Root resorptions induced by genetic disorders: A systematic review.

OBJECTIVES: Root resorption in permanent teeth is a common pathological process that often follows dental trauma or orthodontic treatment. More rarely, root resorption is a feature of genetic disorders and can help with diagnosis. Thus, the present review aims to determine which genetic disorders could induce pathological root resorptions and thus which mutated genes could be associated with them. METHODS: We conducted a systematic review following the PRISMA guidelines. Articles describing root resorptions in patients with genetic disorders were included from PubMed, Embase, Web of Science, and Google Scholar. We synthesized the genetic disorder, the type, severity, and extent of the resorptions, as well as the other systemic and oral symptoms and histological features. RESULTS: The synthetic analysis included 25 studies among 937 identified records. We analyzed 21 case reports, three case series, and one cohort study. Overall, we highlighted 14 different pathologies with described root resorptions. Depending on the pathology, the sites of resorption, their extent, and their severity showed differences. CONCLUSION: With 14 genetic pathologies suspected to induce root resorptions, our findings are significant and enrich a previous classification. Among them, three metabolic disorders, three calcium-phosphorus metabolism disorders, and osteolysis disorders were identified.

[The tooth: A marker of developmental abnormalities]. / La dent : un marqueur d'anomalies génétiques du développement.

Tooth formation results from specific epithelial-mesenchymal interactions, which summarize a number of developmental processes. Tooth anomalies may thus reflect subclinical diseases of the kidney, bone and more broadly of the mineral metabolism, skin or nervous system. Odontogenesis starts from the 3rd week of intrauterine life by the odontogenic orientation of epithelial cells by a first PITX2 signal. The second phase is the acquisition of the number, shape, and position of teeth. It depends on multiple transcription and growth factors (BMP, FGF, SHH, WNT). These ecto-mesenchymal interactions guide cell migration, proliferation, apoptosis and differentiation ending in the formation of the specific dental mineralized tissues. Thus, any alteration will have consequences on the tooth structure or shape. Resulting manifestations will have to be considered in the patient phenotype and the multidisciplinary care, but also may contribute to identify the altered genetic circuity.

Title: La dent : un marqueur d'anomalies génétiques du développement. Abstract: L'odontogenèse résulte d'évènements reflétant de multiples processus impliqués dans le développement : crêtes neurales, interactions épithélio-mésenchymateuses, minéralisation. Les anomalies dentaires sont donc d'excellents marqueurs de l'impact de mutations de gènes qui affectent différents systèmes biologiques, tels que le métabolisme minéral, l'os, le rein, la peau ou le système nerveux. Dans cette revue, nous présentons de façon synthétique les gènes impliqués dans plusieurs maladies rares au travers de défauts des dents caractéristiques, de nombre, de forme et de structure.

Oro-dental phenotyping and report of three families with RELT-associated amelogenesis imperfecta.

Amelogenesis imperfecta (AI) is a group of rare genetic conditions characterized by quantitative and/or qualitative tooth enamel alterations. AI can manifest as an isolated trait or as part of a syndrome. Recently, five biallelic disease-causing variants in the RELT gene were identified in 7 families with autosomal recessive amelogenesis imperfecta (ARAI). RELT encodes an orphan receptor in the tumor necrosis factor (TNFR) superfamily expressed during tooth development, with unknown function. Here, we report one Brazilian and two French families with ARAI and a distinctive hypomineralized phenotype with hypoplastic enamel, post-eruptive enamel loss, and occlusal attrition. Using Next Generation Sequencing (NGS), four novel RELT variants were identified (c.120+1G>A, p.(?); c.120+1G>T, p.(?); c.193T>C, p.(Cys65Arg) and c.1260_1263dup, p.(Arg422Glyfs*5)). Our findings extend the knowledge of ARAI dental phenotypes and expand the disease-causing variants spectrum of the RELT gene.

Replacement of missing lateral incisors for patients with cleft lip and palate: A decision-making tree based on a systematic review of the literature.

