Hereditary dentin defects with systemic diseases.

OBJECTIVE: This review aimed to summarize recent progress on syndromic dentin defects, promoting a better understanding of systemic diseases with dentin malformations, the molecules involved, and related mechanisms. SUBJECTS AND METHODS: References on genetic diseases with dentin malformations were obtained from various sources, including PubMed, OMIM, NCBI, and other websites. The clinical phenotypes and genetic backgrounds of these diseases were then summarized, analyzed, and compared. RESULTS: Over 10 systemic diseases, including osteogenesis imperfecta, hypophosphatemic rickets, vitamin D-dependent rickets, familial tumoral calcinosis, Ehlers-Danlos syndrome, Schimke immuno-osseous dysplasia, hypophosphatasia, Elsahy-Waters syndrome, Singleton-Merten syndrome, odontochondrodysplasia, and microcephalic osteodysplastic primordial dwarfism type II were examined. Most of these are bone disorders, and their pathogenic genes may regulate both dentin and bone development, involving extracellular matrix, cell differentiation, and metabolism of calcium, phosphorus, and vitamin D. The phenotypes of these syndromic dentin defects various with the involved genes, part of them are similar to dentinogenesis imperfecta or dentin dysplasia, while others only present one or two types of dentin abnormalities such as discoloration, irregular enlarged or obliterated pulp and canal, or root malformation. CONCLUSION: Some specific dentin defects associated with systemic diseases may serve as important phenotypes for dentists to diagnose. Furthermore, mechanistic studies on syndromic dentin defects may provide valuable insights into isolated dentin defects and general dentin development or mineralization.

Identification of DSPP novel variants and phenotype analysis in dentinogenesis dysplasia Shields type II patients.

OBJECTIVES: To investigate the genetic causes and teeth characteristics of dentin dysplasia Shields type II(DD-II) in three Chinese families. MATERIALS AND METHODS: Data from three Chinese families affected with DD-II were collected. Whole-exome sequencing (WES) and whole-genome sequencing (WGS) were conducted to screen for variations, and Sanger sequencing was used to verify mutation sites. The physical and chemical characteristics of the affected teeth including tooth structure, hardness, mineral content, and ultrastructure were investigated. RESULTS: A novel frameshift deletion mutation c.1871_1874del(p.Ser624fs) in DSPP was found in families A and B, while no pathogenic mutation was found in family C. The affected teeth's pulp cavities were obliterated, and the root canals were smaller than normal teeth and irregularly distributed comprising a network. The patients' teeth also had reduced dentin hardness and highly irregular dentinal tubules. The Mg content of the teeth was significantly lower than that of the controls, but the Na content was obviously higher than that of the controls. CONCLUSIONS: A novel frameshift deletion mutation, c.1871_1874del (p.Ser624fs), in the DPP region of the DSPP gene causes DD-II. The DD-II teeth demonstrated compromised mechanical properties and changed ultrastructure, suggesting an impaired function of DPP. Our findings expand the mutational spectrum of the DSPP gene and strengthen the understanding of clinical phenotypes related to the frameshift deletion in the DPP region of the DSPP gene. CLINICAL RELEVANCE: A DSPP mutation can alter the characteristics of the affected teeth, including tooth structure, hardness, mineral content, and ultrastructure.

A novel DSPP frameshift mutation causing dentin dysplasia type 2 and disease management strategies.

The present study aims to investigate the mutation in a Chinese family with dentin dysplasia type II (DD-II) and to summarize mutation hotspots, clinical manifestations, and disease management strategies. Phenotype analysis, clinical intervention, mutation screening, and cosegregation analysis within the enrolled family were performed. A summary of the reported mutations in the dentin phosphoprotein (DPP) region of dentin sialophosphoprotein (DSPP) was analyzed. Pathogenicity prediction analysis of the physical properties and function of DSPP variants was performed by bioinformatic processing. Clinical management strategies are discussed. A novel pathogenic mutation (c.2035delA) in the DPP region of DSPP was identified, which was cosegregated in the family. The immature permanent teeth of patients with DD-II presented with X-shaped root canal phenotypes. Most of the identified mutations for DD-II were clustered in the DPP region between nucleotides 1686-2134. Points of differential diagnosis, clinical interventions, and management strategies are proposed. This study revealed a novel DSPP frameshift mutation and presented new clinical features of DD-II. The locus involving nucleotides 1686-2134 of DSPP may represent a mutational hotspot for the disease. Appropriate management of DD-II at different stages is important to avoid the development of secondary dental lesions.

