrP that have been shown to be important in bone remodeling, hence eruption, in a rat model. Thus, recent advances in our understanding of normal and abnormal tooth eruption should allow us in the future to develop a clinical nomenclature system based more on the molecular genetic cause of the eruption failures versus the clinical appearance of the various eruption disorders.

Abnormal Tooth Eruption in a Cat

Abnormal Tooth Eruption in a Cat

Downregulation of matrix metalloproteinases in hyperplastic dental follicles results in abnormal tooth eruption

In this study, we compared the gene expression profiles of non-syndromic hyperplastic dental follicle (HDF) fibroblasts and normal dental follicle (NDF) fibroblasts using cDNA microarrays, quantitative PCR, and immunohistochemical staining. Microarray analysis showed that several collagens genes were upregulated in the HDFos, including collagen types I, IV, VIII, and XI and TIMP-1, -3, and -4 (fold ratio > 2.0). In contrast, the expression of MMP-1, -3, -10, and -16 together with IL-8 was more than two fold downregulated. The differential expression of the genes encoding alkaline phosphatase, MMP-1, -3, -8, and IL-8 was confirmed by quantitative RT-PCR, while that of 24 HDFs and 18 NDFs was confirmed by immunohistochemical analysis. However, HDFs showed stronger expression of MMP-3 than NDFs (P < 0.001). Collectively, these results indicate that defective regulation of MMPs mediating connective tissue remodeling may be responsible for abnormal tooth eruption.

PDGF BB and bFGF stimulate DNA synthesis and upregulate CSF-1 and MCP-1 gene expression in dental follicle cells

CSF-1 and MCP-1, released by dental follicle cells, stimulate the influx of monocytes into the follicle sac and enhance the formation of osteoclasts that, in turn, resorb alveolar bone for the eruption pathway. PDGF and bFGF, released by cells adjacent to the follicle or by activated monocytes, are prime candidates that may regulate CSF-1 and MCP-1 gene expression. The present study demonstrates that PDGF and bFGF are mitogens for dental follicle cells and stimulate CSF-1 and MCP-1 mRNA, but with different time course kinetics. Peak induction of CSF-1 mRNA was observed at 6–8 h, while maximal MCP-1 induction was observed at 2 h. These findings suggest that MCP-1 is an early chemotactic signal for monocytes and that subsequent release of CSF-1 may act synergistically with MCP-1 to enhance monocyte influx. Further understanding of the molecular mechanisms by which cytokines regulate CSF-1 and MCP-1 may lead to more effective treatment regimens for disorders associated with abnormal tooth eruption.

Oral Health and hospitalization in Western Australian children

Over the past 20 years, the prevalence of dental disease in Western Australian children has diminished. The causes of this significant improvement in health are associated with better care models, water fluoridation and changes in lifestyle. In this study, the authors examine the reasons for hospitalization for oral health conditions in Western Australia for the calendar year 1995 using the Health Department of WA database. A total of 3,754 episodes of care (4,395 bed days) was recorded for dental conditions. Dental caries resulted in the fifth and sixth highest number of episodes of hospitalization in preschool (1-4 years) and primary-school age (5-12 years) children respectively. Abnormal tooth eruption resulted in the highest number of episodes of hospitalization in high-school age (13-17 years) children. From the age-stratified rates of hospitalization (per 1000), non-Aboriginal children were more than twice as likely to enter hospital for dental related conditions. The primary cause of this is the 15 times higher rate of hospitalization for high-school age non-Aboriginal children which clearly reflects the greater use of services for impacted third molars by the metropolitan non-Aboriginal community. Examination of the distribution by health service region revealed the hospitalization rate was significantly less than the state average for the Kimberley, Pilbara, Northern Goldfields and Wanneroo regions. These data reflect the paucity of oral health care available to residents of these regions, particularly the northwest, and does not reflect a diminished burden of disease. Similarly, the rate of hospitalization for Aboriginal children reflects population and service delivery differences particularly in regional and remote WA. These data highlight the need to develop new strategies in oral health care to target 'at risk' groups in the community, particularly new parents of young children. The preventive measures associated with good oral health in children are clearly aligned with those for good general health and can be integrated into existing health messages.

Delayed eruption of permanent teeth in hyperimmunoglobulinemia E recurrent infection syndrome.

To determine the incidence of abnormal tooth eruption in patients with hyperimmunoglobulinemia E (hyper-IgE) syndrome. This study evaluated 34 individuals with hyper-IgE syndrome (age range, 2-40 years). A comprehensive dental history and a head and neck evaluation were performed on all patients. Dental age was assessed in patients younger than 17 years by 2 methods: (1) clinical assessment of tooth eruption and (2) a radiographic method. Relationships between the chronologic age, dental developmental age, and age at tooth eruption were determined. Other oral or dental anomalies were recorded. Of patients older than 7 years, 75% reported problems with permanent tooth eruption, as evidenced by retained primary teeth or the need for elective extractions of primary teeth to allow eruption of permanent teeth. None of the patients experienced problems with eruption of primary teeth. Eruption of the first and second permanent molars also occurred on time. Dental maturity scores were established for 14 patients 17 years of age or younger. In each case, the difference between chronologic age and the estimated dental developmental age was less than 12 months; however, we found a significant discrepancy between the chronologic age and the mean age of tooth eruption in 80% of these patients when using a particular set of standardized values. Persistence of Hertwig's epithelial root sheath was observed on histologic examination. Chronic multifocal oral candidiasis was a consistent feature in patients with hyper-IgE recurrent infection syndrome. Other oral anomalies were also noted. We confirmed that a disorder of tooth eruption is part of the hyper-IgE syndrome. This problem occurs because of delayed primary tooth exfoliation rather than a developmental delay in the formation of the permanent dentition. The persistence of Hertwig's epithelial root sheath is unusual and may be associated with the lack of resorption of the primary teeth. Dentists should be aware of this feature of hyper-IgE syndrome because timely intervention will allow normal eruption to occur.