STATEMENT OF PROBLEM: Cleft lip and palate are the most frequent congenital anomalies of the face and are often linked with lateral incisor agenesis. The therapeutic decision on whether and how to replace the lateral incisors is not straightforward, and a decision-making tree is needed. PURPOSE: The purpose of this systematic review was to evaluate the available literature reporting on treatments for the replacement of missing lateral incisors in cleft areas. By analyzing the success and survival rates of these treatments, a decision-making tree was developed. MATERIAL AND METHODS: The literature search was performed on the PubMed (MEDLINE), Web of Science, Cochrane, EMBASE, Dentistry of Oral and Science Source, and Google Scholar databases and was based on the question: Which treatment for patients with lateral incisor agenesis and cleft lip and palate has a good success rate? RESULTS: Twenty-six articles were included in this systematic review. A meta-analysis was performed on 14 articles (20 case series, 6 case controls). The estimated overall 5-year survival rates were 96.4% for implant-supported prostheses. CONCLUSIONS: Different treatment options are available, depending on the clinical situation. If the patient meets the conditions for implant placement, this treatment remains a preferred solution. If the prosthetic space is reduced, orthodontic space closure and composite resin restorations are possible. When these options are not possible, a resin-bonded fixed partial denture is the preferred option. If the teeth adjacent to the edentulous area require extensive restorations, a fixed partial denture may be a suitable alternative.

Reduced bone dimension in patients affected by oligodontia: A retrospective study on maxillary and mandibular CBCT.

AIM: Oligodontia (OD) is a rare developmental condition characterized by the absence of six or more teeth. Dental implant placement may be challenging due to anatomical factors. This study aims to evaluate the alveolar bone dimensions in OD patients compared with controls. MATERIALS AND METHODS: On maxillary and mandibular cone-beam computed tomography (CBCT), bone height and width were measured at every tooth and edentulous site. The distance to the inferior alveolar nerve was also measured. Fifty-three OD patients (40 maxillary and 32 mandibular CBCT) and 82 controls (51 maxillary and 31 mandibular CBCT) were compared using mixed models. RESULTS: Compared with those in OD patients, maxillary permanent teeth and edentulous sites showed significantly higher mean height in control patients (incisive-canine site height: +2.12 mm; edentulous incisive-canine site height: +4.46 mm [p > .001]). For the mandibular permanent teeth, mean height was higher in controls than in OD patients at the incisive-canine (+3.82 mm [p > .001]) and premolar areas (+2.06 mm [p > .001]). Only edentulous incisive-canine sites were significantly different between controls and OD patients (mean: +0.52 mm [p > .001]). Changes in alveolar nerve position were observed in case of molar agenesis. CONCLUSION: Maxillary and mandibular bone dimensions are reduced in OD patients compared with controls both in sites with permanent teeth and in edentulous areas.

The dental triage method at Rothschild Hospital during the first lockdown due to the COVID-19 pandemic.

OBJECTIVE: This study aims to (1) assess the efficacy of a face-to-face emergency protocol in children and adults and (2) measure the efficacies of prediagnosis at the triage level and clinical diagnosis at the emergency department level during the COVID-19 pandemic. METHODS: A triage protocol was applied for patients at the entry of the Rothschild Hospital (AP-HP) between March 18th and May 11th, 2020. First, patients underwent a triage based on self-reported symptoms. If their condition was deemed urgent, they were oriented toward dental professionals, who performed an intraoral examination leading to a clinical diagnosis. Triage and diagnoses were categorized into four emergency groups: infectious, prosthetic, traumatic, and others. The agreement between triage and clinical diagnosis was tested (χ2 test). Positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity for each diagnostic category were assessed to evaluate the performance and efficacy of the triage. RESULTS: Out of 1562 dental visits, 1064 were included in this analysis. The most frequently reported symptoms by children at triage were pain (31.5%) and trauma (22%). Adults mainly complained of abscesses (45.1%) and pulpitis (20.5%). The most frequent clinical diagnoses were abscesses (29.2%) and pulpitis (20.5%) among children and adults, respectively. Tooth extraction was the most frequent treatment modality. Systemic antibiotics were prescribed for 49.2% of patients. Regardless of the age class, the PPV was high for groups 1 to 3, ranging from 78.9% to 100%. The NPV was high in all groups, ranging from 68.8% to 99.1%. CONCLUSION: This study demonstrates that the triage implanted during the first COVID-19 lockdown was effective and is an appropriate tool for the referral of adults and children before clinical examination.