Displasia dentinária tipo i: relato de caso / Dentin dysplasia type i: case report / Displasia dentinaria tipo i: informe de un caso

A displasia dentinária tipo I é um distúrbio hereditário autossômico dominante raro, associada a uma malformação da dentina radicular, que pode causar a perda espontânea dos dentes. Clinicamente, os dentes apresentam aspectos de normalidade, no entanto, radiograficamente, podem ser observadas raízes curtas e mal formadas. O objetivo desse trabalho foi relatar o diagnóstico de uma paciente portadora de displasia dentinária tipo I. Paciente, M.G.S, sexo feminino, 34 anos, compareceu a Clínica Odontológica da UFC ­ Sobral com intuito de fazer uma nova prótese parcial removível. Ao realizar o exame clínico, contatou-se que a paciente apresentava uma boa higiene oral, porém observou-se mobilidade e dor nos dentes 12, 13, 23, 32 e 33, além do relato de perda precoce de outros elementos dentários devido a mobilidade. Foram realizadas radiografias periapicais, onde foi observado pela primeira vez o aspecto encurtado de todas as raízes dentárias. O encurtamento das raízes foi novamente observado na radiografia panorâmica e na tomografia computadorizada solicitadas a paciente. Após o estudo do caso, a paciente foi diagnosticada com Displasia Dentinária tipo I. A paciente foi reabilitada com prótese protocolo superior e inferior. Conclui-se que a Displasia Dentinária tipo I é uma condição rara e que afeta a dentina radicular de dentes decíduos e permanentes. O tratamento da DDI é difícil e requer abordagem multidisciplinar, devendo devolver a autoestima, além de favorecer a função mastigatória e a estética.

Dentin dysplasia dentin type I is a rare autosomal dominant hereditary disorder associated with a root dentin malformation that can cause spontaneous tooth loss. Clinically, the teeth present normal aspects; however, radiographically, short and malformed roots can be observed. The aim of this paper was to report the diagnosis of a patient with dentin dysplasia type I. Patient, M.G.S, female, 34 years, attended the Dental Clinic of UFC - Sobral in order to make a new partial denture. During clinical examination it was found that the patient had good oral hygiene, but there was mobility and pain in teeth 12, 13, 23, 32 and 33, besides the report of early loss of other teeth due to mobility. Periapical radiographs were taken, where the shortened appearance of all dental roots was first observed. The shortening of the roots was again observed in the panoramic radiograph and CT scan requested from the patient. After the case study, the patient was diagnosed with Dentin Dysplasia type I. The patient was rehabilitated with upper and lower protocol prosthesis. It is concluded that Dentin Dysplasia type I is a rare condition and affects the root dentin of deciduous and permanent teeth. The treatment of DDI is difficult and requires a multidisciplinary approach, and should restore self-esteem, in addition to favoring masticatory function and aesthetics.

La displasia dentinaria tipo I es un trastorno hereditario autosómico dominante poco frecuente asociado a una malformación de la dentina radicular que puede causar la pérdida espontánea de dientes. Clínicamente, los dientes presentan aspectos normales; sin embargo, radiográficamente pueden observarse raíces cortas y malformadas. El objetivo de este estudio fue informar sobre el diagnóstico de un paciente con displasia dentinaria tipo I. Paciente, M.G.S, sexo femenino, 34 años, acudió a la Clínica Odontológica de UFC - Sobral con el objetivo de realizar una nueva prótesis parcial removible. En el examen clínico, se constató que la paciente tenía buena higiene bucal, pero se observó movilidad y dolor en los dientes 12, 13, 23, 32 y 33, y el informe de pérdida precoz de otros elementos dentales debido a la movilidad. Se tomaron radiografías periapicales y por primera vez se observó el aspecto acortado de todas las raíces dentales. El acortamiento de las raíces se observó de nuevo en la radiografía panorámica y el TAC solicitados a la paciente. Tras el estudio del caso, la paciente fue diagnosticada de displasia dentinaria tipo I. La paciente fue rehabilitada con prótesis de protocolo superior e inferior. Se concluye que la Displasia Dentinaria tipo I es una enfermedad rara y afecta a la dentina radicular de los dientes deciduos y permanentes. El tratamiento de la DDI es difícil y requiere un abordaje multidisciplinar, debiendo restaurar la autoestima, además de favorecer la función masticatoria y la estética.

