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Hypohidrotic ectodermal dysplasia (HED) is a rare genetic disorder caused by mutational inactivation of a developmental pathway responsible for generation of tissues of ectodermal origin. The X-linked form accounts for the majority of HED cases and is caused by Ectodysplasin (EDA) pathogenic variants. We performed a combined analysis of 29 X-linked hypohidrotic ectodermal dysplasia (XLHED) families (including 12 from our previous studies). In addition to the classical triad of symptoms including loss (or reduction) of ectodermal structures, such as hair, teeth, and sweat glands, we detected additional HED-related clinical features including facial dysmorphism and hyperpigmentation in several patients. Interestingly, global developmental delay was identified as an unusual clinical symptom in many patients. More importantly, we identified 22 causal pathogenic variants that included 15 missense, four small in-dels, and one nonsense, splice site, and large deletion each. Interestingly, we detected 12 unique (India-specific) pathogenic variants. Of the 29 XLHED families analyzed, 11 (38%) harbored pathogenic variant localized to the furin cleavage site. A comparison with HGMD revealed significant differences in the frequency of missense pathogenic variants; involvement of specific exons and/or protein domains and transition/transversion ratios. A significantly higher proportion of missense pathogenic variants (33%) localized to the EDA furin cleavage when compared to HGMD (7%), of which p.R155C, p.R156C, and p.R156H were detected in three families each. Therefore, the first comprehensive analysis of XLHED from India has revealed several unique features including unusual clinical symptoms and high frequency of furin cleavage site pathogenic variants.

X-linked hypohidrotic dysplasia (XLHED), caused by mutations in the EDA gene, is a rare genetic disease that affects the development and function of the teeth, hair, nails, and sweat glands. The structural and functional consequences of caused by an ectodysplasin-A (EDA) mutations on protein phenotype, stability, and posttranslational modifications (PTMs) have not been well investigated. The present investigation involves five missense mutations that cause XLHED (L56P, R155C, P220L, V251M, and V322A) in different domains of EDA (TM, furin, collagen, and tumor necrosis factor [TNF]) from previously published papers. The deleterious nature of EDA mutant variants was identified using several computational algorithm tools. The point mutations induce major drifts in the structural flexibility of EDA mutant variants and have a negative impact on their stability, according to the 3D protein modeling tool assay. Using the molecular docking technique, EDA/EDA variants were docked to 10 EDA interacting partners, retrieved from the STRING database. We found a novel biomarker CD68 by molecular docking analysis, suggesting all five EDA variants had lower affinity for EDAR, EDA2R, and CD68, implying that they would affect embryonic signaling between the ectodermal and mesodermal cell layers. In silico research such as gene ontology, subcellular localization, protein-protein interaction, and PTMs investigations indicates major functional alterations would occur in EDA variants. According to molecular simulations, EDA variants influence the structural conformation, compactness, stiffness, and function of the EDA protein. Further studies on cell line and animal models might be useful in determining their specific roles in functional annotations.

Aim: Ectodermal dysplasia is a rare hereditary disease that arises from a developmental disorder of 2 or more ectoderm-derived tissues. Ectodermal dysplasia is seen in 3 different types: anhidrotic, hypohidrotic, and hidrotic. Its anhidrotic and hypohidrotic types are the most common. This study presents the intraoral findings and dental treatment approach of a case diagnosed with hidrotic ectodermal dysplasia that demonstrates the typical characteristics of the disease, such as anodontia, hypohydrosis (reduced sweating), hypotrichosis (sparse hair), and loss of vertical dimension. Methodology: A 5-year-old male patient presented to the clinic of the Prosthetic Dental Treatment Department of the School of Dentistry at Dicle University on 25.10.2020 with complaint of missing teeth. A genetic analysis conducted in 2016 showed that he was a homozygous carrier of the p.Cys148Arg (c.442 T>C) mutation on the 5th exon of the ectodysplasin-A receptor (EDAR) gene. The mutation detected in the patient was associated with ectodermal dysplasia. An extraoral clinical examination revealed sparse hair, eyebrows, and eyelashes; soft, smooth, and dry skin; thin, linear wrinkles around the eyes and the lips; drooping, thickened lips; a sunken nose; fractured nails; hyperthermia due to lack of sweat glands; hyperkeratosis in the skin and soles of the feet; 2 nipples on one side of the chest; and reduced vertical facial height. An intraoral examination revealed anodontia; there were no teeth on the maxilla or the mandible and no radiographically identified tooth germ. Dry mouth due to a lack of sufficient saliva was another finding. Conclusion: In this case report, in the presence of anodontia, a removable total prosthesis, which is a non-invasive treatment option, was applied. Production of endosseous implants was postponed for a later time following the patient’s growth and development. How to cite this article: Gökçe D, Ayna E, Seyfioğlu Polat Z. Prosthetic rehabilitation of a hypohidrotic ectodermal dysplasia patient: A case report. Int Dent Res 2021;11(Suppl.1):292-8. https://doi.org/10.5577/intdentres.2021.vol11.suppl1.43 Linguistic Revision: The English in this manuscript has been checked by at least two professional editors, both native speakers of English.

