No description available.

No description available.

Purpose: The specific aim of this study is to evaluate the trends in dental health care for individuals with ectodermal dysplasia. Methods: This was a cross sectional analysis of subjects recruited through the National Foundation of Ectodermal Dysplasia (NFED). From 1997 to 2000, individuals with ectodermal dysplasia or their caregiver (if the individuals were too young to selfreport) voluntarily completed questionnaires. The questionnaire consisted of 37 items consisting of demographics, ectodermal dysplasia diagnosis, access to dental care, level of dental utilization, and type of dental services received. Descriptive statistics were used in addition to ANOVA analyses to evaluate the changing trends in oral health care for individuals with ectodermal dysplasia. Results: Preliminary results indicate: 1) individuals with ectodermal dysplasia are being diagnosed earlier than in the past, 2) physicians are primary source of the initial diagnosis of ectodermal dysplasia, 3) children with ectodermal dysplasia are receiving prostheses earlier than in the past, and 4) access to care is problematic. Conclusion: Diagnosis and recognition of treatment needs are occurring at an earlier age and that an access to dental care for individuals with ectodermal dysplasia continues to be an issue.

No description available.

Clouston hidrotic ectodermal dysplasia (BED) is an autosomal dominant skin disorder that is characterized by nail dystrophy, hair defects and palmoplantar hyperkeratosis. This condition has been described in families of various ethnic origins but is particularly common in the French Canadian population. Using linkage analysis in eight French Canadian families segregating HED, we mapped the HED gene to the pericentromeric region of chromosome 13q with a combined two-point lod score of 8.12 at zero recombination from the marker D13S175. Haplotype analysis allowed us to define D13S143 as the telomeric flanking marker for the HED candidate region. We tested five genes that map to this region, connexin 26, connexin 46, fibroblast growth factor 9, zinc-finger ZNF198 and alpha tubulin TUBA2, for involvement in HED by PCR-SSCP analysis. No mutation specific to HED was found in any of them suggesting that they most likely are not defective in this disease. / To facilitate the identification of the HED gene, we constructed a radiation hybrid (RH) map of 48 loci surrounding the HED locus on chromosome 13q. This map integrates 3 genes (TUBA2, GJbeta2 and FGF-9) and 18 ESTs with 27 markers including 19 polymorphic loci. A major inconsistency in order involving a reversed interval of six loci was found between our RH map and a YAC contig established in the region. We used Fiber-FISH and FISH on interphase nuclei to confirm our order. To refine the localization of the HED gene, we isolated eight new chromosome 13q polymorphic (CA)n markers and used seven of them along with three others in genetic analysis of a multiethnic group of 29 HED families. We demonstrated genetic homogeneity in HED in four families of French, Spanish, African and Malaysian origins and showed evidence for a strong founder effect in families of French Canadian origin. Recombination mapping placed the HED gene in a 2.4 cM region flanked by D13S1828 proximally and D13S1830 distally. Multipoint linkage and linkage disequilibrium analyses finely mapped the HED gene at 0--0.08 cM telomeric to D13S1835. These studies will greatly facilitate the physical mapping and positional cloning of the HED gene.