A Review of Dentinogenesis Imperfecta and Primary Dentin Disorders in Dogs.

This review describes the clinical, radiographic and histologic characteristics of dentinogenesis imperfecta diagnosed in two unrelated young dogs without evidence of concurrent osteogenesis imperfecta. The dentition was noted to have generalized coronal discoloration ranging from grey-blue to golden brown. Clinical pulp exposure, coronal wear and fractures were observed as was radiographic evidence of endodontic disease, thin dentin walls or dystrophic obliteration of the pulp canal. The enamel was severely affected by attrition and abrasion despite histologically normal areas; loss was most likely due to poor adherence or support by the underlying abnormal dentin. Histologically, permanent and deciduous teeth examined showed thin, amorphous dentin without organized dentin tubules and odontoblasts had dysplastic cell morphology. Primary dentin disorders, including dentinogenesis imperfecta and dentin dysplasia, have been extensively studied and genetically characterized in humans but infrequently reported in dogs. Treatment in human patients is aimed at early recognition and multi-disciplinary intervention to restore and maintain normal occlusion, aesthetics, mastication and speech. Treatment in both humans and canine patients is discussed as is the documented genetic heritability of primary dentin disorders in humans.

A Case of X-Linked Hypophosphatemic Rickets with Dentin Dysplasia in Mandibular Third Molars.

X-linked hypophosphatemic rickets (XLH) is a disease characterized by impaired bone mineralization, and its dental features include gingival abscesses and large pulp spaces due to dentin dysplasia. A 20-year-old woman with XLH was referred to oral surgery for extraction of mandibular third molars. She was diagnosed with XLH at approximately 1 year of age and was treated thereafter. There was no history of gingival abscesses, and panoramic radiographic and computed tomographic examinations revealed no evidence of dentin dysplasia. However, histopathological examination of the extracted teeth showed dentin dysplasia, including interglobular dentin. In this XLH patient, dentin dysplasia was revealed histologically even though no obvious abnormality was found on visual and radiographic examinations. These findings suggest that in patients with XLH, oral management must take dentin dysplasia of the permanent teeth into consideration even if the patient's general condition is well controlled with conventional therapy.

The Modified Shields Classification and 12 Families with Defined DSPP Mutations.

Mutations in Dentin Sialophosphoprotein (DSPP) are known to cause, in order of increasing severity, dentin dysplasia type-II (DD-II), dentinogenesis imperfecta type-II (DGI-II), and dentinogenesis imperfecta type-III (DGI-III). DSPP mutations fall into two groups: a 5'-group that affects protein targeting and a 3'-group that shifts translation into the −1 reading frame. Using whole-exome sequence (WES) analyses and Single Molecule Real-Time (SMRT) sequencing, we identified disease-causing DSPP mutations in 12 families. Three of the mutations are novel: c.53T>C/p.(Val18Ala); c.3461delG/p.(Ser1154Metfs*160); and c.3700delA/p.(Ser1234Alafs*80). We propose genetic analysis start with WES analysis of proband DNA to identify mutations in COL1A1 and COL1A2 causing dominant forms of osteogenesis imperfecta, 5'-DSPP mutations, and 3'-DSPP frameshifts near the margins of the DSPP repeat region, and SMRT sequencing when the disease-causing mutation is not identified. After reviewing the literature and incorporating new information showing distinct differences in the cell pathology observed between knockin mice with 5'-Dspp or 3'-Dspp mutations, we propose a modified Shields Classification based upon the causative mutation rather than phenotypic severity such that patients identified with 5'-DSPP defects be diagnosed as DGI-III, while those with 3'-DSPP defects be diagnosed as DGI-II.

Micro-CT study on isolated teeth with hereditary dentin defects.