Oral lesions of viral, bacterial, and fungal diseases in children: A decision tree.

Oral mucosal lesions are common in the pediatric population and, apart from traumatic and tumoral etiologies, they can be symptoms of viral, bacterial, fungal or parasitic diseases. Yet, pediatricians and pediatric dentists find it challenging to reach a diagnosis and provide appropriate care when facing lesions of the masticatory or lining mucosa, of the hard or soft palate, of the tongue or salivary glands. Here, we propose a decision tree for the diagnosis of the most frequent viral, bacterial, and fungal diseases starting from their oral lesions in children. By first focusing on describing the elementary lesion itself before its localization and characteristics, it aims to guide the practitioner toward the diagnosis and any necessary complementary exams. To generate this tool, we conducted a literature review of the childhood viral, bacterial, fungal and parasitic diseases with oral mucosal symptoms. For each of the 42 reported diagnoses-20 viral, 9 bacterial, 5 fungal, and 8 parasitic-we collected the infection mechanism and agent(s), the oral lesions and their description, the associated systemic signs and the incidence/prevalence. In fine, our decision tree indexes the 28 diseases for which epidemiological data was available, mainly in Europe and the United States.

Oral Phenotype of Singleton-Merten Syndrome: A Systematic Review Illustrated With a Case Report.

Background: Singleton-Merten syndrome type 1 (SGMRT1) is a rare autosomal dominant disorder caused by IFIH1 variations with blood vessel calcifications, teeth anomalies, and bone defects. Aim: We aimed to summarize the oral findings in SGMRT1 through a systematic review of the literature and to describe the phenotype of a 10-year-old patient with SGMRT1 diagnosis. Results: A total of 20 patients were described in the literature, in nine articles. Eight IFIH1 mutations were described in 11 families. Delayed eruption, short roots, and premature loss of permanent teeth were the most described features (100%). Impacted teeth (89%) and carious lesions (67%) were also described. Our patient, a 10-year-old male with Singleton-Merten syndrome, presented numerous carious lesions, severe teeth malposition, especially in the anterior arch, and an oral hygiene deficiency with a 100% plaque index. The panoramic X-ray did not show any dental agenesis but revealed very short roots and a decrease in the jaw alveolar bone height. The whole-genome sequencing analysis revealed a heterozygous de novo variant in IFIH1 (NM_022168.4) c.2465G > A (p.Arg822Gln). Conclusion: Confused descriptions of oral features occurred in the literature between congenital findings and "acquired" pathology, especially carious lesions. The dental phenotype of these patients encompasses eruption anomalies (delayed eruption and impacted teeth) and lack of root edification, leading to premature loss of permanent teeth, and it may contribute to the diagnosis. An early diagnosis is essential to prevent teeth loss and to improve the quality of life of these patients. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42022300025].

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

METHODOLOGY: 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. 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.

Lack of FAM20A, Ectopic Gingival Mineralization and Chondro/Osteogenic Modifications in Enamel Renal Syndrome.

