Ectodermal Dysplasia Syndrome Research Articles

Ectodermal dysplasia (ED) syndrome

Ectodermal dysplasia (ED) syndrome

Genotypic and phenotypic correlations in tooth agenesis: insights from WNT10A and EDA mutations in syndromic and non-syndromic forms.

Tooth agenesis (TA) occurs when tooth development is disrupted at the initiation stage. It can be classified into non-syndromic and syndromic forms (named NSTA and STA), depending on whether it is accompanied by abnormalities of other organs and systems. Genetic factors play a predominant role in the pathogenesis of tooth agenesis, with dozens of genes implicated in both forms. Several genes have been identified, mutations in which can lead to both forms of TA. Among these, WNT10A and EDA are frequently mutated genes in this context, representing extensively researched and documented genes in human non-syndromic selective agenesis of permanent teeth and their association with ectodermal dysplasia syndromes. In this review, we present an overview of the current knowledge regarding genes associated with NSTA and STA, focusing on the distribution and nature of WNT10A and EDA gene mutations. We also explore how these mutations relate to the condition's both forms, including their association with the number of missing permanent teeth.

Prevalence rates for ectodermal dysplasia syndromes.

Ectodermal dysplasias (EDs) are a heterogeneous group of genetic conditions affecting the development and/or homeostasis of two or more ectodermal derivatives, including hair, teeth, nails, and certain glands. There are currently 49 recognized EDs with molecularly confirmed etiology. The EDs are very rare disorders, individually and in aggregate. Very little is published regarding the prevalence of these rare disorders. As a result of the genomics revolution, rare diseases have emerged as a global health priority. The various disabilities arising from rare disorders, as well as diagnostic and treatment uncertainty, have been demonstrated to have detrimental effects on the health, psychosocial, and economic aspects of families affected by rare disorders. Contemporary research methodologies and databases can address what have been historic challenges encountered when conducting research on rare diseases. In this study, we aim to ascertain period prevalence rates for several of the more common ectodermal dysplasia syndromes, by querying a large multicenter database of electronic health records, Oracle Real-World Data. For each of the included ectodermal dysplasia syndromes a clinical definition was developed by a committee of international experts with interests in EDs. The clinical definitions were based upon a combination of clinical features and designated by ICD-9 and ICD-10 codes. The January 2023 version of the Oracle Real-World Data database was queried for medical records that coincided with the clinical definitions. For our study, there were 64,523,460 individual medical records queried. Period prevalence rates were calculated for the following ED disorders: hypohidrotic ectodermal dysplasia, found to be 2.99 per 100,000; ectodermal dysplasia and immunodeficiency 1, 0.23 per 100,000; Clouston syndrome, 0.15 per 100,000; ectrodactyly ectodermal dysplasia and cleft lip/palate syndrome, 0.61 per 100,000; ankyloblepharon-ectodermal defects-cleft lip/palate syndrome, 0.36 per 100,000; focal dermal hypoplasia, 0.10 per 100,000; and incontinentia pigmenti, 0.88 per 100,000. This study established estimated period prevalence rates for several of the ectodermal dysplasia syndromes, and it demonstrated the feasibility of utilizing large multicenter databases of electronic health records, such as Oracle Real World Data.

Punctal Atresia As a Clinical Indicator of Systemic Genetic Anomalies

ABSTRACT Background Punctal atresia or agenesis (PA) is a rare congenital anomaly characterized by the absence or closure of the tear duct puncta, potentially linked to systemic genetic anomalies. The necessity of a genetic workup based solely on the presence of PA remains uncertain. This study investigates a cohort of PA patients, examining the prevalence and types of associated syndromes. Methods A retrospective medical records review of all patients diagnosed with PA at the Children’s Hospital of Philadelphia between 2009–2023 was conducted, analyzing medical histories and genetic testing results. Primary outcomes included the prevalence of systemic syndromes, while secondary outcomes focused on the variety of associated syndromes. Results Forty-four patients were included, of which 31 were male (70%) with a mean ± SD age 3.3 ± 3.3 years. Overall, 87 puncta in the study cohort were affected, and 26 cases (59%) were bilateral. Systemic abnormalities or genetic syndromes were identified in 19 patients (43%), with the most common being Ectodermal Dysplasia and Down syndrome. Additional rare syndromes were demonstrated. No significant association was found between systemic abnormalities and gender, bilaterality, or the number of puncta involved. Conclusions A high incidence of systemic syndromes (43%) was observed in the study cohort. In individuals with PA who also exhibit extraocular disease, systemic evaluation and genetic workup should be considered. Syndromic diagnoses identified in our cohort also include: Branchio-oto-renal syndrome, 22q11.2 deletion syndrome, 1q21.1 microdeletion syndrome, NF1, monosomy 4q and trisomy 6q, which represent novel associations. The lack of correlation between PA’s phenotypic severity and systemic abnormalities highlights the need to obtain a comprehensive medical history and consider a systemic workup in PA patients.