OBJECTIVES: To construct the three-dimensional structure of the isolated teeth of patients with dentinogenesis imperfecta type Ⅱ (DGI-Ⅱ) and dentin dysplasia type Ⅰ (DD-Ⅰ) by using Micro-CT and explore internal structure and hard tissue mineralization density. METHODS: The three-dimensional structures of the third molars collected from patients with DGI-Ⅱ and DD-Ⅰ and healthy individuals of the same age were reconstructed by using Micro-CT (Mimics 17.0). The internal structures of the affected teeth along the sagittal and transverse planes were observed. The grayscale values of the enamel, crown dentin, and root dentin were calculated. Then, the mineralization densities of the different parts of the teeth of the three groups were analyzed. RESULTS: The detailed three-dimensional models of the mandibular third molars with hereditary dentin defects were successfully constructed. The models contained the models of the enamel cap, dentin core, and pulp cavity. Sagittal and transverse section scans revealed that in patients with DGI-Ⅱ, the pulp cavity was incompletely calcified and the root canal was narrow, whereas in those with DD-Ⅰ, the pulp cavity and root canal were obliterated and the root of the tooth was absent. The analysis of the grayscale values showed that compared with those in the healthy group, the grayscale values of the enamel, crown dentin, and root dentin were lower in the DGI-Ⅱ and DD-Ⅰ groups (P<0.01). No significant differences in the grayscale values of the enamel and crown dentin were found between the DGI-Ⅱ and DD-Ⅰ groups (P>0.05), whereas the grayscale value of the root dentin showed statistically significant differences between the two groups (P<0.01). CONCLUSIONS: The application of Micro-CT provided a simple and accurate method for the three-dimensional structure reconstruction and quantitative analysis of the mineralization density of isolated teeth with hereditary dentin defects. Although the dentin mineralization density of DGI-Ⅱ and DD-Ⅰ teeth decreased, the decrement shown by DD-Ⅰ teeth was more significant than that shown by DGI-Ⅱ teeth. The pulp cavity had abnormal calcifications, and the root canal was narrow or even occluded.

Generalized Dentin Dysplasia in a Four-Year-old dog.

Dentin dysplasia is an autosomal-dominant genetic abnormality that occurs in humans and results in diffuse radiographic dental abnormalities and variable tooth discoloration due to an underlying defect in secondary dentinogenesis. This case report presents distinctive radiographic and histopathologic dental abnormalities in a dog that are consistent with generalized dentin dysplasia. These findings are similar to but not completely analogous to any specific clinical type of dentin dysplasia in humans. Grossly, the majority of the teeth in this case were discolored and most were determined to be vital. Dentin dysplasia should be included in the list of differential diagnoses of discolored teeth and notably this form of discoloration does not necessarily indicate loss of vitality.

Orthodontic Treatment of a Patient with Dentin Dysplasia Type I and Bilateral Maxillary Canine Impaction: Case Presentation and a Family-Based Genetic Analysis.

Dentin dysplasia is a rare hereditary disorder, transmitted by autosomal dominant mode, affecting both dentin and pulp. In Type I crown morphology is normal, but root dentin organization loss leads to shorter roots. Mutations in the SSUH2, VPS4B and SMOC2 genes have been reported as responsible for this condition. Orthodontic treatment was conducted on an 11-year-old female patient presenting the disorder along with bilaterally impacted permanent maxillary canines, in close proximity to the roots of the lateral and central incisors. Treatment plan included lateral incisors extraction, surgical exposure and traction of the impacted canines. Light forces were applied from a custom-made trans-palatal arch. Comprehensive orthodontic treatment was performed using edgewise appliances. After 3 years and 2 months, group function occlusion was achieved. The canines underwent composite resin restorations. At one year post-retention, the dentition remained stable. Family-based genetic analysis did not reveal any mutations in the aforementioned genes pointing to further genetic heterogeneity of this disorder. As dental medicine becomes more sophisticated and personalized, the association between mutation type/function and orthodontic treatment response may provide useful therapeutic insights. The positive treatment response of the presented case could be attributed to a more "benign" mutation awaiting to be identified.

Endodontic treatment of dentin dysplasia type I D.

