The spectrum of orofacial manifestations in systemic sclerosis: a challenging management.

Systemic sclerosis (SSc) is a rare multisystem connective tissue disorder characterized by the triad fibrosis, vasculopathy and immune dysregulation. This chronic disease has a significant impact on the orofacial region that is involved in more than two-thirds of the cases. SSc patients can show a wide array of oral manifestations, which are usually associated with a severe impairment of the quality of life. They often present a decreased the salivary flow and a reduced mouth opening that contribute substantially to the worsening of the oral health status. Therefore, SSc patients require specific and multidisciplinary interventions that should be initiated as early as possible. The identification of specific radiological and clinical signs at the early stage will improve the management of such patients. This study reviews the wide spectrum of orofacial manifestations associated with SSc and suggests clues for the oral management that remains challenging.

Airway Phenotypes and Nocturnal Wearing of Dentures in Elders with Sleep Apnea.

The objective of this study was to examine to what extent the anatomic characteristics of the upper airway can influence the effect of nocturnal wearing of dentures on the sleep of edentulous elders with untreated sleep apnea. This study used the data from a randomized crossover clinical trial and an exploratory approach to address its objectives. Cone beam computed tomography scans of 65 edentulous individuals (female, n = 37; male, n = 28; mean ± SD age, 74.54 ± 6.42 y) with untreated obstructive sleep apnea (OSA) were used to identify anatomic variables. Polysomnography data were collected by means of one portable overnight recording. The respiratory variable values, including apnea-hypopnea index (AHI), with and without denture worn during sleep were used to calculate the change. Statistical analyses included multiple linear regressions, cluster analysis, and binary logistic regressions. A receiver operator characteristic curve was used to illustrate the accuracy of the statistical model. The regression model explained 15.8% (R2) of AHI change. An increase in the lateral dimension of the minimum cross-sectional area was associated with a decrease in AHI, oxygen desaturation index, and respiratory arousal index changes (P ≤ 0.041). Furthermore, an increase in the length of the hypopharynx was associated with an increase in AHI and oxygen desaturation index changes (P ≤ 0.027). An increase in the lateral dimension of the minimum cross-sectional area of the upper airway was associated with a decreased likelihood of being in the group having a worsened AHI (odds ratio = 0.85; 95% CI, 0.76 to 0.95; P = 0.006). An increase in the length of the oropharynx was associated with an increased likelihood of having increased AHI (odds ratio = 1.10; 95% CI, 1.01 to 1.20; P = 0.026). The nocturnal aggravation of respiratory variables in edentulous individuals with OSA who wear dentures at night can be linked to certain anatomic characteristics of the upper airway. Replication of these findings may open novel avenues for personalized advice regarding nocturnal wearing of dentures in edentulous individuals with OSA (ClinicalTrials.gov: NCT01868295).

X-linked and autosomal recessive Hypohidrotic Ectodermal Dysplasia: genotypic-dental phenotypic findings.

Hypohidrotic ectodermal dysplasia (HED) is characterized by abnormal development of ectodermal structures and its molecular etiology corresponds to mutations of EDA-EDAR genes. The aim of this study was first to investigate the genotype and dental phenotype associated with HED and second, to explore possible correlations between dental features and molecular defects. A total of 27 patients from 24 unrelated families exhibiting clinical signs of HED (22 XLHED males, 5 autosomal recessive forms) were retrospectively included. In the sample, 25 different mutations on EDA and EDAR genes were detected; 10 were not previously described. EDA and EDAR mutations corresponded respectively to 80.0% and 20.0% of the mutations. The dental phenotype analysis revealed a mean number of primary and permanent missing teeth ranging respectively from 14.5 (4-20) to 22.5 (10-28); the majority of the patients exhibited dysmorphic teeth. Overall, no differential expression in the degree of oligodontia according to either the mutated gene, the mutated functional sub-domains, or the mutation type, could be observed. Nevertheless, the furin group exhibited severe phenotypes unobserved in the TNF group. Significant differences in the number of some primary missing teeth (incisor and canine) related to EDA-EDAR genes defects were detected for the first time between XLHED and autosomal recessive HED, suggesting differential local effects of EDA-EDAR genes during odontogenesis. The present genotypic-phenotypic findings may add to the knowledge of the consequences of the molecular dysfunction of EDA-NF-kB in odontogenesis, and could be helpful in genetic counseling to distinguish autosomal forms from other HED syndromes.

Quantification of taurodontism: interests in the early diagnosis of hypohidrotic ectodermal dysplasia.