Hereditary juvenile macular dystrophy: A series of three cases

Hereditary juvenile macular dystrophy (HJMD) is a rare autosomal recessive disorder caused by mutations in the CDH3 gene. The “ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome” (EEMS) is caused by the CDH3 mutation and is characterized by macular dystrophy, hypotrichosis, dysplastic nails, partial anodontia, and various limb defects. We present a series of three cases with HJMD. The important clinical features, ocular and systemic, and genetic tests performed are highlighted in our case series.

The new karyotypic alteration in a patient with cleft lip and palate-ectrodactyly and ectodermal dysplasia syndrome

The new karyotypic alteration in a patient with cleft lip and palate-ectrodactyly and ectodermal dysplasia syndrome

Report of TSPEAR Variants, the Hypereosinophilic Syndrome, and Severe Atopy

BackgroundBiallelic loss-of-function variants in the thrombospondintype laminin G domain and epilepsy-associated repeats (TSPEAR) gene have been associated with ectodermal dysplasia (ED), phenotypes that affect ectodermal-derived structures, including hair, skin, nails and tooth involvement, as well as hearing loss, specifically, sensorineural hearing loss. Historically, TSPEAR related disorders have been autosomal recessive. Other forms of ectodermal dysplasia including anhidrotic ectodermal dysplasia with immune deficiency (EDA-ID) have been associated with immune dysregulation, primary immunodeficiency, and atopy, including EoE, atopic dermatitis (AD), food allergy (FA), asthma, and allergic rhinitis (AR). The abnormal skin barrier and transepidermal allergen absorption has been proposed as a mechanism. We report the first known case of Hypereosinophilic Syndrome (HES) and severe atopy including eosinophilic esophagitis (EoE) associated with TSPEAR mutations.Case presentation: 5-year-old male with a history of FA, asthma, and AR who later developed HES, severe AD, and EoE. HES presented age 2-years, resolving with a course and taper of high dose prednisolone. Remarkable findings on HES evaluation included an absolute eosinophil count of 10,480, IgE of 2,566 IUnits/mL, and EoE with up to 60 eos/HPF in esophagus on EGD. He was multiply sensitized to environmental allergens. FISH analysis was normal with no evidence of FIP1L1/PDGFRA. Bone marrow biopsy was significant for a normocellular bone marrow with multilineage hematopoiesis and markedly increase in eosinophils. Genetics evaluation noted hypodontia, pointed teeth, and coarse hair. He was found on whole exome sequencing to have 2 variants of unknown significance (VUS) in TSPEAR gene, one from each parent. His presentation was felt to be feasibly related to the VUS but more information about the VUS was needed to provide molecular confirmation. ConclusionWe report the first known case of association of two VUS in the TSPEAR gene with immune dysregulation including HES and severe atopy (FA, asthma, AR, AD, and EoE). Epidermal abnormalities with TSPEAR mutations may be similar to other ED syndromes with regards to development of severe atopy and immune dysregulation, with transepidermal sensitization playing a role.

Congenital hand anomalies and rare syndromes in children

Congenital hand anomalies and associated rare syndromes in children are commonly seen in clinical practice and require complete clinical, radiological and genetic evaluation. The purpose of this case series is to describe four rare syndromic children with varied hand anomalies and differences. Three of the children are female and one is a male. Distal limb defects from simple polydactyly, clinodactyly to cleft hand were identified including preaxial anomalies. Significant clinical problems noted were chiefly cosmetic and altered self-image was also noted in one child. The orofacial clefting noted in the child with ectrodactyly ectodermal dysplasia (EEC) syndrome required repeated surgery though the child had minimal feeding difficulty and significant speech delay. Multidisciplinary management is necessary with the early involvement of clinical geneticist.

310 Metatranscriptomics detects emerging multidrug-resistant Candida auris in a family with a mild TP63-associated ectodermal dysplasia

Tumor protein 63, encoded by TP63, has an essential role in epidermal differentiation and ectodermal development. Autosomal dominant mutations in human TP63 result in several overlapping syndromes, with some established genotype-phenotype correlations based on the protein domain affected. Several groups have linked TP63-associated ectodermal dysplasia (ED) syndromes with varying degrees of immune dysfunction. In this study, we followed the clinical course of a daughter and father who presented with mild ED symptoms, chronic mucocutaneous candidiasis (CMC), recurrent bacterial infections, and equivocal immune function status.