Ectodermal dysplasia with immunodeficiency (ED-ID) is a rare primary immunodeficiency syndrome characterized by defects in ectodermal tissues (skin, hair and sweat glands), recurrent infections, impaired response to Toll-like receptor ligands, hypogammaglobulinemia and deficient antibody production. It is caused by defective \(NF\kappa B\) signaling. The most common form of ED-ID is X-linked. It is caused by hypomorphic mutations in the \(NF\kappa B\) essential modifier gene NEMO, which is an important regulatory component in the \(NF\kappa B\) signaling pathway. We report the first case of ED-ID caused by insufficient expression of a NEMO protein of normal sequence, due to a mutation in the 5’ untranslated region of the NEMO gene. Autosomal dominant ED-ID, a rare form of ED-ID, has been reported to be caused by a heterozygous S32I mutation in the \(I \kappa B \alpha\). This mutation prevents IκBα phosphorylation and inhibits its degradation. The mutant sequesters \(NF\kappa B\) in the cytoplasm and acts as a dominant negative. We report the first ED-ID patient with a heterozygous mutation (W11X) that causes N-terminal truncation of \(I \kappa B \alpha\) and results in functional haploinsufficiency. We have constructed a knock-in mouse model of ED-ID caused by a heterozygous S32I mutation in \(I \kappa B \alpha\). The mutant mice had ED, increased mortality, complete lack of lymph nodes and Peyer’s patches, and disorganized spleens that lacked follicles, marginal zone B cells and follicular dendritic cells. T cell proliferation and cytokine production was normal in vitro, but in vivo contact hypersensitivity was severely impaired, B cell function in vitro and specific antibody response to antigens were severely reduced. All immune defects, except those that affected B cell function, were absent in \(I \kappa B \alpha\) S32I mutant \(Rag2^{-/- }\) bone marrow chimeras, indicating that defects in non-lymphiod cells play a major role in the immunodeficiency of patients with ED-ID due to mutations in \(I \kappa B \alpha\). This has important clinical implications, as bone marrow transplant may not be able to correct immune function in such patients. The lessons learned in these chapters may be applicable to other mutations that impair \(NF\kappa B\) signaling and have important implications for the treatment of patients who carry these mutations.

Diss. (sammanfattning) Umeå : Umeå universitet, 2010. / Härtill 4 uppsatser.

Displasia ectodérmica hipoidrótica é uma doença genética rara, clinicamente caracterizada por alterações envolvendo os dentes, pele e suas estruturas anexas. Manifestações orais comuns incluem anadontia ou oligodontia, dentes conóides e xerostomia. Poucos relatos associam displasia ectodérmica e redução do fluxo salivar. O objetivo desse estudo é analisar possíveis alterações nas glândulas salivares de dez portadores de displasia ectodérmica que fazem acompanhamento no Departamento de Dermatologia Pediátrica da Universidade de São Paulo. Ultrassonografia foi realizada em dez casos em infantes portadores de displasia ectodérmica hipoidrótica nas suas glândulas salivares parótida e submandibular. Três apresentaram alterações na glândula parótida e/ou submandibular. Aplasia ou hipoplasia das glândulas salivares maiores é associada a casos de displasia ectodérmica e sugere-se acompanhamento rotineiro das glândulas salivares maiores usando ultrassonografia para prevenção de alterações decorrentes da hiposalivação na cavidade oral. / Background- Hypohidrotic ectodermal dysplasia is a rare genetic disease, clinically characterized by defects involving skin and their adnexal structures, as well as oral structures such as teeth, and occasionally salivary glands. These latter manifestations include anodontia or hypodontia, conical teeth and xerostomia. Objective- To analyze possible alterations in major salivary glands of ten patients with ectodermal dysplasia, using image exam. Methods- Ultrasonography was performed in ten pediatric cases of hypohidrotic ectodermal dysplasia to investigate the status of parotid and submandibular salivary gland. Results- Three patients presented aplasia/hypoplasia of at least one gland examined. The other 7 patients did not present any alterations in parotid and submandibular glands. Limitations- Although ultrasonography exam is adequate to investigate the presence and status of major salivary glands, other important glands such as sublingual and minor mucous salivary glands are not well-visualized using this technique. Conclusions- Aplasia or hypoplasia of the major salivary gland is strongly related to ectodermal dysplasia and we suggest routine evaluation of the major salivary gland using ultrasound to monitor and manage the possible impact of xerostomia in oral health.