The primary anatomical defect leading to periventricular nodular heterotopia occurs within the neural progenitors along the neuroepithelial lining of the lateral ventricles and results from a defect in the initiation of neuronal migration, following disruption of the neuroependyma and impaired neuronal motility. Growing evidence indicates that the FLNA-dependent actin dynamics and regulation of vesicle formation and trafficking by activation of ADP-ribosylation factors (ARFs) can play an important role in this cortical malformation. We report the first inherited variant of ARF1 in a girl with intellectual disability and periventricular nodular heterotopia who inherited the variant from the father with previously undiagnosed single nodular heterotopia and mild clinical expression. Additionally, both patients presented some features suggestive of hypohidrotic ectodermal dysplasia. These clinical features showed similarities to those of three previously reported cases with ARF1 missense variants, confirming that haploinsufficiency of this gene causes a recognisable neurological disorder with abnormal neuronal migration and variable clinical expressivity.

Hypohidrotic ectodermal dysplasia (HED) is a genetic disorder characterized by hypohidrosis, hypodontia, and hypotrichosis. Autosomal forms of the disease are caused by mutations in either EDAR or EDARADD. To date, the underlying pathomechanisms for HED resulting from EDARADD mutations have not fully been disclosed. In this study, we performed detailed in vitro analyses in order to characterize three dominantly inherited missense mutations, p.D120Y, p.L122R, and p.D123N, and one recessively inherited missense mutation, p.E152K, in the EDARADD gene. Nuclear factor (NF)-κB reporter assays demonstrated that all the mutant EDARADD showed reduction in activation of NF-κB. Importantly, p.D120Y-, p.L122R-, and p.D123N-mutant EDARADD slightly reduced the NF-κB activity induced by wild-type EDARADD in a dominant negative manner. Co-immunoprecipitation assays showed that all of the mutant EDARADD were capable of binding to EDAR and wild-type EDARADD. Additional co-immunoprecipitation assays revealed that p.D120Y-, p.L122R-, and p.D123N-mutant EDARADD markedly prevented the interaction between EDAR and wild-type EDARADD, which further indicated a dominant negative effect by these mutations. Finally, we found that p.D120Y-, p.L122R-, and p.D123N-mutant EDARADD completely lost the ability to bind with TRAF6, while p.E152K-mutant EDARADD showed a mild reduction in the affinity. Our findings will provide crucial information toward unraveling the molecular mechanisms how EDARADD gene mutations cause the disease.

In the present report, we describe targeted next-generation sequencing of the EDA gene of a male poodle with a clinical and histopathological diagnosis of X-linked hypohidrotic ectodermal dysplasia. The result was compared with the reference sequence and with the result of the sequencing of a normal dog's EDA gene. No point variant, small deletion or insertion were found in the exons and splice sites, but a transition and a transversion were found in the intron 6' and 3' UTR, respectively. The cause of the dysplasia of the affected dog in this study is neither a point variant nor a small deletion or insertion in the exons and splice sites of the EDA gene. Therefore, patients with phenotype of XLHED may have other types of variants in the EDA gene or variants in other genes of the EDA signalling pathway.

BackgroundHypohidrotic Ectodermal Dysplasia (HED) is a genetic disorder which affects structures of ectodermal origin. X-linked hypohidrotic ectodermal dysplasia (XLHED) is the most common form of disease. XLHED is characterized by hypotrichosis, hypohydrosis and hypodontia. The cardinal features of classic HED become obvious during childhood.Identification of a hemizygous EDA pathogenic variant in an affected male confirms the diagnosis.Case presentationWe report on a male newborn with the main clinical characteristics of the X-linked HED including hypotrichosis, hypodontia and hypohidrosis. Gene panel sequencing identified a new hemizygous missense variant of uncertain significance (VUS) c.1142G > C (p.Gly381Ala) in the EDA gene, located on the X chromosome and inherited from the healthy mother.ConclusionDespite the potential functional impact of VUS remains uncharacterized, our goal is to evaluate the clinical potential consequences of missense VUS on EDA gene. Even if the proband’s phenotype is characteristic for classic HED, further reports of patients with same clinical phenotype and the same genomic variant are needed to consider this novel VUS as responsible for the development of HED.

A 4-year-old boy with oligodontia, presenting only maxillary central conical-shaped incisors, received his first complete dentures. He could wear dentures for a better appearance; however, had difficulty eating because of no experience with chewing. To motivate and improve his chewing practice, color-changeable chewing gum was provided, and the times of color changing recorded. The patient was interested in this chewing training, and the recorded times became shorter, implying better masticatory performance. Therefore, color-changeable chewing gum would motivate patients to have chewing training, and might improve their masticatory function.

Aim. The management of hypohidrotic ectodermal dysplasia with oligodontia in Class-I malocclusion in late mix dentition. Case Report. An 11-year-old boy with ED was treated and managed by means of interceptive orthodontic treatment accompanied by direct and indirect restorative methods in a successful manner. The patient was prepared to receive definitive oral rehabilitation with dental implants for the missing teeth when the patient reaches a suitable age. The patient was followed for 5 years from the beginning of treatment. Conclusion. Management of the child with ectodermal dysplasia with oligodontia was a real challenge. Early diagnosis, necessary investigation, and providing age-appropriate multidisciplinary treatment were key steps in successful outcomes. The objectives were not only just orthodontic or paedodontics but also prosthetic and psychological.