493 Chronic mucocutaneous candidiasis due to Candida auris and non-albicans Candida species in a family with a mild TP63-associated ectodermal dysplasia

Tumor protein 63, encoded by TP63, has an essential role in epidermal differentiation and ectodermal development. Autosomal dominant mutations in human TP63 result in several overlapping syndromes, with some established genotype-phenotype correlations based on the protein domain affected. Several groups have linked TP63-associated ectodermal dysplasia (ED) syndromes with varying degrees of immune dysfunction. In this study, we followed the clinical course of a daughter and father who presented with mild ED symptoms, chronic mucocutaneous candidiasis (CMC), recurrent bacterial infections, and equivocal immune function status.

Major indications and current clinical findings of zygomatic implant: a systematic review

Introduction: The lack of bone in the alveolar crest represents a major problem in aesthetic recovery in patients who have suffered dentoalveolar trauma, traumatic extractions, congenital tooth absence pathologies involving maxilla and mandible, and the possibility of deformity. In this sense, the zygomatic implant (ZI) is an alternative when there is bone loss. Objective: It was to carry out a systematic review of the main clinical outcomes of ZI, emphasizing the main indications. Methods: The present study followed the PRISMA rules. The search strategy was performed in the PubMed, Scielo, Cochrane Library, Web of Science and Scopus, and Google Scholar databases, following the rules of the word PICOS (Patient; Intervention; Control; Outcomes; Study Design). The Cochrane Instrument was used to assess the risk of bias of the included studies. Results and Conclusion: A total of 82 articles were found involving zygomatic implantation and the evolution of the technique. Initially, the duplication of articles was excluded. A total of 54 articles were fully evaluated and 33 were included in this study. Based on the clinical results of the last five years, some studies have broadened clinical understanding based on comparative studies to show the success rate of ZI. Even if more complications were reported for ZI that resolved spontaneously or could be handled, ZI proved to be a better modality of rehabilitation for severely atrophic jaws. Furthermore, zygomatic surgery proved to be a viable and safe alternative to conventional treatment modalities for oral rehabilitation of patients with ectodermal dysplasia syndrome. Also, there was greater accuracy and drastically reduced risk of perioperative/postoperative complications using the dynamic navigation system compared to the freehand placement of implants. Finally, guided surgery for the placement of ZI using specially designed metal jigs that must be supported by bone showed the placement of a made-to-measure provisional prosthesis, reducing surgery time, simplifying the procedure, and optimizing the result.

324 Improvement of epidermal covering on AEC patients with severe skin erosions by PRIMA-1MET

P63 is a major transcription factor regulating skin development and homeostasis : cell proliferation, adhesion, and early differentiation. P63 is mutated in several rare syndromes called p63-related ectodermal dysplasia syndromes (ED). One of the main form, called AEC syndrome, associates ankyloblepharon, clef/lip palate, ED, and severe skin erosions that not always heal. P63 belongs to the p53 gene family. We found that ED-iPSC epidermal commitment can be rescued by a p53-reactivating compounds called PRIMA-1MET currently used in anticancer clinical trials.

Molecular basis of ectodermal dysplasia

Ectodermal dysplasia (ED) syndrome is a rare genetic disease that involves a heterogeneous group of hereditary disorders that occur as a result of mutations in genes that code for development of fetal ectoderm and lead to numerous disorders. Defects in the development of the ectoderm cause symptoms in tissues derived from the ectoderm layer, such as skin, nails, hair, and teeth. Because many pathways are involved in the development of the ectoderm, there are mutations in many genes that cause ED. Owing to the heterogeneity of ED, there are different types of the disease that have different symptoms. These symptoms include sparse hair, abnormal or missing teeth, nail dystrophy, lack of sweating owing to the absence of sweat glands, and cancer. In this review, in addition to discussing the role and pathway of each of the genes involved in ED, the incidence of cancer in these patients, diagnostic methods and differentiation from other similar diseases, and the treatments currently being performed for ED are discussed.

Scleral Perforation Secondary to Cyclophotocoagulation

A 66-year-old man with ectodermal dysplasia syndrome, right eye Type 1 Boston Keratoprosthesis (K-Pro), and chronic angle-closure glaucoma underwent cyclophotocoagulation diode in the right eye (2500 mW, 2-4 seconds), which resulted in scleral perforation with 3 Seidel positive holes along the inferotemporal limbus (Fig A). LiquiBand glue was applied and the perforations were covered with a Tutoplast scleral patch graft followed by amniotic membrane (Fig B). Two weeks later, the graft had fallen off (Fig C), and the large perforations coalesced.