OBJECTIVE: The aim of this study was to provide a quantification of taurodontism in Hypohidrotic Ectodermal Dysplasia (HED) and to report its occurrence in a cohort of HED patients to assess phenotypic-genotypic correlations. PATIENTS AND METHODS: Of 68 HED patients retrospectively reviewed, 16 patients aged 7-51 years were selected and compared with a control sample (n = 351). The pulp surface index of the first lower permanent molar was calculated from the panoramic radiograph of each individual, and statistical comparisons between the HED patients and the control sample were performed. RESULTS: Whatever the genetic disorder, 81.25% of the HED patients exhibited a relative enlargement (>or=1 s.d.) of the pulp. Major deviations (>5 s.d.) were respectively related to men affected by large deletion of the EDA gene or missense mutation. The autosomal recessive form was linked to a relative moderate pulp enlargement (3.44 s.d.). In NEMO forms, the increase of pulp size in men appeared to be less marked than in EDA mutations. CONCLUSION: This study provides for the first time an objective assessment of pulp enlargement in HED patients, and the various degrees of taurodontism depicted could be interesting dental phenotypic markers of HED forms.

Consequences of X-linked hypohidrotic ectodermal dysplasia for the human jaw bone.

Mutations of the Eda gene, which encodes for ectodysplasin-A1, result in X-linked hypohydrotic ectodermal dysplasia (XLHED). This pathology may lead to severe oligodontia, subsequently requiring implant therapy. Since Eda is suspected to participate in bone development, the jaw bone status was investigated in XLHED patients in order to adjust the surgical protocol. Using computed tomography, densitometric profiles and 3D reconstructions, the bone structure was analyzed and compared to that of control individuals; our results showed that the morphological changes comprised mandibular bone flattening. Craniofacial CT scans showed medullary bone hyperdensity, including in the mandibular symphysis area, where implants must be placed. These alterations in bone structure were also observed in locations where the presence/absence of teeth cannot interfere. If the changes in jaw bone morphology can be a consequence of oligodontia, the changes in bone structure seem to be tooth-independent and suggest a direct effect of the mutation on bone formation and/or remodeling.

Dento-craniofacial phenotypes and underlying molecular mechanisms in hypohidrotic ectodermal dysplasia (HED): a review.

The hypohidrotic ectodermal dysplasias (HED) belong to a large and heterogeneous nosological group of polymalfomative syndromes characterized by dystrophy or agenesis of ectodermal derivatives. Molecular etiologies of HED consist of mutations of the genes involved in the Ectodysplasin (EDA)-NF-kappaB pathway. Besides the classic ectodermal signs, craniofacial and bone manifestations are associated with the phenotypic spectrum of HED. The dental phenotype of HED consists of various degrees of oligodontia with other dental abnormalities, and these are important in the early diagnosis and identification of persons with HED. Phenotypic dental markers of heterozygous females for EDA gene mutation-moderate oligodontia, conical incisors, and delayed dental eruption-are important for individuals giving reliable genetic counseling. Some dental ageneses observed in HED are also encountered in non-syndromic oligodontia. These clinical similarities may reflect possible interactions between homeobox genes implicated in early steps of odontogenesis and the Ectodysplasin (EDA)-NF-kappaB pathway. Craniofacial dysmorphologies and bone structural anomalies are also associated with the phenotypic spectrum of persons with HED patients. The corresponding molecular mechanisms involve altered interactions between the EDA-NF-kappaB pathway and signaling molecules essential in skeletogenic neural crest cell differentiation, migration, and osteoclastic differentiation. Regarding oral treatment of persons with HED, implant-supported prostheses are used with a relatively high implant survival rate. Recently, groundbreaking experimental approaches with recombinant EDA or transgenesis of EDA-A1 were developed from the perspective of systemic treatment and appear very promising. All these clinical observations and molecular data allow for the specification of the craniofacial phenotypic spectrum in HED and provide a better understanding of the mechanisms involved in the pathogenesis of this syndrome.

Sexual dimorphism of the human mandible: demonstration by elliptical Fourier analysis.

A new quantitative approach of the mandibular sexual dimorphism, based on computer-aided image analysis and elliptical Fourier analysis of the mandibular outline in lateral view is presented. This method was applied to a series of 117 dentulous mandibles from 69 male and 48 female individuals native of Rhenish countries. Statistical discriminant analysis of the elliptical Fourier harmonics allowed the demonstration of a significant sexual dimorphism in 97.1% of males and 91.7% of females, i.e. in a higher proportion than in previous studies using classical metrical approaches. This original method opens interesting perspectives for increasing the accuracy of sex identification in current anthropological practice and in forensic procedures.