Enamel renal syndrome (ERS) is a rare recessive disorder caused by loss-of-function mutations in FAM20A (family with sequence similarity 20 member A, OMIM #611062). Enamel renal syndrome is characterized by amelogenesis imperfecta, delayed or failed tooth eruption, intrapulpal calcifications, gingival overgrowth and nephrocalcinosis. Although gingival overgrowth has consistently been associated with heterotopic calcifications the pathogenesis, structure and interactions of the mineral deposits with the surrounding connective tissue are largely unknown. We here report a novel FAM20A mutation in exon 1 (c.358C > T) introducing a premature stop codon (p.Gln120*) and resulting in a complete loss of FAM20A. In addition to the typical oral findings and nephrocalcinosis, ectopic calcified nodules were also seen in the cervical and thoracic vertebrae regions. Histopathologic analysis of the gingiva showed an enlarged papillary layer associated with aberrant angiogenesis and a lamina propria displaying significant changes in its extracellular matrix composition, including disruption of the collagen I fiber network. Ectopic calcifications were found throughout the connective gingival tissue. Immunomorphological and ultrastructural analyses indicated that the calcification process was associated with epithelial degeneration and transformation of the gingival fibroblasts to chondro/osteoblastic-like cells. Mutant gingival fibroblasts cultures were prone to calcify and abnormally expressed osteoblastic markers such as RUNX2 or PERIOSTIN. Our findings expand the previously reported phenotypes and highlight some aspects of ERS pathogenesis.

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

Abstract 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.

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.

Translation and cross-cultural validation of the French version of the Sleep-Related Breathing Disorder scale of the Pediatric Sleep Questionnaire.

BACKGROUND: Sleep-disordered breathing (SDB), including obstructive sleep apnea syndrome, is often underestimated because it requires a burdensome test (ie, polysomnography) to ensure diagnosis. To improve polysomnography referral, it is of utmost importance to validate efficient alternative screening tools. This study aimed to provide a translation and a cross-cultural validation of the Pediatric Sleep Questionnaire (PSQ) into French to obtain an easy-to-use and reliable screening tool. The psychometric properties of the French version were also determined. METHODS: The process of cross-cultural adaptation was carried out following these steps: forward-backward translation, evaluation by an expert committee, and pretesting of the pre-final version. Reliability of the French-PSQ version was assessed by Cronbach's alpha coefficients and Spearman's correlation on a convenient sample of 201 children (aged between 2 and 17 years). Construct validity was determined by factor analysis of principal components. RESULTS: Internal consistency was within an adequate range for all subscales: 0.711 for snoring, 0.559 for sleepiness, 0.682 for behavioral problems, and 0.776 for the whole questionnaire. Spearman's correlation analysis comparing questionnaires administered two weeks apart showed good correlation coefficients for all subscales (snoring: 0.642, sleepiness: 0.846, behavioral problems: 0.780, and entire SRBD scale: 0.835). Factor analysis performed to assess the structure of the French-SRBD scale confirmed the same four factors described in the original questionnaire ("breathing," "behavior," "sleepiness," and "other"). CONCLUSION: The French version of the PSQ has been successfully cross-culturally adapted and showed good psychometric properties, suggesting that it is useful as a tool to screen sleep-disordered breathing in French-speaking children.

Parental-Caregivers Perceptions Questionnaire (P-CPQ): translation and evaluation of psychometric properties of the French version of the questionnaire.

BACKGROUND: The Parental-Caregivers Perceptions Questionnaire (P-CPQ) is a measure of parental/caregivers' perceptions of the impact of children's oral health on quality of life. The aim of the study was evaluate the psychometric properties of the French version of the P-CPQ. METHOD: The original P-CPQ was developed in English language and has 31 items divided into four sub-scales. This cross-sectional study used the translation-back translation method. The translated questionnaire was pretested on 14 parents-caregivers to obtain the final French version. The psychometric properties were tested on 142 parents/caregivers of three clinical groups of children from 8 to 10 years old without dental/facial anomalies (presumed healthy), with oral-facial clefts and with oral-dental anomalies linked to a rare disease other than cleft, approached in the waiting room of the Centre of the Hospital Rothschild in Paris, France, where the children attended treatment. Internal consistency was assessed by Cronbach's alpha and test-retest reliability by Intra-class Correlation Coefficient (ICC). Construct validity was measured by correlations between the total scores and the global ratings of oral health and overall wellbeing, and tested using exploratory factor analysis (EFA) and the factorial structure was evaluated by the partial confirmatory factor analysis (PCFA). Discriminant validity was determined using Kruskall-Wallis test. RESULTS: The mean (standard deviation) P-CPQ score was 18.73(18.79). Internal consistency was confirmed by a Cronbach alpha of 0.85. The test-retest reliability revealed that the responses to items were satisfactorily stable (ICC = 0.88). Construct validity was demonstrated by significant correlation coefficients between the total scale and the global ratings (r = 0.54 and 0.46; p < 0.001). Factor analysis with Principal Component Analysis extracted seven factors explaining 65.23% cumulative variance. Goodness-of-fit indices for partial confirmatory factor analysis were satisfactory for the 7-factors model of the French-PCPQ version. There were statistically significant differences between clinical groups regarding the total scale, thus demonstrating discriminant validity (p < 0.001). CONCLUSION: This French P-CPQ version showed reliability and validity comparable to the previous versions. However, the cross-cultural structure of the subscales should be further evaluated.