Genes associated with the WNT pathway play an important role in the etiology of tooth agenesis. Low-density lipoprotein receptor–related protein 6 encoding gene ( LRP6) is a recently defined gene that is associated with autosomal dominant inherited tooth agenesis. Here, we aimed to identify novel LRP6 mutations in patients with tooth agenesis and investigate the significance of Lrp6 during tooth development. Using whole-exome sequencing, we identified 4 novel LRP6 heterozygous mutations (c.2292G>A, c.195dup, c.1095dup, and c.1681C>T) in 4 of 77 oligodontia patients. Notably, a patient who carried a nonsense LRP6 mutation (c.2292G>A; p.W764*) presented a hypohidrotic ectodermal dysplasia phenotype. Preliminary functional studies, including bioinformatics analysis and TOP-/FOP-flash reporter assays, demonstrated that the activation of WNT/β-catenin signaling was compromised as a consequence of LRP6 mutations. RNAscope in situ hybridization revealed dynamic and special changes of Lrp6 expression during murine tooth development from E11.5 to E16.5. It was noteworthy that Lrp6 was specifically expressed in the epithelium at E11.5 to E13.5 but was expressed in both dental epithelium and dental papilla from E14.5 and persisted in both tissues at later stages. Our study broadens the mutation spectrum of human tooth agenesis and is the first to identify a LRP6 mutation in patients with hypohidrotic ectodermal dysplasia and reveal the dynamic expression pattern of Lrp6 during tooth development. Information from this study is conducive to understanding the functional significance of Lrp6 on the biological process of tooth development.

Nonsyndromic oligodontia is a rare congenital anomaly. Mutations in the ectodysplasin A receptor (EDAR) gene are the primary cause of hypohidrotic ectodermal dysplasia but are rarely reported in nonsyndromic oligodontia. This study investigated EDAR mutations in multiplex nonsyndromic oligodontia and comparatively analyzed the EDAR- and EDA-related tooth agenesis patterns. Mutation screening was carried out using whole-exome sequencing and familial segregation. Evolutionary conservation and conformational analyses were used to evaluate the potential pathogenic influence of EDAR mutants. EDAR mutations were found to occur in 10.7% of nonsyndromic oligodontia cases. We reported seven heterozygous mutations of EDAR, including five novel mutations (c.404G>A, c.871G>A, c.43G>A, c.1072C>T, and c.1109T>C) and two known mutations (c.319A>G and c.1138A>C). Genotype-phenotype correlation analysis demonstrated that the EDAR-related tooth agenesis pattern was markedly different from EDA. The mandibular second premolars were most frequently missing (57.69%) in EDAR-mutated patients. Our results provide new evidence for the genotypic study of nonsyndromic oligodontia and suggest that EDAR haploinsufficiency results in nonsyndromic tooth agenesis. Furthermore, the distinct pattern between EDAR- and EDA-related tooth agenesis can be used as a guide for mutation screening during the clinical genetic diagnosis of this genetic disorder.

Hypohidrotic ectodermal dysplasia (HED) is a congenital anomaly characterized by hypohydrosis, hypotrichosis and hypodontia. Mutations in at least four genes (EDAR, EDARADD, WNT10A, TRAF6) have been reported to cause both autosomal recessive and autosomal dominant forms of HED. Mutations in two other genes (EDA and IKBKG) have been reported to cause X-linked HED. To clinically characterize three consanguineous families (A-C) segregating with autosomal recessive HED and identify possible disease-causing variants of EDAR and EDARADD genes. The genes, EDAR and EDARADD, were sequenced in Family A and C, and exome sequencing was performed in Family B. Additionally, in Family A and C, the effect of the identified variants was examined by analysis of EDAR mRNA, extracted from hair follicles from both affected and unaffected members. Sequence analysis revealed three possible disease-causing EDAR variants including a novel splice acceptor site variant (IVS3-1G > A) in Family A and two previously reported mutations (p.[Ala26Val], p.[Arg25*]) in the two other families. Previously, the nonsense variant p.(Arg25*) was reported only in the heterozygous state. Analysis of the RNA, extracted from hair follicles, revealed skipping of a downstream exon in EDAR and complete degradation of EDAR mRNA in affected members in family A and C, respectively. Computational modelling validated the pathogenic effect of the two variants identified in Family B and C. The three variants reported here expand the spectrum of EDAR mutations associated with HED which may further facilitate genetic counselling of families segregating with similar disorders in the Pakistani population.

