Gingival inflammation, enamel defects, and tooth sensitivity in children with amelogenesis imperfecta: a case-control study

Gingival conditions and tooth sensitivity of young patients with amelogenesis imperfecta lack in depth studies. This case-control study aimed to compare (1) the gingival inflammation, the presence of enamel defects, and tooth sensitivity in young patients with and without amelogenesis imperfecta and (2) to investigate if any difference exists between subtypes of amelogenesis imperfecta. Methodology: We compared forty-two participants with amelogenesis imperfecta with forty-two controls matched for age, gender, and the number of examined sites. Based on interview, clinical examination, and intraoral photography, we collected data on periodontal conditions, enamel defects and the presence of tooth sensitivity. Comparison tests were performed to investigate if any difference existed between cases and controls; and among cases, between the different subtypes of amelogenesis imperfecta. We performed a post-hoc analysis for any significant difference observed. Results: We observed more gingival inflammation, enamel defects and tooth sensitivity among cases (all p<0.05). Participants with hypocalcified amelogenesis imperfecta had more gingival inflammation, enamel defects, and tooth sensitivity than patients with the hypoplastic and hypomature subtypes (all p<0.05). After adjustment for dental plaque, gingival inflammation was associated with the presence of amelogenesis imperfecta (OR (95%CI) = 1.14 (1.05; 1.24). p<0.01). Conclusion: Gingival inflammation, enamel defect and tooth sensitivity are more frequently observed among young patients with amelogenesis imperfecta, and more specifically among children with the hypocalcified subtype

FAM20A Gene Mutation: Amelogenesis or Ectopic Mineralization?

Background and objective:FAM20A gene mutations result in enamel renal syndrome (ERS) associated with amelogenesis imperfecta (AI), nephrocalcinosis, gingival fibromatosis, and impaired tooth eruption. FAM20A would control the phosphorylation of enamel peptides and thus enamel mineralization. Here, we characterized the structure and chemical composition of unerupted tooth enamel from ERS patients and healthy subjects.Methods: Tooth sections were analyzed by Scanning Electron Microscopy (SEM), Energy Dispersive Spectroscopy (EDS), X-Ray Diffraction (XRD), and X-Ray Fluorescence (XRF).Results: SEM revealed that prisms were restricted to the inner-most enamel zones. The bulk of the mineralized matter covering the crown was formed by layers with varying electron-densities organized into lamellae and micronodules. Tissue porosity progressively increased at the periphery, ending with loose and unfused nanonodules also observed in the adjoining soft tissues. Thus, the enamel layer covering the dentin in all ERS patients (except a limited layer of enamel at the dentino-enamel junction) displayed an ultrastructural globular pattern similar to one observed in ectopic mineralization of soft tissue, notably in the gingiva of Fam20a knockout mice. XRD analysis confirmed the existence of alterations in crystallinity and composition (vs. sound enamel). XRF identified lower levels of calcium and phosphorus in ERS enamel. Finally, EDS confirmed the reduced amount of calcium in ERS enamel, which appeared similar to dentin.Conclusion: This study suggests that, after an initial normal start to amelogenesis, the bulk of the tissue covering coronal dentin would be formed by different mechanisms based on nano- to micro-nodule aggregation. This evocated ectopic mineralization process is known to intervene in several soft tissues in FAM20A gene mutant

Elements of morphology: Standard terminology for the teeth and classifying genetic dental disorders

Dental anomalies occur frequently in a number of genetic disorders and act as major signs in diagnosing these disorders. We present definitions of the most common dental signs and propose a classification usable as a diagnostic tool by dentists, clinical geneticists, and other health care providers. The definitions are part of the series Elements of Morphology and have been established after careful discussions within an international group of experienced dentists and geneticists. The classification system was elaborated in the French collaborative network 'TÊTECOU' and the affiliated O-Rares reference/competence centers. The classification includes isolated and syndromic disorders with oral and dental anomalies, to which causative genes and main extraoral signs and symptoms are added. A systematic literature analysis yielded 408 entities of which a causal gene has been identified in 79%. We classified dental disorders in eight groups: dental agenesis, supernumerary teeth, dental size and/or shape, enamel, dentin, dental eruption, periodontal and gingival, and tumor-like anomalies. We aim the classification to act as a shared reference for clinical and epidemiological studies. We welcome critical evaluations of the definitions and classification and will regularly update the classification for newly recognized conditions