SLC10A7 mutations cause a skeletal dysplasia with amelogenesis imperfecta mediated by GAG biosynthesis defects.

Skeletal dysplasia with multiple dislocations are severe disorders characterized by dislocations of large joints and short stature. The majority of them have been linked to pathogenic variants in genes encoding glycosyltransferases, sulfotransferases or epimerases required for glycosaminoglycan synthesis. Using exome sequencing, we identify homozygous mutations in SLC10A7 in six individuals with skeletal dysplasia with multiple dislocations and amelogenesis imperfecta. SLC10A7 encodes a 10-transmembrane-domain transporter located at the plasma membrane. Functional studies in vitro demonstrate that SLC10A7 mutations reduce SLC10A7 protein expression. We generate a Slc10a7-/- mouse model, which displays shortened long bones, growth plate disorganization and tooth enamel anomalies, recapitulating the human phenotype. Furthermore, we identify decreased heparan sulfate levels in Slc10a7-/- mouse cartilage and patient fibroblasts. Finally, we find an abnormal N-glycoprotein electrophoretic profile in patient blood samples. Together, our findings support the involvement of SLC10A7 in glycosaminoglycan synthesis and specifically in skeletal development.

Amelogenesis imperfecta: therapeutic strategy from primary to permanent dentition across case reports.

BACKGROUND: Hereditary enamel defect diseases are regrouped under the name "Amelogenesis Imperfecta" (AIH). Both dentitions are affected. Clinical expression is heterogeneous and varies between patients. Mutations responsible for this multigene disease may alter various genes and the inheritance can be either autosomal dominant or recessive, or X-linked. Until now, no therapeutic consensus has emerged for this rare disease. CASE PRESENTATION: The purpose of this article was to report treatments of AIH patients from childhood to early adulthood. Treatment of three patients of 3, 8 16 years old are described. Each therapeutic option was discussed according to patients' age and type of enamel alteration. Paediatric crowns and resin based bonding must be preferred in primary teeth. In permanent teeth, non-invasive or minimally invasive dentistry should be the first choice in order to follow a therapeutic gradient from the less invasive options to prosthodontic treatments. CONCLUSION: Functional and aesthetic issues require patients to be treated; this clinical care should be provided as early as possible to enable a harmonious growth of the maxillofacial complex and to prevent pain.

Translation and validation of the French version of the Child Perceptions Questionnaire for children aged from 8 to 10 years old (CPQ 8-10).

