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An international advisory group met at the National Institutes of Health in Bethesda, Maryland in 2017, to discuss a new classification system for the ectodermal dysplasias (EDs) that would integrate both clinical and molecular information. We propose the following, a working definition of the EDs building on previous classification systems and incorporating current approaches to diagnosis: EDs are genetic conditions affecting the development and/or homeostasis of two or more ectodermal derivatives, including hair, teeth, nails, and certain glands. Genetic variations in genes known to be associated with EDs that affect only one derivative of the ectoderm (attenuated phenotype) will be grouped as non-syndromic traits of the causative gene (e.g., non-syndromic hypodontia or missing teeth associated with pathogenic variants of EDA "ectodysplasin"). Information for categorization and cataloging includes the phenotypic features, Online Mendelian Inheritance in Man number, mode of inheritance, genetic alteration, major developmental pathways involved (e.g., EDA, WNT "wingless-type," TP63 "tumor protein p63") or the components of complex molecular structures (e.g., connexins, keratins, cadherins)., (© 2019 Wiley Periodicals, Inc.)

Singleton-Merten syndrome (MIM 182250) is an autosomal dominant inherited disorder characterized by early onset periodontitis, root resorption, osteopenia, osteoporosis, and aortic valve or thoracic aorta calcification. The disorder can have significant intrafamilial phenotypic variability. Here, we present a mother and daughter with Singleton-Merten syndrome harboring a previously described pathogenic missense mutation, c.2465G>A p.(Arg822Gln), in IFIH1 (interferon induced with helicase C domain 1), encoding MDA5 (Melanoma Differentiation-Associated protein 5). These data confirm the pathogenicity of IFIH1 c.2465G>A p.(Arg822Gln) for Singleton-Merten syndrome and affirm the striking phenotypic heterogeneity of this disorder. In addition, we expand the Singleton-Merten phenotype by adding severe systemic lupus erythematosus (SLE) to the clinical picture. Investigations of known SLE genes as well as a single nucleotide polymorphism suggested to be involved in development of SLE were normal., (© 2017 Wiley Periodicals, Inc.)

Oral signs and symptoms are present in most ectodermal dysplasias (EDs). The aim of this article is to summarize some of the literature on current knowledge of oral manifestations and orofacial function in EDs. The review will focus on the most common forms where dental manifestations can be crucial for a differential diagnosis of ED among individuals with hypodontia and oligodontia, and preferably where the investigations included persons who had a genetically verified diagnosis. Disturbances in tooth development are common and can appear as tooth agenesis, variations in size and shape of teeth, defects in the mineralized tissues, and problems in tooth eruption. Abnormalities in number, size, and shape of teeth, and reduced salivary secretion, present in isolated oligodontia as well as in hypohidrotic ED and incontinentia pigmenti. In some more rare EDs these symptoms appear in combination with clefts of lip and/or palate in some affected individuals. Leukokeratosis in the oral mucosa presents in 70% of genetically confirmed cases of pachyonychia congenita. Also, orofacial function is often affected in ED, due to malformations, an incomplete dentition, and low salivary secretion which can compromise chewing, swallowing, and speech. In conclusion, there is a clinical overlap in oral signs and symptoms between isolated oligodontia and the most common EDs. Studies with genetically confirmed diagnoses and larger cohorts, as well as multicenter collaboration and the establishing of international registries, would create a basis for refined diagnostics, where oral examinations should be an integrated part of clinical assessment., (© 2014 Wiley Periodicals, Inc.)

A large proportion (>50%) of patients with isolated oligodontia were recently reported with WNT10A mutations. We have analyzed a population-based cohort of 102 individuals diagnosed with non-syndromic oligodontia and a mean of 8.2 missing teeth. The cohort included 94 families and screening of WNT10A identified that 26 probands (27.7%) had at least one WNT10A variant. When we included the MSX1, PAX9, AXIN2, EDA, EDAR, and EDARADD genes, 38.3% of probands were positive for a mutation. Biallelic WNT10A mutations were strongly associated with a larger number of missing teeth (11.09) when compared to both monoallelic WNT10 mutations (6.82) and the group without mutations in WNT10A, MSX1, PAX9, AXIN2, EDA, EDAR, or EDARADD (7.77). Genotype-phenotype analysis of individuals with WNT10A mutations showed that premolars were the most common missing teeth. Furthermore, biallelic WNT10A mutations were associated with absence of maxillary and mandibular molars as well as mandibular central incisors. Maxillary central incisors were always present. Thus, our study indicates that WNT10A mutations are associated with both the type and numbers of missing teeth. Furthermore, we show that this population-based cohort of isolated oligodontia had a considerably lower frequency of mutated WNT10A alleles and a lower mean number of missing teeth when compared to patients recruited from dental specialist centers., (© 2013 Wiley Periodicals, Inc.)

Oligodontia is defined as the congenital lack of six or more permanent teeth, excluding third molars. Oligodontia as well as hypodontia (lack of one or more permanent teeth) are highly heritable conditions associated with mutations in the AXIN2, MSX1, PAX9, EDA, and EDAR genes. Here we define the prevalence of mutations in the AXIN2, MSX1, PAX9, EDA, and EDAR genes, and the novel candidate gene EDARADD in a cohort of 93 Swedish probands with non-syndromic, isolated oligodontia. Mutation screening was performed using denaturing gradient gel electrophoresis and DNA sequence analysis. Analyses of the coding sequences of the six genes showed sequence alterations predicted to be damaging or potentially damaging in ten of 93 probands (10.8%). Mutations were identified in the EDARADD (n = 1), AXIN2 (n = 3), MSX1 (n = 2), and PAX9 (n = 4) genes, respectively. None of the 10 probands with mutations had other self-reported symptoms from ectodermal tissues. The oral parameters were similar when comparing individuals with and without mutations but a family history of oligodontia was three times more frequent for probands with mutations. EDARADD mutations have previously been reported in a few families segregating hypohidrotic ectodermal dysplasia and this is, to our knowledge, the first report of an EDARADD mutation associated with isolated oligodontia., (Copyright © 2011 Wiley-Liss, Inc.)

A study of the knowledge about dental health and diseases of youths in their late teens has been conducted. A 10-class questionnaire relating to dental caries and gingivitis/periodontitis was answered by three test groups (A, B, C) totalling seventy-eight 19-year-olds who, during a 3-year period, had undergone professional prophylaxis at different intervals. Nineteen young people of the same age without organized preventive measures since their last attendance at the public dental service constituted a control group (D). The test groups were found to have a significantly better knowledge of factors relating to gingivitis/periodontitis than the control group. In questions relating to caries there were no differences among the groups. Higher points were scored in knowledge of therapy and prevention than of the causes and symptoms of the dental diseases. Several regularly repeated sessions for professional prophylaxis did not lead to better knowledge than only a few. No consistent correlation was found for any of the groups between knowledge and both quantitative tooth cleaning, i.e. type and frequency of use of oral hygiene aids, and qualitative tooth cleaning, expressed as the occurrence of plaque and gingivitis. Nor were significant differences found in these respects between individuals with and without a caries increment during the observation period regardless of grouping.