Displasia dentinaria tipo I: Manejo clínico y estudio histológico a propósito de dos casos

La displasia dentinaria tipo I (DD-I) corresponde a una alteración dentinaria de heterogeneidad genética y penetrancia completa, en donde se presenta un defecto en el desarrollo de las raíces de los dientes tanto temporales como definitivos. Clínicamente se observan dientes con extrema movilidad junto con antecedentes de exfoliación prematura o espontánea. Los defectos estructurales de los tejidos dentarios, tales como DD-I; implican un desafío ya que son pocos los casos documentados en la literatura que hablan de esta condición. Además implican un tratamiento multidisciplinario y altamente invasivo. El objetivo de este artículo es presentar dos casos de DD-I, enfatizando en su tratamiento y características histopatológicas.

Dentin Dysplasia Type I (DD-I) consists of a pathological dentinary alteration with genetic heterogeneity that results in a defectuous development of dental roots both in primary and secondary dentition. Clinically we can appreciate teeth with extreme pathological mobility and premature or spontaneous exfoliation. Alterations within normal dental structure, such as DD-I imply a challenge for the common practitioner, because of the scarce number of case reports with in the scientific literature regarding this condition and also, because of the need for a highly invasive and multidisciplinary approach they require. The aim of this article is to present two DD-I cases, emphasizing on their treatment and histopathological features.

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.

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.

Mutation in SSUH2 Causes Autosomal-Dominant Dentin Dysplasia Type I.

Dentin dysplasia type I (DDI) is an autosomal-dominant genetic disorder resulting from dentin defects. The molecular basis of DDI remains unclear. DDI exhibits unique characteristics with phenotypes featuring obliteration of pulp chambers and diminutive root, thus providing a useful model for understanding the genetics of tooth formation. Using a large Chinese family with 14 DDI patients, we mapped the gene locus responsible for DDI to 3p26.1-3p24.3 and further identified a missense mutation, c.353C>A (p.P118Q) in the SSUH2 gene on 3p26.1, which co-segregated with DDI. We showed that SSUH2 (p.P118Q) perturbed the structure and significantly reduced levels of mutant (MT) protein and mRNA compared with wild-type SSUH2. Furthermore, MT P141Q knock-in mice (+/- and -/-) had a unique partial obliteration of the pulp cavity and upregulation or downregulation of six major genes involved in odontogenesis: Dspp, Dmp1, Runx2, Pax9, Bmp2, and Dlx2. The phenotype of missing teeth was determined in zebrafish with morpholino gene knockdowns and rescued by injection of normal human mRNA. Taken together, our observations demonstrate that SSUH2 disrupts dental formation and that this novel gene, together with other odontogenesis genes, is involved in tooth development.

Malformations of the tooth root in humans.

The most common root malformations in humans arise from either developmental disorders of the root alone or disorders of radicular development as part of a general tooth dysplasia. The aim of this review is to relate the characteristics of these root malformations to potentially disrupted processes involved in radicular morphogenesis. Radicular morphogenesis proceeds under the control of Hertwig's epithelial root sheath (HERS) which determines the number, length, and shape of the root, induces the formation of radicular dentin, and participates in the development of root cementum. Formation of HERS at the transition from crown to root development appears to be very insensitive to adverse effects, with the result that rootless teeth are extremely rare. In contrast, shortened roots as a consequence of impaired or prematurely halted apical growth of HERS constitute the most prevalent radicular dysplasia which occurs due to trauma and unknown reasons as well as in association with dentin disorders. While odontoblast differentiation inevitably stops when growth of HERS is arrested, it seems to be unaffected even in cases of severe dentin dysplasias such as regional odontodysplasia and dentin dysplasia type I. As a result radicular dentin formation is at least initiated and progresses for a limited time. The only condition affecting cementogenesis is hypophosphatasia which disrupts the formation of acellular cementum through an inhibition of mineralization. A process particularly susceptible to adverse effects appears to be the formation of the furcation in multirooted teeth. Impairment or disruption of this process entails taurodontism, single-rooted posterior teeth, and misshapen furcations. Thus, even though many characteristics of human root malformations can be related to disorders of specific processes involved in radicular morphogenesis, precise inferences as to the pathogenesis of these dysplasias are hampered by the still limited knowledge on root formation.

Dentin dysplasia type I - A rare entity.

Dentin dysplasia is a rare disturbance of dentin formation characterized by normal enamel but atypical dentin formation with abnormal pupal morphology. The teeth appear clinically normal in morphologic appearance and color. The teeth characteristically exhibit extreme mobility and are commonly exfoliated prematurely. Radiograph shows obliteration of all pulp chambers, short, blunted and malformed or absent roots with periapical radiolucencies involving apparently intact tooth. This case is reported here because of its rarity along with the description of various clinical, radiological and histological features.