Displasia ectodérmica hipoidrótica é uma doença genética rara, clinicamente caracterizada por alterações envolvendo os dentes, pele e suas estruturas anexas. Manifestações orais comuns incluem anadontia ou oligodontia, dentes conóides e xerostomia. Poucos relatos associam displasia ectodérmica e redução do fluxo salivar. O objetivo desse estudo é analisar possíveis alterações nas glândulas salivares de dez portadores de displasia ectodérmica que fazem acompanhamento no Departamento de Dermatologia Pediátrica da Universidade de São Paulo. Ultrassonografia foi realizada em dez casos em infantes portadores de displasia ectodérmica hipoidrótica nas suas glândulas salivares parótida e submandibular. Três apresentaram alterações na glândula parótida e/ou submandibular. Aplasia ou hipoplasia das glândulas salivares maiores é associada a casos de displasia ectodérmica e sugere-se acompanhamento rotineiro das glândulas salivares maiores usando ultrassonografia para prevenção de alterações decorrentes da hiposalivação na cavidade oral. / Background- Hypohidrotic ectodermal dysplasia is a rare genetic disease, clinically characterized by defects involving skin and their adnexal structures, as well as oral structures such as teeth, and occasionally salivary glands. These latter manifestations include anodontia or hypodontia, conical teeth and xerostomia. Objective- To analyze possible alterations in major salivary glands of ten patients with ectodermal dysplasia, using image exam. Methods- Ultrasonography was performed in ten pediatric cases of hypohidrotic ectodermal dysplasia to investigate the status of parotid and submandibular salivary gland. Results- Three patients presented aplasia/hypoplasia of at least one gland examined. The other 7 patients did not present any alterations in parotid and submandibular glands. Limitations- Although ultrasonography exam is adequate to investigate the presence and status of major salivary glands, other important glands such as sublingual and minor mucous salivary glands are not well-visualized using this technique. Conclusions- Aplasia or hypoplasia of the major salivary gland is strongly related to ectodermal dysplasia and we suggest routine evaluation of the major salivary gland using ultrasound to monitor and manage the possible impact of xerostomia in oral health.

The general aim of this thesis was to broaden our knowledge of the signs and symptoms, genetics, and outcomes of dental implant treatment in individuals with oligodontia or ectodermal dysplasia. Article I is a population-based study in three Swedish counties of 162 individuals with oligodontia, which was a prevalence of 0.09%. The intent was to explore ways for dentists to assess symptoms from other ectodermal structures than teeth through a clinical interview and chair-side analyses. Thirty per cent had low salivary secretion rates while only 11% with no known syndrome reported symptoms from hair, nails, or sweat glands. These are, together with teeth, the ectodermal structures on which it is proposed that a clinical diagnosis of ectodermal dysplasia (ED) be based. Article II screened 93 probands with oligodontia for mutations in six genes known to cause oligodontia and hypohidrotic ED. Sequence alterations predicted to be damaging or potentially damaging were revealed in the AXIN2, MSX1, PAX9, and EDARADD genes in 14 (15%) of the probands. All mutations but one were novel. For the first time, EDARADD mutations were shown to cause isolated oligodontia. No individual who had reported ectodermal symptoms from hair, nails, or sweat glands had a mutation. Article III assessed orofacial function in individuals with different types of EDs using the Nordic Orofacial Test-Screening (NOT-S) protocol. Individuals with ED scored significantly higher in orofacial dysfunction than a healthy reference sample, especially in the Chewing and swallowing, Dryness of the mouth, and Speech domains. Article IV surveyed treatment outcome of dental implants in Swedish children up to age 16 years. In a 20-year period, only 26 patients were treated, 5 of whom had hypohidrotic ED and anodontia of the mandible. Individuals with ED had 64% failed implants compared to 6% among subjects with teeth missing due to trauma or agenesis. The main conclusions of this thesis were that (i) a check of whether one or more permanent incisors are missing will identify 65% of individuals with oligodontia and 84% of individuals missing nine teeth or more, (ii) evaluation of salivary secretion is indicated in children with oligodontia, (iii) a majority of individuals with oligodontia did not report other abnormal ectodermal organ function besides teeth, (iv) no clinical indicator discriminated between individuals with and without mutations in the tested genes, and more unidentified genes are involved in tooth morphogenesis, (v) EDARADD mutations are associated with isolated oligodontia, (vi) evaluation of orofacial function is indicated in individuals with ED, and many individuals with ED would benefit from orofacial skills training, (vii) dental implant placement is a rare treatment modality in children, (viii) individuals with hypohidrotic ED seem to present special challenges due to structural as well as direct effects of the mutations on bone, which seem to compromise osseointegration, (ix) central registers on signs and symptoms in individuals with rare disorders would help establish prevalences of various diagnoses and define treatment needs, and (x) quality registers for monitoring treatment outcomes of dental implants would promote early detection of risks and side-effects in individuals with rare disorders.