Multimorbidity in Pediatric Dermatology: Clinical Case

Background. Nowadays, dermatoses with mixed clinical picture and resistant to classical management become more common. The presence of various genetic disorders typical for most chronic dermatoses may indicate possible combination of several nosologies.Clinical Case Description. The article presents the clinical case of multimorbid condition in 10 years old patient who has nucleotide variants in CARD14 and EXPH5 genes. Mutations in CARD14 gene are typical for patients with type 2 psoriasis and pityriasis rubra pilaris (autosomal dominant type), while mutations in EXPH5 gene are typical for patients with non-specific epidermolysis bullosa (autosomal recessive type). Mutation in the TGM1 gene that is described in patients with congenital ichthyosis (autosomal recessive type), pathogenic mutations in KRT74 gene typical for ectodermal dysplasia, hypotrichosis and uncombable hair syndrome, and mutations in the KRT86 gene typical for monilethrix were also revealed. Medical history taking and histological examination as well as clinical data evaluating are crucial for correct diagnosis. They allow to understand the absence of the such manifestations in relatives and reveal various pathological processes in the epidermis. Molecular genetic testing with new generation sequencing (NGS) helps to finally establish the diagnosis and determine the further tactics for patient management.Conclusion. Multidisciplinary approach and use of high-technology methods of examination and treatment (such as molecular genetic testing and biological therapy) are required for final diagnosis in severe forms of chronic dermatosis resistant to treatment and for decision on correct tactics for the further management of such patients.

Ectodermal Dysplasia: An Overview

Ectodermal dysplasia is a rare hereditary disorder with a characteristic physiognomy. It is a genetic disordermainly striking the growth or purpose of the teeth,hair, nails and sweat glands. Ectodermal dysplasia canalso affect the skin, the lens or retina of the eye, partsof the inner ear, the growth of fingers and toes, thenerves and other parts of the body providing to thes pecific syndrome. All the syndrome generallyinvolves adifferent combination of symptoms, which can range from mild to severe. The antiquity andlessons learnedfrom hypohidrotic ectodermaldysplasia (HED) can serve as an example for investigating the root andpathogenesis of other ectodermal dysplasia syndromes by denoting that phenotypically identical syndromescan be caused by mutations in different genes, mutations in the same gene can lead to different phenotypesand that mutations in the genes further ensue in the same indicating pathway may alter the phenotype quiteprofoundly. This paper aims to describe and discuss the etiology, genetic review, clinical manifestations andtreatment options of this hereditary disorder.

Cleft Lip and Palate in Ectodermal Dysplasia.

Ectodermal dysplasia (ED) comprises multiple syndromes that affect skin, hair, nails, and teeth, and sometimes are associated with orofacial clefting. The purpose of this study is to (1) identify the prevalence and characteristics of cleft lip and/or palate (CL/P) in patients with ED and (2) describe the management and outcomes. Retrospective review from 1990 to 2019. All patients with ED treated at Boston Children's Hospital. Prevalence of CL/P was calculated and clinical details recorded: phenotypic anomalies, cleft type, operative treatment, and results of repair. Of 170 patients with a purported diagnosis of ED, 24 (14%) had CL/P. Anatomic categories were bilateral CL/P (67%), unilateral CL/P (8%), and cleft palate only (25%). The most common ED syndrome (37%) was ectrodactyly, ectodermal dysplasia, and cleft lip/palate (EEC). Pathogenic variants in TP63 were the most frequent finding in the 11 patients who had genetic testing. Aberrations from a typical clinical course included failure of presurgical dentofacial orthopedics, dehiscence of nasolabial adhesion, and total palatal absence requiring free-flap construction. Two patients had prolonged postoperative admission for respiratory infection. High fistula (8%) and velopharyngeal insufficiency (33%) rates reflected the predominance of bilateral complete forms. As in other types of syndromic CL/P, cleft phenotypic expression in ED is more severe than the general cleft population. Further studies are needed to correlate genotype and phenotype for the distinct syndromes included in the ED spectrum.

Zygomatic implant survival in 9 ectodermal dysplasia patients with 3.5- to 7-year follow-up.