Objective Hypohidrotic ectodermal dysplasia (HED) is a hereditary disorder characterized by abnormal structures and functions of the ectoderm-derived organs, including teeth. HED patients exhibit a variety of dental symptoms, such as hypodontia. Although disruption of the EDA/EDAR/EDARADD/NF-κB pathway is known to be responsible for HED, it remains unclear whether this pathway is involved in the process of enamel formation. Experimental subjects and methods To address this question, we examined the mice overexpressing Ikkβ (an essential component required for the activation of NF-κB pathway) under the keratin 5 promoter (K5-Ikkβ). Results Upregulation of the NF-κB pathway was confirmed in the ameloblasts of K5-Ikkβ mice. Premature abrasion was observed in the molars of K5-Ikkβ mice, which was accompanied by less mineralized enamel. However, no significant changes were observed in the enamel thickness and the pattern of enamel rods in K5-Ikkβ mice. Klk4 expression was significantly upregulated in the ameloblasts of K5-Ikkβ mice at the maturation stage, and the expression of its substrate, amelogenin, was remarkably reduced. This suggests that abnormal enamel observed in K5-Ikkβ mice was likely due to the compromised degradation of enamel protein at the maturation stage. Conclusion Therefore, we could conclude that the overactivation of the NF-κB pathway impairs the process of amelogenesis.

We report the case of an adolescent with hypohidrotic ectodermal dysplasia, who had obsessive-compulsive disorder and was later diagnosed with body dysmorphic disorder (BDD). BDD is a highly distressing, adolescent-onset disorder that may lead to social isolation, the development of comorbid mental health disorders and suicidality. Patients typically lack insight into their BDD and frequently present to dermatologists for medical treatment. In this paper, we address the challenges faced when working with patients with BDD.

In X-linked hypohidrotic ectodermal dysplasia, the most frequent ectodermal dysplasia, an inherited deficiency of the signalling protein ectodysplasin A1 (EDA1) impairs the development of the skin and its appendages, various eccrine glands, and dentition. The severe hypohidrosis common to X-linked hypohidrotic ectodermal dysplasia patients may lead to life-threatening hyperthermia, especially during hot weather or febrile illness. Fc-EDA, an EDA1 replacement protein known to prevent the disease in newborn animals, was tested in 2 clinical trials (human adults and neonates) and additionally administered under compassionate use to 3 infants in utero. The data support the safety of Fc-EDA and efficacy if applied prenatally. Anti-drug antibodies were detected after intravenous administration in adult males and nonpregnant females, but not in pregnant women when Fc-EDA was delivered intra-amniotically. Most importantly, there was no detectable immune response to the investigational drug in neonates treated by intravenous infusions and in infants who had received Fc-EDA in utero. In conclusion, the safety profile of this drug encourages further development of prenatal EDA1 replacement therapy.

The objective of this study was to review the published literature on X-linked hypohidrotic ectodermal dysplasia (XLHED) for the prevalence and characteristics of three features of XLHED: hypodontia, hypohidrosis, and hypotrichosis. A systematic search of English-language articles was conducted in May 2019 to identify publications with information on any of the three features of XLHED. We excluded studies with five or fewer participants, that did not specify X-linked inheritance or an EDA mutation, and discussed only management of features. The weighted means for total missing teeth, location of missing teeth, prevalence of reduced and absent sweating ability, and sparse or absent hair were analyzed across all studies. Additional findings for hypodontia, hypohidrosis, and hypotrichosis were summarized qualitatively. Twenty publications (18 studies) were accepted. Reported findings for males tended to be more informative than for carrier females. The weighted mean for missing teeth for affected males was 22.4 (range: 10-28) and carrier females was 3.4 (range: 0-22). The most common conserved teeth for males were the canines. The most common missing teeth for females were the maxillary lateral incisors. The weighted mean prevalence of reduced or absent sweating ability was 95.7% for males and 71.6% for females. The weighted mean prevalence for hypotrichosis was 88.1% for males and 61.6% for females. This systematic review provides insight into the prevalence, characteristics, and variability of the three classic features of XLHED. These findings provide detailed natural history information for families with XLHED as well as key characteristics that can aid in diagnosis.

A 56-year-old woman with hypohidrotic ectodermal dysplasia presented with a 10-year history of persisting wart-like skin lesions on her feet. Biopsy revealed changes of eccrine syringofibroadenoma. These lesions are rare, with only nine case reports describing an association with ectodermal dysplasia of hidrotic type (Clouston and Schopf's syndrome). To our knowledge, this is the first case of eccrine syringofibroadenoma developing in the hypohidrotic/anhidrotic subtype of ectodermal dysplasia.

X-linked hypohidrotic ectodermal dysplasia (XLHED) is a rare congenital genetic disorder caused by mutations in the ectodysplasin A gene, resulting in dysplasia or complete absence of teeth, hair, and sweat glands. XLHED is rarely diagnosed prenatally. We describe a case of XLHED diagnosed with prenatal sonography and umbilical cord blood gene testing.

Hereditary ectodermal dysplasias are a complex group of inherited disorders characterised by abnormalities in two or more ectodermal derivatives (skin, nails, sweat glands, etc.). There are two main types of these disorders – hidrotic and hypohidrotic/anhidrotic ectodermal dysplasias. Hypohidrotic ectodermal dysplasia (HED) or Christ-Siemens-Touraine syndrome (OMIM: 305100 ) occurs in 1 out of 5000–10,000 births [19] and has an X-linked recessive inheritance pattern (X-linked hypohydrotic ectodermal dysplasia – XLHED) [2] . The main cause of XLHED is a broad range of pathogenic variants in the EDA gene (HGNC:3157, Xq12-13) which encodes the transmembrane protein ectodysplasin-A [4] . We report here the case of a patient with a novel inherited allelic variant in the EDA gene – NM_001399.5:c.337C>T (p.Gln113*) – in the heterozygous state. Targeted family member screening was conducted and other carriers of this EDA gene pathogenic variant were identified and phenotypically characterised. The patient subsequently underwent in vitro fertilisation with preimplantation genetic testing for monogenic diseases (PGT-M).