Dentin dysplasia (DD) Type I is a developmental condition affecting dentin, inherited in an autosomal-dominant pattern or occurring due to a new mutation. Whilst the crowns of DD Type I affected teeth appear clinically normal, the roots are blunt and shortened. Pulp necrosis and periapical pathoses may be seen in the absence of obvious causes. Pulp stones and calcifications are frequently encountered. Endodontic management of DD may be challenging. A case of DD Type I, sub-classification d, in which spontaneous irreversible pulpitis developed on three mandibular incisors is documented. The case was managed by conventional endodontic treatment. Knowledge of this uncommon dental condition may assist dentists to adequately diagnose and manage these cases. Extraction should not be considered the first-line treatment option when sufficient root length is available to attempt endodontic treatment. Referral for medical evaluation is recommended to rule out systemic diseases which may mimic this condition.

Guided endodontic treatment of multiple teeth with dentin dysplasia: a case report.

BACKGROUND: To report the outcome of guided endodontic treatment (GET) of a case of dentin dysplasia with pulp canal calcification (PCC) and apical periodontitis based on the use of a 3D-printed template designed by merging cone-beam computed tomography (CBCT) and surface scan data. CASE PRESENTATION: A 12-year old female with radicular dentin dysplasia type I (DD-1) presented for endodontic treatment. Radiography revealed PCC in all teeth and apical radiolucency in seven teeth (12, 15, 26, 31, 32, 36 and 46). Tooth 36 had the most acute symptoms and was thus treated first by conventional access cavity preparation and root canal detection. Despite meticulous technique, the distal and mesiolingual canals were perforated. The perforations were immediately repaired with mineral trioxide aggregate, and the decision was made to switch to guided endodontic treatment for the remaining 6 teeth. CBCT and intraoral surface scans were acquired and matched using coDiagnostix planning software (Dental Wings Inc.), the respective drill positions for root canal location were determined, and templates were virtually designed and 3D-printed. The template was positioned on the respective tooth, and a customized drill was used to penetrate the calcified part of the root canal and perform minimally invasive access cavity preparation up to the apical region. All root canals were rapidly and successfully located with the templates. At 1-year follow-up, clear signs of apical healing were present in all treated teeth. CONCLUSIONS: In patients with dentin dysplasia, conventional endodontic therapy is challenging. GET considerably facilitates the root canal treatment of teeth affected by dentin dysplasia.

[Gene mutations and disorders of dental hard tissues].

Developmental disorders of dental hard tissues are important components of non-carious diseases, which mainly include amelogenesis imperfecta and hereditary dentin disorders with various subtypes. In the absence of effective intervention, these disorders would lead to tooth sensitivity, defects of tooth structure or even loss of tooth, affecting the masticatory function and facial aesthetic configuration. At present, many dental clinicians may not have sufficient understanding of the diseases, and it is urgent to pay attention to the diseases per se and the patients affected. Based on the summary of the current research progresses, this article focuses on the clinical classification, the disease phenotype and the pathogenesis of gene mutations, in order to provide reference and help for the dental clinicians as well as the patients.

An unusual variation of radicular dentin dysplasia: A rare case report with review of literature.

Dentin dysplasia (DD) is a rare autosomal dominant disorder of dentin development, which is generally divided into two types based on the clinical and radiographic appearance of the affected dentinal tissues: Type-I (Radicular DD) and Type-II (Coronal DD). This paper reports the case of a 17-year-old female patient with both classical and atypical features of radicular DD in the permanent dentition. The present case shows clinically normal appearing crowns, localised mobility in the maxillary teeth, completely obliterated pulp chambers, widened root canals without any obliterations and the presence of multiple periapical radiolucencies. The clinical and radiographic findings observed in this present case report are different from those reported in the past literature, which suggests that the present case could be a variation of radicular DD.

A histological continuum between dentinogenesis imperfecta and dentin dysplasia: A case report with literature review.

Dentinogenesis Imperfecta and dentin dysplasia are genetic oral diseases inherited in a simple autosomal dominant mode, with high penetrance and a low mutation rate. Both of them are present with bulbous crowns, marked cervical constrictions, severe attritions, few periapical radiolucencies, and premature tooth loss. The diagnosis is based on family history, and detailed clinical examination, while genetic diagnosis may become useful in the future once sufficient disease-causing mutations have been discovered. Here, we present a case with overlapping features of both dentinogenesis imperfecta and dentin dysplasia asserting both the anomalies to be part of the same continuum of the genetic event.