Ectodermal dysplasia syndrome is a complex group of genetic disorders identified by the abnormal development of the ectodermal structures. The aim of this retrospective clinical case series report was to evaluate the outcomes of the ectodermal dysplasia syndrome patients that underwent zygomatic implant surgery. A total of 9 ectodermal dysplasia syndrome patients aged between 21 and 56years (mean age 36.8) with severely atrophic maxilla were included in this study. All the patients were treated with a total of 19 zygomatic implants. The mean follow-up of the patients was 55months (with a range of 44-84months). The implant survival rate was evaluated as a primary outcome. The intra- and postoperative complications were evaluated as additional criteria for success. The overall implant survival rate was 100% without any complications. Final or provisional prosthesis was delivered on the same day of surgery, which resulted in an improvement of the quality of life of the patients. According to the results of this study, zygomatic surgery can be considered as a viable and safe alternative to conventional treatment modalities for oral rehabilitation of ectodermal dysplasia syndrome patients.

Clinico-etiological study of pediatric dermatoses in tertiary health care hospital in East-coast Andhra Pradesh, India

<p class="abstract"><strong>Background:</strong> Pediatric dermatoses vary vastly from adult dermatoses in clinical presentation, treatment and prognosis and are more influenced by socioeconomic status, climatic exposure, dietary habits, external environment, thereby needing a special view in this field. The present study was carried to determine the clinico-epidemiological patterns of pediatric dermatoses.</p><p class="abstract"><strong>Methods:</strong> Consecutive 2581 children aged >1 month to 12 years with 2661 dermatoses attending dermatology OPD in tertiary care hospital, Kakinada (May 2018 to June 2019) with clinical evidence of cutaneous disorder were studied. Complete history and cutaneous examination with necessary investigations are recorded.<strong></strong></p><p class="abstract"><strong>Results:</strong> Infestations disorder in 39.68% followed by eczematous disorder 19.80%, infection in 13.71%, pigmentary disorder in 8.34%, papulosquamous disorder in 5.82%, appendageal disorder in 2.93%, nutritional disorder in 2.21% and drug reactions including toxic epidermal necrolysis in 1.12%, child abuse and sexually transmitted diseases in 0.37% was the pattern in the present study. Rare cases including aplasia cutis, cutis laxa, ectodermal dysplasia, monilethrix and griscelli syndrome, epidermolysis bullosa, ichthyosis, palmoplantar keratoderma and congenital syphilis were also observed. The most common cutaneous dermatoses are infection and infestations followed by eczemas and nutritional disorders. Surprisingly STD and child abuse contributed significantly which cannot be neglected. Genodermatosis were notable in the study probably due to the high incidences of consanguineous marriage</p><p class="abstract"><strong>Conclusions:</strong> The study reinforces features of tropical paediatric dermatology especially high prevalence of infections and infestations in school children (5-12 years) which highlights the need of proper counselling of caretaker regarding skin hygiene and establishment of specialized paediatric dermatology clinics.</p>

ОСОБЕННОСТИ СЪЕМНОГО ЗУБНОГО ПРОТЕЗИРОВАНИЯ У ДЕТЕЙ И ПОДРОСТКОВ С ВРОЖДЕННОЙ АДЕНТИЕЙ И ЭКТОДЕРМАЛЬНОЙ ДИСПЛАЗИЕЙ

Subject. Congenital adentia in children and adolescents related ectodermal dysplasia is a rare pathology in dental practice. Scientific articles of this problemare some case reports. The theory and practice of overdenture tooth replacement in children has a number of identifying features on clinical management of patients. There is no information on this problemin the contemporary literature.
 Purpose ― improvement of efficiency of orthopedic treatment of children and adolescents with congenital adentia and ectodermal dysplasia on the basis of development of clinical guidelines on peculiarities of removable dental prosthesis in this category of patients.
 Methodology. The work is based on the 24 of orthopaedic rehabilitation for patients aged 3 to 12, with hypohydrotic ectodermal dysplasia syndrome and congenital adenia. Dental prosthetics were performed using removable structures. In terms of 6 months to 2.5 years, due to the growth of jaws, new prostheses were manufactured. Distant observation periods were up to 18 years.
 Results. The features of removable dental prosthesis in this category of patients, which are important and effective in practical activity, are formulated in the form of successive 18 basic postulates (initial provisions adopted without evidence), which are clinical guidelines for practical application and "Check list for care of removable dental prostheses and their use" for children and their parents.
 Conclusion. The developed clinical guidelines on practical aspects of the features of removable dental prosthesis in children with congenital adenatia and ectodermal dysplasia are an effective tool for increasing the effectiveness of orthopedic treatment of this category of patients. Compliance with these guidelines allows improving adaptation of children to removable orthopedic structures, reducing the number of complications, providing optimal conditions for growth and development of toothless areas of jaws, facial skeleton, in accordance with age-related physiological standard.