X-linked hypohidrotic ectodermal dysplasia (XLHED) is the most common form of ectodermal dysplasia. Clinical and genetic heterogeneity between different ectodermal dysplasia types and evidence of incomplete penetrance and variable expressivity increase the potential for misdiagnosis. We describe a family with X-linked hypohidrotic ectodermal dysplasia (XLHED) presenting with variable expressivity of symptoms between affected siblings. In addition to the classical signs of hypohidrosis, hypotrichosis and hypodontia, the index patient—a 5 year old boy, also presented with a severe atopy phenotype that was not observed in the other two affected brothers. Exome sequencing in the index and the mother identified a pathogenic nonsense variant in EDA (NM_001399.4: c.766 C>T; p. Gln256Ter). This study highlights how exome sequencing was crucial in establishing a precise molecular diagnosis of XLHED by enabling us to rule out other differential diagnoses including NEMO deficiency syndrome, that was initially presented as a clinical diagnosis to the family.

X-linked hypohidrotic ectodermal dysplasia with the cardinal symptoms hypodontia, hypotrichosis and hypohidrosis is caused by a genetic deficiency of ectodysplasin A1 (EDA1). Prenatal EDA1 replacement can rescue the development of skin appendages and teeth. Tabby mice, a natural animal model of EDA1 deficiency, additionally feature a striking kink of the tail, the cause of which has remained unclear. We studied the origin of this phenomenon and its response to prenatal therapy. Alterations in the distal spine could be noticed soon after birth, and kinks were present in all Tabby mice by the age of 4 months. Although their vertebral bones frequently had a disorganized epiphyseal zone possibly predisposing to fractures, cortical bone density was only reduced in vertebrae of older Tabby mice and even increased in their tibiae. Different availability of osteoclasts in the spine, which may affect bone density, was ruled out by osteoclast staining. The absence of hair follicles, a well-known niche of epidermal stem cells, and much lower bromodeoxyuridine uptake in the tail skin of 9-day-old Tabby mice rather suggest the kink being due to a skin proliferation defect that prevents the skin from growing as fast as the skeleton, so that caudal vertebrae may be squeezed and bent by a lack of skin. Early postnatal treatment with EDA1 leading to delayed hair follicle formation attenuated the kink, but did not prevent it. Tabby mice born after prenatal administration of EDA1, however, showed normal tail skin proliferation, no signs of kinking and, interestingly, a normalized vertebral bone density. Thus, our data prove the causal relationship between EDA1 deficiency and kinky tails and indicate that hair follicles are required for murine tail skin to grow fast enough. Disturbed bone development appears to be partially pre-determined in utero and can be counteracted by timely EDA1 replacement, pointing to a role of EDA1 also in osteogenesis.

This case study highlights a rare entity of Christ Siemens Touraine Syndrome. Ectodermal dysplasia is a rare entity with incidence of 1 in 1,00,000 births with male predominance. Most commonly it presents with appendageal abnormality with facial dysmorphism. The two most common types of ectodermal dysplasias are hypohidrotic ectodermal dysplasia (Christ-Siemens-Touraine syndrome) and hidrotic ectodermal dysplasia (Clouston syndrome). Clinical recognition varies depending on severity of symptoms and associated complications. The prognosis is good after infancy if diagnosed early with appropriate management of complications. Here we present a case of eight month old female with Hypohidrotic Ectodermal Dysplasia. Management usually demands a multidisciplinary team approach. It includes protection from exposure to high temperatures, early dental evaluation for adequate nutrition, removable prosthodontics and dental implants, use of lacrimal tears to prevent corneal damage.

Ectodermal dysplasia is a disease that affects components of body with ectodermal origin, so it is manifested by thin hair, malformed or missing teeth and lack of sweating. In this case, I present a 4 year old boy with hypohidrotic ectodermal dysplasia. He had psychological issues and difficulty in eating. In this young child, with prosthetic treatment that included partial removable denture, his problems was dissolved.

This is a first case report of a patient with hypohidrotic ectodermal dysplasia from Oman, who was found to carry a mutation in the EDAR gene after candidate gene selection based on regions of homozygosity in his genome.

