Hypohydrotic Ectodermal Dysplasia in an Indian Family.

Hereditary ectodermal dysplasia (HED) is a rare genetic disorder chiefly affecting ectodermally derived structures including hair, nails, sweat glands etc. with pathognomic manifestations such as hypotrichosis, hypohidrosis, and hypodontia. Hypohidrotic ectodermal dysplaisa, being the most frequently encountered subtype and HED, being the rare subtype. HED is primarily transmitted through X-linked recessive trait in which the gene is carried by the female and manifested in male. Although rare, this disorder may be seen affecting lot of members of the same family. We hereby report a series of four cases with common classical manifestations accompanied with spoon shaped nails, hyperpigmentation, oligodontia and hypotrichosis. The patients were treated for prosthetic rehabilitation and were asked to wear cool clothing.

Variants of the ectodysplasin A1 receptor gene underlying homozygous cases of autosomal recessive hypohidrotic ectodermal dysplasia.

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.

Conservation analysis and pathogenicity prediction of mutant genes of ectodysplasin a.

BACKGROUND: Hypohidrotic ectodermal dysplasia (HED) is a common recessive X-linked hereditary disease that affects the development of ectoderm. Gene mutations of ectodysplasin A (EDA) play key roles in process of this disease. In our preliminary study, three unknown mutation sites (c.878 T > G, c.663-697del and c.587-615del) were detected from the pedigrees of HED. METHODS: Conservation analysis of the related homologous proteins in 3 unknown EDA gene mutation sites was conducted using the University of California Santa Cruz (UCSC) Genome Browser database. SIFT and PolyPhen-2, the online gene function prediction software, were utilized to predict the pathogenicity of point mutation of c.878 T > G. RESULTS: All three unknown mutation sites were located in the highly-conserved region of EDA and possessed strong amino acid conservation among different species. In addition, the results of the pathogenicity prediction of point mutation of c.878 T > G by SIFT (P = 0.00) and PolyPhen-2 (S = 0.997) demonstrated that the mutation site had considerable pathogenicity theoretically. CONCLUSIONS: The EDA mutations of c.878 T > G, c.663-697del and c.587-615del may be responsible for the pathogenesis of HED in their pedigrees.

A novel mutation in the EDAR gene causes severe autosomal recessive hypohidrotic ectodermal dysplasia.

We report on a 2-year-old girl presenting with a severe form of hypohidrotic ectodermal dysplasia (HED). The patient presented with hypotrichosis, anodontia, hypohidrosis, frontal bossing, prominent lips and ears, dry, pale skin, and dermatitis. The patient had chronic rhinitis with malodorous nasal discharge. The girl was the second born child of first-cousin immigrants from Northern Iraq. A novel homozygous mutation (c.84delC) in the EDAR gene was identified. This mutation most likely causes a frameshift in the protein product (p.S29fs*74). This results in abolition of all ectodysplasin-mediated NF-kB signalling. This complete loss-of-function mutation likely accounts for the severe clinical abnormalities in ectodermal structures in the described patient.

Displasia ectodérmica hipohidrótica: Reporte de casos / Hypohydrotic ectodermal dysplasia: Report of cases

La Displasia Ectodérmica Hipohidrótica (DEH) es una genodermatosis que se caracteriza por presentar alteraciones en las estructuras derivadas del ectodermo y frecuentemente se da la triada: hipohidrosis, hipotricosis e hipodoncia. El síndrome puede manifestarse como herencia autosómica dominante o recesiva y también como herencia ligada al sexo. El objetivo de este artículo es presentar 6 casos clínicos atendidos en la clínica del Niño de la Facultad de odontología de la Universidad de Antioquia, entre 1998 y 2011. Se muestran las características faciales y dentales de una familia con displasia ectodérmica hipohidrótica con herencia ligada al cromosoma X. Para el tratamiento de este síndrome se propone un protocolo de manejo en forma integral y multidisciplinario (AU)

Ectodermal Hypohidrotic Dysplasia (EHD) is a genodermatosis characterized by the presence of the ectoderm-derived structures alterations and often the triad is given: Hypohidrosis, Hypotrichosis and hypodontia. The purpose of this article is to present 6 clinic cases attended in the Clinic of the Children Dental Care of the Faculty of dentistry of the University of Antioquia between 1998 and 2011. It´s document the oral and facial characteristics in this pathology in a family with inheritance associated with the X chromosome. For the treatment of this syndrome a protocol of management in multidisciplinary and integral form is proposed (AU)

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

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

A compound heterozygous mutation in the EDAR gene in a Spanish family with autosomal recessive hypohidrotic ectodermal dysplasia.

Hypohidrotic ectodermal dysplasia (HED) is a genetic disorder characterised by sparse hair, lack of sweat glands and malformation of teeth. The X-linked form of the disease, caused by mutations in the EDA gene, represents the majority of HED cases. Autosomal forms result from mutations in either the EDAR or the EDARADD gene. The X-linked and autosomal forms are phenotypically indistinguishable. For the purpose of genetic counselling, it is, therefore, important to know which gene is involved. In this study, we ascertained a Spanish family demonstrating the autosomal recessive form of HED. Affected individuals in the family showed the characteristic features of HED, including fine and sparse scalp hair, sparse eyebrows and eyelashes, periorbital hyperpigmentation, prominent lips, hypodontia and conical teeth, reduced sweating, and dry and thin skin. Sequence analysis of the EDAR gene revealed a novel compound heterozygous mutation [c.52-2A>G; c.212G>A (p.Cys71Tyr)]. Our finding extends the body of evidence that supports the significance of the EDAR signalling pathway in the ectodermal morphogenesis.