Dentin dysplasia Type I: A rare case report.

Dentin dysplasia (DD) is an uncommon developmental disturbance affecting dentin, resulting in enamel with atypical dentin formation and abnormal pulpal morphology. Type I (radicular) and Type II (coronal) are the two types of DD. Type I is more common, and both types include single or multiple teeth in primary and permanent dentition. Combinations of both types have also been described in literature. Four distinct forms of Type I and one form of Type II were identified. This case report documents one such rarity of DD in an 11-year-old female with clinical and radiographical findings and management aspects.

Vacuolar protein sorting 4B regulates the proliferation and odontoblastic differentiation of human dental pulp stem cells through the Wnt-ß-catenin signalling pathway.

Our previous studies have revealed that a dominant mutation in vacuolar protein sorting 4B (VPS4B), a member of the AAA ATPase family, causes dentin dysplasia type I. The purpose of the present study was to investigate the roles of VPS4B in human dental pulp stem cells (hDPSCs) and to elucidate the underlying molecular mechanisms. In this study, we found that VPS4B was highly expressed in the dental pulp cells of the mouse molar tooth germ, and the expression of VPS4B increased significantly during the odontoblastic differentiation of hDPSCs. VPS4B downregulation inhibited the proliferation, migration, and odontoblastic differentiation of hDPSCs. Moreover, treatment with lithium chloride, an agonist of the Wnt-ß-catenin signalling pathway, partially reversed the VPS4B knockdown-driven suppression of proliferation and of odontoblastic differentiation of hDPSCs. Collectively, our findings indicate that VPS4B, via Wnt-ß-catenin signalling, acts as a regulator of the proliferation and differentiation of hDPSCs. Our results suggest potential therapeutic avenues for dentin formation and regenerative endodontics in patients with dentin dysplasia type I.

Vps4b heterozygous mice do not develop tooth defects that replicate human dentin dysplasia I.

BACKGROUND: Vacuolar protein sorting-associated protein 4B (VPS4B) is a member of the ATP enzyme AAA protein family, and is mainly involved in protein degradation and cell membrane fusion. Recently, a dominant mutation in this gene was identified in human dentin dysplasia type I (DD-I). Herein, we report the generation of Vps4b knockout (Vps4b KO) mice; however, the homozygous Vps4b KO mutation was embryonic lethal at the early stages of embryo development, and we therefore report the results of heterozygous mutant mice. RESULTS: Mice heterozygous for Vps4b did not develop tooth defects replicating human DD-I. Immunohistochemistry showed that gene KO was successful, as there was decreased expression of Vps4b in heterozygous mice; hematoxylin and eosin (H&E) staining also showed that the width of the pre-dentin zone was increased in heterozygous mice, although the arrangement of the odontoblasts was not significantly different from wild-type (WT) mice. However, H&E staining showed no obvious abnormalities in the bones of heterozygous mice. Moreover, stereomicroscopic and X-ray radiography results indicated no abnormal manifestations in teeth or bones. Furthermore, statistical analysis of the volume and density of dentin and enamel, as well as skeletal analysis, including the volume and separation of trabecular bone analyzed by micro-CT, all showed no differences between Vps4b heterozygotes and WT mice. In addition, there also were no significant differences in bone or cartilage mineralization as evaluated by Alcian blue-Alizarin red staining. CONCLUSIONS: The heterozygous Vps4b KO mice do not develop tooth defects that replicate human DD-I and this is likely to be due to differences in tooth development between the two species. Consequently, further studies are needed to determine whether mice are an appropriate animal model for human tooth diseases.

Dentin dysplasia type I.

This paper describes a rare case of genetically determined dentin dysplasia type Iin 26-year-old male patient. The paper highlights anatomical and radiologicalaspects of dental abnormalities and emphasizes the significance of the educationof both general practitioners and paediatricians as regards referring patients withdiagnosed dentin dysplasia for a multi-specialty therapy.