Background Ectodermal dysplasia is a rare genetic disorder that affects ectodermally derived structures, including teeth, nails, hair, and sweat glands. Hypohidrotic ectodermal dysplasia is the most common type, with oligodontia being the most striking dental feature. Prosthetic rehabilitation in children with ectodermal dysplasia is an important step toward improving their overall quality of life. The fixed prosthesis has the advantages of being more stable in the mouth with good child compliance and a good aesthetic outcome. Case presentation Our patient was a 5-year-old Middle Eastern boy with oligodontia caused by ectodermal dysplasia. He was managed by fabrication of an upper functional space maintainer and a lower fixed partial denture to restore occlusion, masticatory function, aesthetics, and overall quality of life. Conclusions The use of the fixed prosthesis in children is a new and evolving treatment modality that resolves many of the issues caused by removable prostheses. It accommodates jaw growth in the mandible, reduces the need to remake the prosthesis, and has an overall better aesthetic outcome.

Purpose Ectodermal dysplasias are characterized by developmental abnormalities in ectodermal structures. Hypohidrotic ectodermal dysplasias (HED) are the most common subtype. They are most commonly inherited via X-linked recessive routes. We report on a novel ectodysplasin-A (EDA) mutation that is expected to be involved in pathogenesis of HED. Methods Hypohidrotic ectodermal dysplasia genes, including EDA, EDAR and EDARADD, were analyzed using next-generation sequencing (NGS). The detected mutation on the EDA gene was confirmed in the patient and his mother using Sanger sequencing. Results The patient presented with adontia, absence of gum development, hyperthermia and hypohidrosis. Our genetic analysis of the patient revealed a novel frameshift hemizygous mutation (c.898_924 + 8del35ins4CTTA) on the EDA gene. The patient’s mother showed a mild HED phenotype. Direct sequencing of the EDA gene in the region where her son had the mutation showed the same mutation in a heterozygous state. Conclusion We identified a novel frameshift mutation in the EDA gene in an Iranian patient affected by X-linked HED. The difference between our patient’s symptoms and those recorded for some previous subjects may be due to the differences in the mutations involved. Electronic supplementary material The online version of this article (10.1186/s11658-019-0174-9) contains supplementary material, which is available to authorized users.

Hypohidrotic ectodermal dysplasia (HED) is a rare genetic disorder characterized by hypotrichosis, hypohidrosis and hypodontia. The disease shows X-linked recessive, autosomal dominant or autosomal recessive inheritance traits. The X-linked form of HED is caused by mutations in the EDA gene, while autosomal forms result from mutations in either EDAR or EDARADD genes. Regarding recessive mutations in the EDAR gene, the pathomechanisms have been well characterized. However, it has remained largely unknown how dominant mutations in the EDAR cause HED. In this study, we performed in vitro analyses for a dominant EDAR gene mutation, p.F398*, as a representative. We showed that the p.F398* mutant EDAR completely lost its affinity to EDARADD, and suppressed the downstream nuclear factor-κB activation induced by wild-type EDAR in a dominant-negative manner. Furthermore, we demonstrated that the mutant EDAR was capable of binding with the wild-type EDAR, which led to reduced interaction between the wild-type EDAR and EDARADD. Our findings not only underscore an essential role of the interaction between EDAR and EDARADD in ectodermal development, but also disclose, in part, the molecular basis of autosomal dominant HED.

X-linked hypohidrotic ectodermal dysplasia (XLHED) is caused by defects in the EDA gene that inactivate the function of ectodysplasin A1 (EDA1). This leads to abnormal development of eccrine glands, hair follicles, and teeth, and to frequent respiratory infections. Previous studies in the naturally occurring dog model demonstrated partial prevention of the XLHED phenotype by postnatal administration of recombinant EDA1. The results suggested that a single or two temporally spaced injections of EDI200 prenatally might improve the clinical outcome in the dog model. Fetuses received ultrasound-guided EDI200 intra-amniotically at gestational days 32 and 45, or 45 or 55 alone (of a 65-day pregnancy). Growth rates, lacrimation, hair growth, meibomian glands, sweating, dentition, and mucociliary clearance were compared in treated and untreated XLHED-affected dogs, and in heterozygous and wild-type control dogs. Improved phenotypic outcomes were noted in the earlier and more frequently treated animals. All animals treated prenatally showed positive responses compared with untreated dogs with XLHED, most notably in the transfer of moisture through paw pads, suggesting improved onset of sweating ability and restored meibomian gland development. These results exemplify the feasibility of ultrasound-guided intra-amniotic injections for the treatment of developmental disorders, with improved formation of specific EDA1-dependent structures in dogs with XLHED.

Introduction Hypohidrotic ectodermal dysplasia (HED) is a rare disease that results from the abnormal development of the ectodermal germ layer in early embryogenesis. In these patients, hypoplasia of Meibomian glands is one of the most frequent ophthalmological manifestations. The main aim of this study is to evaluate the usefulness of meibography for the morphology of Meibomian glands in a group of patients with HED, and to compare it with a control group. Methods A total of 14 eyes of 7 patients diagnosed with HED were included, and 32 eyes of 16 patients were included as a control group. The meibographic study was carried out using CA-800 Corneal Analyser (Topcon®). Grading of images was assessed by a meibomian gland atrophy score: grade 0, no alterations; grade 1, ≤25% gland atrophy; grade 2, 25% to 50% gland atrophy; grade 3, 51% to 75% gland atrophy; and grade 4 >75% gland atrophy. Both groups were compared using the Mann–Whitney U non-parametric test. Results All patients with HED showed some degree of gland atrophy, with 57% showing severe atrophy (>75% of gland atrophy), 35.8% with a grade 3, and 7.2% grade 2. The mean grade of glandular atrophy in HED was 3 (1–4). In the control group, 62.5% had no involvement (grade 0), with 28.1% showing grade 1 and 9.4% grade 2 gland atrophy. The mean glandular atrophy grade within the control group was 0 (0–2). There were statistically significant differences between both groups. Conclusions Meibography is a simple diagnostic tool that allows to differentiate between patients without disease and those with HED.