BACKGROUND: The Child Perceptions Questionnaire (CPQ) belongs to a set of questionnaires measuring Child Oral Health Quality of Life (COHQOL). The CPQ is used to collect the perceptions of children on the impact of oral diseases on their quality of life. This cross-sectional study was aimed to translate the CPQ8-10 into French language and evaluate its psychometric properties. METHODS: The translation process complied with international recommendations. The final French version was tested on children aged 8-10 years old attending consultations in a Parisian public hospital and divided into three groups: children with oral-facial clefts, children with dental anomalies linked to a rare disease other than clefts and children presumed to be healthy and without anomalies. The internal consistency relating to the reliability of CPQ8-10 was evaluated by Cronbach's alpha. The intra-class correlation was used to measure reproducibility at the test-retest level. Construct validity was evaluated by Spearman's correlation and tested using factor analysis. The discriminant validity was assessed using Kruskall Wallis test. Criterion validity was calculated using Spearman's correlation. RESULTS: One hundred seventy-six children participated in this study. During the translation process, minor changes were made. The French version showed good reliability with a Cronbach's alpha of 0.81 for the total scale. The ICC of the test-retest was excellent (=0.90) demonstrating good reproducibility. The construct validity was acceptable with a statistically significant correlation between the scores of the French-CPQ8-10 and the evaluation of oral health (r = 0. 381 and p < 0.001) and its impact on oral health quality of life (r = 0.363 and p < 0.001). The loading weights obtained in the Exploratory Factor Analysis showed that this model revealed seven factors with eigenvalue greater than 1, explaining the 63,89% of the cumulative variance. The differences observed between the scores of the study groups revealed good discriminant validity. Criterion validity was supported by significant association between CPQ scores and pain. CONCLUSION: The French-CPQ8-10 is reliable and valid for use with the children of this age group.

Prosthetic Rehabilitation of a Patient with Rare and Severe Enamel Renal Syndrome.

Dental rehabilitation of acute cases of enamel renal syndrome is challenging due to the absence of clinical reports. In the present case history report, examination of an 18-year-old patient revealed a complete lack of permanent teeth, as well as irregular and swollen bone and gingival morphology. Radiographs showed multiple impacted teeth in both arches. Creating a 1.5- to 2-cm interarch space was necessary for setting complete dentures. The ideal occlusal plane was chosen by combining two techniques (cephalometric radiograph and modification of the mandibular occlusal rim according to anatomical guidelines). Extraction of impacted teeth and recontouring of the alveolar process were performed simultaneously. The mandibular denture was connected through Locator abutments to two symphyseal implants. This pioneering clinical report will provide guidance to practitioners in the surgical intervention of patients with FAM20A (family with sequence similarities 20 A) gene mutations.

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.

Management of rare diseases of the Head, Neck and Teeth: results of a French population-based prospective 8-year study.

BACKGROUND: In the last ten years, national rare disease networks have been established in France, including national centres of expertise and regional ones, with storage of patient data in a bioinformatics tool. The aim was to contribute to the development and evaluation of health strategies to improve the management of patients with rare diseases. The objective of this study has been to provide the first national-level data concerning rare diseases of the head, neck and teeth and to assess the balance between demand and supply of care in France. METHODS: Centres of expertise for rare diseases record a minimum data set on their clinical cases, using a list of rare Head, Neck and Teeth diseases established in 2006. The present analysis focuses on 2008 to 2015 data based on the Orphanet nomenclature. Each rare disease RD "case" was defined by status "affected" and by the degree of diagnostic certainty, encoded as: confirmed, probable or non-classifiable. Analysed parameters, presented with their 95% confidence intervals using a Poisson model, were the following: time and age at diagnosis, proportions of crude and standardized RD prevalence by age, gender and geographical site. The criteria studied were the proportions of patients in Paris Region and the "included cases geography", in which these proportions were projected onto the other French Regions, adjusting for local populations. RESULTS: In Paris Region, estimated prevalence of these diseases was 5.58 per 10,000 inhabitants (95% CI 4.3-7.1). At December 31st 2015, 11,342 patients were referenced in total in France, of whom 7294 were in Paris Region. More than 580 individual clinical entities (ORPHA code) were identified with their respective frequencies. Most abnormalities were diagnosed antenatally. Nearly 80% of patients recorded come to Paris hospitals to obtain either diagnosis, care or follow up. We observed that the rarer the disease, the more patients were referred to Paris hospitals. CONCLUSIONS: A health network covering a range of aspects of the rare diseases problematic from diagnostics to research has been developed in France. Despite this, there is still a noticeable imbalance between health care supply and demand in this area.