Tracking Endogenous Amelogenin and Ameloblastin In Vivo

Research on enamel matrix proteins (EMPs) is centered on understanding their role in enamel biomineralization and their bioactivity for tissue engineering. While therapeutic application of EMPs has been widely documented, their expression and biological function in non-enamel tissues is unclear. Our first aim was to screen for amelogenin (AMELX) and ameloblastin (AMBN) gene expression in mandibular bones and soft tissues isolated from adult mice (15 weeks old). Using RT-PCR, we showed mRNA expression of AMELX and AMBN in mandibular alveolar and basal bones and, at low levels, in several soft tissues; eyes and ovaries were RNA-positive for AMELX and eyes, tongues and testicles for AMBN. Moreover, in mandibular tissues AMELX and AMBN mRNA levels varied according to two parameters: 1) ontogenic stage (decreasing with age), and 2) tissue-type (e.g. higher level in dental epithelial cells and alveolar bone when compared to basal bone and dental mesenchymal cells in 1 week old mice). In situ hybridization and immunohistodetection were performed in mandibular tissues using AMELX KO mice as controls. We identified AMELX-producing (RNA-positive) cells lining the adjacent alveolar bone and AMBN and AMELX proteins in the microenvironment surrounding EMPs-producing cells. Western blotting of proteins extracted by non-dissociative means revealed that AMELX and AMBN are not exclusive to mineralized matrix; they are present to some degree in a solubilized state in mandibular bone and presumably have some capacity to diffuse. Our data support the notion that AMELX and AMBN may function as growth factor-like molecules solubilized in the aqueous microenvironment. In jaws, they might play some role in bone physiology through autocrine/paracrine pathways, particularly during development and stress-induced remodeling

A targeted next-generation sequencing assay for the molecular diagnosis of genetic disorders with orodental involvement.

BACKGROUND: Orodental diseases include several clinically and genetically heterogeneous disorders that can present in isolation or as part of a genetic syndrome. Due to the vast number of genes implicated in these disorders, establishing a molecular diagnosis can be challenging. We aimed to develop a targeted next-generation sequencing (NGS) assay to diagnose mutations and potentially identify novel genes mutated in this group of disorders. METHODS: We designed an NGS gene panel that targets 585 known and candidate genes in orodental disease. We screened a cohort of 101 unrelated patients without a molecular diagnosis referred to the Reference Centre for Oro-Dental Manifestations of Rare Diseases, Strasbourg, France, for a variety of orodental disorders including isolated and syndromic amelogenesis imperfecta (AI), isolated and syndromic selective tooth agenesis (STHAG), isolated and syndromic dentinogenesis imperfecta, isolated dentin dysplasia, otodental dysplasia and primary failure of tooth eruption. RESULTS: We discovered 21 novel pathogenic variants and identified the causative mutation in 39 unrelated patients in known genes (overall diagnostic rate: 39%). Among the largest subcohorts of patients with isolated AI (50 unrelated patients) and isolated STHAG (21 unrelated patients), we had a definitive diagnosis in 14 (27%) and 15 cases (71%), respectively. Surprisingly, COL17A1 mutations accounted for the majority of autosomal-dominant AI cases. CONCLUSIONS: We have developed a novel targeted NGS assay for the efficient molecular diagnosis of a wide variety of orodental diseases. Furthermore, our panel will contribute to better understanding the contribution of these genes to orodental disease. TRIAL REGISTRATION NUMBERS: NCT01746121 and NCT02397824.journal articleresearch support, non-u.s. gov't2016 Feb2015 10 26importe

Nephrocalcinosis (enamel renal syndrome) caused by autosomal recessive FAM20A mutations

Calcium homeostasis requires regulated cellular and interstitial systems interacting to modulate the activity and movement of this ion. Disruption of these systems in the kidney results in nephrocalcinosis and nephrolithiasis, important medical problems whose pathogenesis is incompletely understood

Ostéopétrose d'origine génétique (signes cliniques et manifestations cranio-faciales)