Hypohidrotic ectodermal dysplasia (HED) is a rare genetic condition resulting from defective development of ectodermal derivatives, such as hair, teeth, and sweat glands. Autosomal recessive (AR) forms of HED may be caused by pathogenic variants of the ectodysplasin A1 receptor (EDAR) gene that encodes a receptor involved in the NF-κB signaling pathway. Here, we describe three cases of AR-HED in families of Turkish, Austrian, and German-American origin (with or without known consanguinity). In these cases, two out-of-frame deletions and a pathogenic missense variant of EDAR were found to be disease-causing due to reduced availability of the respective messenger RNA or impaired interaction of the encoded protein with its binding partner leading to diminished signal transduction. The same missense variant, c.1258C>T (p.Arg420Trp), has actually been reported to be restricted to the Icelandic population and to be associated with non-syndromic tooth agenesis but not HED. As our patient has no known relationship to Icelandic individuals and displays a rather severe HED phenotype, we suggest that EDAR-Arg420Trp is a more widespread variant, possibly with variable clinical expressivity.

X-linked hypohidrotic ectodermal dysplasia (XLHED; OMIM 305100) is the most common form of ectodermal dysplasia, presenting with the triad of hypotrichosis, hypodontia, and hypohidrosis. This disorder is caused by mutations in EDA, which encodes ectodysplasin A, a member of the tumor necrosis factor superfamily. In this study, we describe clinical and genetic characteristics of 10 Korean XLHED patients (9 males, 1 female) from 9 families. Nine out of the 10 patients manifested the cardinal triad of symptoms. Six patients had a positive family history, while 2 patients were brothers. The most common initial presentation was hypotrichosis or hypodontia, while 1 patient presented with recurrent high fever in early infancy. Sanger sequencing of the EDA gene was performed and revealed 9 different mutations. Three had been reported previously, and 6 were novel mutations. One female patient, carrying a previously reported missense mutation, might be affected by skewed X-inactivation. This is the first observational study investigating genetically confirmed XLHED patients in Korea. To provide appropriate supportive care and genetic counseling, clinicians should consider the possibility of XLHED in the differential diagnosis of recurrent fever in infants, as well as recognize the typical triad of symptoms.

Ectodermal dysplasias (ED) are a group of rare genetic disorders characterized by congenital defects involving two or more ectodermal structures. Christ-Siemens-Touraine syndrome or hypohidrotic ectodermal dysplasia is the commonest form of ED. Hypohidrotic ectodermal dysplasia (HED) is an X-linked disorder characterized by excessively dry skin due to the absence of sweat glands (anhidrosis), sparse body hair especially on the scalp and eyebrows (hypotrichosis), brittle nails, absence of sebaceous glands (asteatosis) and malformed or absent teeth. Oral manifestations include oligodontia or complete anodontia, conical teeth, underdeveloped alveolar ridges, generalized spacing and delayed eruption of permanent teeth. This case report discusses a classical case of HED and the options for rehabilitation in a growing patient. A thorough knowledge about the clinical manifestations of ED will lead to proper diagnosis and appropriate treatment plan thereby leading to significant improvements in esthetics, phonetics and masticatory function in ED patients, which in turn leads to improved quality of life in these individuals. How to cite this article Abdulla AM, Almaliki AY, Shakeela NV, et al. Prosthodontic Management of a Pediatric Patient with Christ-Siemens-Touraine Syndrome: A Case Report. Int J Clin Pediatr Dent 2019;12(6):569–572.

In this study, we present a detailed phenotype description and genetic elucidation of the first case of X-linked hypohidrotic ectodermal dysplasia in the shorthaired standard Dachshund. This condition is characterized by partial congenital hypotrichosis, missing and malformed teeth and a lack of eccrine sweat glands. Clinical signs including dental radiographs and histopathological findings were consistent with ectodermal dysplasia. Pedigree analysis supported an X-recessive mode of inheritance. Whole-genome sequencing of one affected puppy and his dam identified a 1-basepair deletion within the ectodysplasin-A (EDA) gene (CM000039.3:g.54509504delT, c.458delT). Sanger sequencing of further family members confirmed the EDA:c.458delT-variant. Validation in all available family members, 37 unrelated shorthaired standard Dachshunds, 128 further Dachshunds from all other coat and size varieties and samples from 34 dog breeds revealed the EDA:c.458delT-variant to be private for this family. Two heterozygous females showed very mild congenital hypotrichosis but normal dentition. Since the dam is demonstrably the only heterozygous animal in the ancestry of the affected animals, we assume that the EDA:c.458delT-variant arose in the germline of the granddam or in an early embryonic stage of the dam. In conclusion, we detected a very recent de-novo EDA mutation causing X-linked hypohidrotic ectodermal dysplasia in the shorthaired standard Dachshund.