Hypohidrotic ectodermal dysplasia with atrophic rhinitis and nasal myiasis.

Hypohidrotic/anhidrotic ectodermal dysplasia is a rare inherited disorder characterized by hypohidrosis/anhidrosis, hypotrichosis, dysodontia and heat intolerance. Most common mode of transmission is X-linked recessive, showing complete expression in males, and only partial manifestations in the female carrier heterozygotes. Features like atrophic rhinitis, nasal and aural myiasis, syndactyly, cleft lip and/or palate, mental retardation and immunodeficiency are uncommonly seen in this syndrome. We hereby report a case of hypohidrotic ectodermal dysplasia with unusual features of atrophic rhinitis and nasal myiasis.

[Anhidrotic/hypohidrotic ectodermal dysplasia: ten cases]. / Dysplasie ectodermique hypo/anhidrotique: 10 observations.

BACKGROUND: Ectodermal dysplasias are rare hereditary diseases characterised by congenital absence of ectodermally derived structures and classified according to four symptoms: trichodysplasia, hypodontia, onychodysplasia and hypohidrosis. AIM: The objective of our study is to precise the epidemioclinical characteristics, the diagnostic tools, the evolution and the treatments of this rare disease through a 10-case series of hypohidrotic ectodermal dysplasia (HED). METHODS: The present report is a retrospective study of all cases of an/hypohidrotic ectodermal dysplasia collected from 1977 to 2006. We have specified age, sex, parental consanguinity, similar familial cases, clinical and histological features, dental, oto-rhino-laryngologic, ophthalmologic and respiratory examinations. RESULTS: Ten cases of HED were collected (average age: 14 years, sex ratio 9/1). The mean duration diagnostic period was of 14 years. Parental consanguinity was registered in 3 cases but only one patient had similar familial cases. All patients had facial dysmorphy, hypotrichosis and hypo/anodontia (respectively 8/10 and 2/10). All patients had clinically and histologically documented hypoplastic (6/10) or aplastic sweat glands (4/10). Extra-cutaneous manifestations were noted in 8 patients (recurrent rhinitis 6/10, recurrent pneumopathies 3/10, xerophtalmy 3/10). CONCLUSION: Our series deals with 10 cases of HED, consisting in Chris-Siemens Touraine syndrome. It highlights the delayed diagnosis of this disease (mean: 14 years) with a diagnosis made at an adult age in four patients. Our study confirm the X-linked heredity (9/10) with a possible autosomal transmission (one female-case). HED is rarely life-threatening, but early diagnosis allows a better quality of life to patients and genetic counselling to parents. Our series illustrates the rarity of HED which is also probably due to its underestimation by clinicians.

Unusual presentation of a severe autosomal recessive anhydrotic ectodermal dysplasia with a novel mutation in the EDAR gene.

We report on an 18-year-old woman, born to first-cousin parents, presenting with a severe form of anhydrotic ectodermal dysplasia (EDA/HED). She had sparse hair, absent limb hair, absent sweating, episodes of hyperpyrexia, important hypodontia, and hyperconvex nails. She also showed unusual clinical manifestations such as an absence of breasts, a rudimentary extranumerary areola and nipple on the left side, and marked palmo-plantar hyperkeratosis. Light microscopy of skin biopsies showed orthokeratotic hyperkeratosis and absence of sweat glands. A novel homozygous mutation (IVS9 + 1G > A) in the EDAR gene was identified. This mutation results in a total absence of EDAR transcripts and consequently of the EDAR protein, which likely results in abolition of all ectodysplasin-mediated NF-kappaB signaling. This is the first complete loss-of-function mutation in the EDAR gene reported to date, which may explain the unusual presentation of HED in this patient, enlarging the clinical spectrum linked to the dysfunction of the ectodysplasin mediated NF-kappaB signaling.

Hypohiderotic ectodermal dysplasia.

We report a case of a six years age girl who presented to our out patients department with the history and findings suggestive of recurrent respiratory tract infections. She was also noticed to have: non homogeneous hyperpigmented patches on the face since three months of age, sparse hair on the scalp and eyebrows, conical peg like teeth and delayed dentition, prominent and low set ears, perpetually flexed third toe bilaterally. Axillary skin biopsy showed adenexal structures and eccrine glands in subcutaneous fat which were reduced in number. The diagnosis made was: Anhydrotic/Hypohidrotic type of ectodermal dysplasia.

Dysplasia ectodérmica hipohidrótica: causa inusual de fiebre de origen desconocido / No disponible

La displasia ectodérmica hipohidrótica (DEH) es una patología que debe considerarse dentro del diagnóstico diferencial de los procesos febriles en la infancia, sobre todo sin son recurrentes o de origen desconocido. Se presenta un nuevo caso de DEH en un lactante varón de 13 meses con cuadro febriles de repetición sin foco y con el fenotipo característico, consistente en un pelo ralo y escaso, hipodoncia, piel fina y seca y una facies peculiar. El conocimiento de las características clínicas tan específicas de esta entidad nos puede permitir un diagnóstico precoz y relativamente sencillo, minimizando así la iatrogenia asociada a la demora diagnostica (AU)

Hypohidrotic ectodermal displasia (HED( is a pathology that must be considered in the differential diagnosis of childhood´s febril processes, mainly if they are recurrent or of unknown origin. We present here a new case of HED in a 13 months old boy with recurrent fevers without focus, exhibiting a particular phenotype consisting of fine and scarce hair, oligodontia, smooth and dry skin and a particular facies. The knowledge of these particular clinical features allow an early and relative simple diagnosis, minimizing the iatrogenia associated to delays in diagnosis (AU)