L ostéopétrose est une maladie héréditaire rare comprenant des formes cliniquement et génétiquement hétérogènes avec comme caractéristique radiologique commune une densité osseuse augmentée. Malgré cet os en excès , le squelette est fragile et les os se fracturent facilement suite à des traumatismes mineurs. L ostéopétrose est due à un déséquilibre de la balance entre la résorption et la formation osseuse en faveur de la résorption osseuse. Deux phénomènes l expliquent : un dysfonctionnement des ostéoclastes suite à une diminution de leur différenciation ou une altération de leurs fonctions. Différentes étiologies sont retrouvées: génétiques, acquises, médicamenteuses. L étiologie génétique reste la plus fréquente. Sept gènes sont retrouvés mutés chez l homme : TCIRG1, CLCN7, OSTM1, CA2, LPR5, TNFSF11, PLEKHI\41. Ils codent pour des protéines impliquées dans la formation et la fonction des ostéoclastes. Il existe différentes formes d ostéopétrose dont l évolution et la sévérité sont variables allant du décès in utéro à des formes restant totalement asymptomatiques. Les manifestations cliniques sont diverses : insuffisance de l hématopoïèse médullaire, de la croissance et du remodelage du squelette, une diminution de la taille des foramen osseux crâniens, une diminution de la vascularisation osseuse et des troubles immunologiques prédisposant à l infection. Au niveau dentaire, on retrouve des anomalies de la morphogenèse et des retards d éruption. Des ostéomyélites des maxillaires sont des complications rares associées à l ostéopétrose mais d une particulière gravité.PARIS7-Odontologie (751062104) / SudocSudocFranceF

Patients dysmorphiques : une relecture des signes cliniques mineurs vers un diagnostic

Le chirurgien-dentiste peut se sentir démuni face à une maladie rare : (a) difficultés diagnostiques, (b) complexité thérapeutique, (c) questionnement des parents, sont les trois obstacles majeurs que nous avons à résoudre pour mener à bien notre thérapeutique. Même si la génétique a fait d’énormes progrès ces dernières années, c’est avant tout les connaissances cliniques qui nous orientent vers le diagnostic. Certains syndromes présentent des signes très discrets qui seuls peuvent paraître anodins mais qui, pris ensemble, définissent une entité pathologique. Savoir où trouver ces signes et les reconnaître est donc le premier défi à relever

Dysmorphic Patients: A Review of Minor Clinical Signs Leading to a Diagnosis

The dental surgeon can feel inadequate when confronted with a rare disease: (a) difficult diagnosis, (b) therapeutic complexity, (c) and questioning by the parents, are three major obstacles that we have to overcome in order to carry out our therapy. Even if the field of genetics has made major advances during the last few years, it is clinical knowledge, above all, that leads us to a diagnosis. Certain syndromes present with very subtle signs which alone can appear trivial but which, taken together, defines a pathological entity. To know or to discover these signs and to recognize them is therefore the first challenge

Le syndrome de Fraser (de la clinique à la génétique)

Le syndrome de Fraser ou syndrome de cryptophtalmie-syndactylie-agénésie rénale est une maladie rare. Ce large syndrome polymalformatif est caractérisé principalement par une cryptophtahnie, une syndactylie, une agénésie rénale et des malformations génitales. Au niveau crânio-facial, on retrouve des anomalies du développement squelettique (palais ogival, malocclusions), des fentes labio-palatines et des anomalies dentaires (microdonties, agénésies, retard d éruption). Son diagnostic est essentiellement basé sur des critères phénotypiques cliniques. Chez l homme, 2 gènes sont retrouvés mutés : FRASI et EREM2. Ces gènes codent pour des protéines de la matrice extracellulaire localisées dans les membranes basales. Elles forment, avec FREM1, un complexe trimérique jouant un rôle dans les interactions derme-épiderme et dans l organogenèse durant le développement. Quatre modèles animaux de souris mutantes blebbing , présentant des mutations pour les gènes Faisi, Fremi. Frein2 et Gripi, reproduisent les altérations observées chez l homme. L expression et la fonction de ces protéines ont été analysées in vivo mais leurs implications dans le développement dentaire et crânio-facial restent méconnues. L objectif de cette thèse est d essayer d identifier l expression de ces gènes dans la sphère cranio-faciale par le technique de la RT-PCR.PARIS7-Odontologie (751062104) / SudocSudocFranceF