The Ectodermal Dysplasias generally present orofacial manifestations, such as skeletal discrepancies and dental alterations. Therefore, the role of a paediatric dentist in the detection and recognition of these repercussions can be crucial in early diagnosis of the disease. The oral rehabilitation of paediatric patients with this condition is extremely important, ideally, at a very early stage, yet contributing for the re-establishment of normal chewing, swallowing and phonetics functions, and, naturally, aesthetics increase. The purpose of this narrative review aims to elucidate dentists about their role in the detection, diagnosis, treatment and monitoring of the Ectodermal Dysplasia’ oral manifestations in paediatric patients, through the presentation of general physical and specific craniofacial characteristics.

La Displasia Ectodérmica Hipohidrótica (DEH) o síndrome de Christ-Siemens-Touraine, es una rara enfermedad de carácter congénito, siendo afectado uno o varios componentes del tejido ectodérmico. Caracterizado por hipohidrosis, hipotricosis e hipodoncia. La mayoría de los casos se relaciona con una herencia recesiva ligada al cromosoma X, afectándose por consiguiente en los varones, pero también existen otras formas de herencia autosómica dominante y recesiva. Se presenta el caso clínico de un niño de 3 años 5 meses con oligodoncia y reabsorción de los procesos alveolares por ausencia total de las piezas deciduas, por lo que se realiza la rehabilitación protésica con prótesis total removible, como resultado se logra aumento de la dimensión vertical, mejora de la fonación, masticación, habla y la autoestima del paciente.

Recent advances in biology and bioinformatics permit the better classification of rare disorders, the identification of signaling pathways, and finally the identification of promising therapeutic targets. We illustrate these advances in the field of genodermatoses by two examples: a mosaic disorder spectrum known as PIK3CA-related overgrowth spectrum (PROS) and X-linked hypohidrotic ectodermal dysplasia the most frequent form of ectodermal dysplasia.

Background Hypohidrotic ectodermal dysplasia (HED) is the most common form of ectodermal dysplasia and is mainly associated with mutations in the EDA, EDAR, and EDARADD responsible for the development of ectodermal‐derived structures. HED displays different modes of inheritance according to the gene that is involved, with X‐linked EDA‐related HED being the most frequent form of the disease. Methods Two families with tooth agenesis and manifestations of HED underwent clinical examination and EDA, EDAR, and EDARADD genetic analysis. The impact of the novel variant on the protein was evaluated through bioinformatics tools, whereas molecular modeling was used to predict the effect on the protein structure. Results A novel missense variant was identified in the EDAR (c.287T>C, p.Phe96Ser) of a female child proband and her mother, accounting for autosomal dominant HED. The genetic variant c.866G>A (p.Arg289His) in EDA, which has been previously described, was observed in the male proband of another family confirming its role in X‐linked HED. The inheritance model of the missense mutation showed a different relationship with X‐linked HED and non‐syndromic tooth agenesis. Conclusion Our findings provide evidence of variable expression of HED in heterozygous females, which should be considered for genetic counseling, and different modes of inheritance related to tooth development., In this study, two families with clinical manifestations of hypohidrotic ectodermal dysplasia (HED) were investigated. The novel missense variant NM_022336.4:c.287T>C (p.Phe96Ser) in EDAR was identified in family A. This finding strongly suggests that the EDAR mutation in exon 4 is the cause of the disease with autosomal dominant inheritance because of its phenotypic manifestation also in heterozygosity and family segregation. The genetic variant c.866G>A (p. Arg289His) in EDA, which has been previously described, was observed in the male proband of another family confirming its role in X‐linked HED. Our findings provide evidence of variable expression of HED in heterozygous females, which should be considered for genetic counseling, and different modes of inheritance related to tooth development.

A 17-month old boy was referred to the genetic clinic in view of anodontia, hypohidrosis, scalp hypotrichosis, atrichia of the eyelashes, xerotic skin and a short columella. A diagnosis of X-Linked hypohidrotic ectodermal dysplasia (XLHED) was considered. The boy was born to healthy non-consanguineous parents of Maltese-Caucasian ethnicity at 38 weeks by emergency lower segment Caesarean section in view of fetal decelerations in the setting of documented intrauterine growth restriction (birth weight was 2.49kg [2.5th centile for age]). The genetic family history of the patient was unremarkable.

Genetic deficiency of ectodysplasin A (EDA) causes X-linked hypohidrotic ectodermal dysplasia, a congenital condition characterized by the absence or abnormal formation of sweat glands, teeth, and several skin appendages. Stimulation of the EDA receptor (EDAR) with agonists in the form of recombinant EDA or anti-EDAR antibodies can compensate for the absence of Eda in a mouse model of Eda deficiency, provided that agonists are administered in a timely manner during fetal development. Here we provide detailed protocols for the administration of EDAR agonists or antagonists, or other proteins, by the intravenous, intraperitoneal, and intra-amniotic routes as well as protocols to collect blood, to visualize sweat gland function, and to prepare skulls in mice.