Sweating ability of patients with p63-associated syndromes.

Sweating deficiency has been reported to represent a cardinal symptom of ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome and ankyloblepharon-ectodermal dysplasia-cleft lip/palate syndrome, two rare p63-associated disorders. According to online resources, hypohidrosis may lead to most life-threatening complications in affected patients. Thus, counseling on the prevention of hyperthermia would be indispensable in case of such syndromes, although detailed information on this issue is missing in the literature. We investigated 14 individuals with ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome (age range 2-48 years) and 9 individuals with ankyloblepharon-ectodermal dysplasia-cleft lip/palate syndrome (0.5-60 years of age) by confocal laser scanning microscopy to determine their palmar sweat duct density and by quantification of pilocarpine-induced sweating. Genotype-phenotype correlations were assessed. In 12 of 23 patients (52%), a normal amount of sweat ducts was detected. These individuals (9 with ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome, 3 with ankyloblepharon-ectodermal dysplasia-cleft lip/palate syndrome) produced sufficient sweat volumes (≥ 20 µl) in response to pilocarpine. All other patients had clearly reduced sweating ability and fewer sweat glands, but no anhidrosis. Alteration of a specific proline residue (Pro590) of p63 was consistently linked to impaired perspiration.Conclusion: Hypohidrosis in p63-associated syndromes is less common and potentially less severe than previously thought and may be attributable to certain genotypes. What is Known: • Hypohidrosis which has been listed as a cardinal symptom of AEC and EEC syndromes may lead to life-threatening hyperthermia. What is New: • Patients with EEC and AEC syndromes often can sweat normally. • Hypohidrosis seems to be attributed to certain TP63 genotypes.

Prenatal Correction of X-Linked Hypohidrotic Ectodermal Dysplasia.

Genetic deficiency of ectodysplasin A (EDA) causes X-linked hypohidrotic ectodermal dysplasia (XLHED), in which the development of sweat glands is irreversibly impaired, an condition that can lead to life-threatening hyperthermia. We observed normal development of mouse fetuses with Eda mutations after they had been exposed in utero to a recombinant protein that includes the receptor-binding domain of EDA. We administered this protein intraamniotically to two affected human twins at gestational weeks 26 and 31 and to a single affected human fetus at gestational week 26; the infants, born in week 33 (twins) and week 39 (singleton), were able to sweat normally, and XLHED-related illness had not developed by 14 to 22 months of age. (Funded by Edimer Pharmaceuticals and others.).

Two patients with localised hyperhidrosis of the hand based on functional and structural abnormalities of sweat glands.

A 14-year-old girl and a 30-year-old woman presented with localised hyperhidrosis on the dorsal hand and wrist, respectively, provoked by different stimuli such as physical activity and minor trauma to the skin. The skin was seemingly normal in both patients where an iodine-starch test revealed a well-demarcated area of hyperhidrosis. Following histopathological examination, the diagnosis was unilateral localised hyperhidrosis in both cases; one with normal histology and one with a nevus sudoriferous. Both patients were successfully treated with botulinum toxin type A. The 30-year-old woman additionally used low-dose propantheline bromide periodically and experienced long-term remission on this therapy. Hyperhidrosis may embarrass and interfere with patients' school and careers, and it is therefore important to tailor an effective individual treatment.

Atopic diathesis in hypohidrotic/anhidrotic ectodermal dysplasia.

Recently, patients with hypohidrotic/anhidrotic ectodermal dysplasia (H/AED) have been reported to have a higher prevalence of symptoms suggestive of atopic disorders than the general population. To better understand atopic diathesis in H/AED, 6 cases of clinically or genetically diagnosed H/AED were examined. The following criteria were evaluated with patient consent: sweating, blood test results, histopathology and filaggrin staining. Five of 6 H/AED cases displayed atopic dermatitis-like manifestations, and 3 of these 5 cases experienced periorbital lesions. H/AED patients tended to present with atopic dermatitis-like eruptions with characteristics potentially indicative of periorbital lesions. Atopic diathesis in H/AED appeared not to be associated with filaggrin. We could speculate that hypohidrosis or anhidrosis itself might impair skin barrier function and contribute to atopic diathesis.

Polipose palpebral por hidrocistoma écrino / Eyelid polyposis caused by eccrine hidrocystoma

Os hidrocistomas écrinos são lesões raras, císticas e benignas, que resultam em deformidades nas regiões palpebrais bilateralmente. Vários tratamentos são citados na literatura, porém nenhum deles é considerado padrão de referência. Deve-se somar as impressões obtidas à avaliação clínica e aos recursos disponíveis. Paciente de 73 anos, feminino, apresentando tumorações em regiões palpebrais bilaterais, de crescimento lento, com obstrução parcial do campo de visão e ectrópio. Foi submetida a dois procedimentos cirúrgicos para ressecção, em 2007 e em 2008. Apresentou melhora significativa do contorno palpebral bilateral, com boa simetria entre as regiões. O exame histopatológico concluiu: hidrocistoma écrino. O tratamento cirúrgico para a polipose palpebral bilateral relacionada ao hidrocistoma écrino mostrou-se uma modalidade que pode apresentar bons resultados estéticos e funcionais, sendo reprodutível, e sem causar maiores morbidades pós-operatórias ao paciente.

Eccrine hidrocystomas are rare lesions, cysts, or benign tumors, which lead to bilateral deformities in the eyelid areas. Several treatments are described in the literature. However, none of them has been established as the gold standard. Hence, it becomes necessary to consider the contribution of different opinions and available resources to clinical evaluation. A 73-year-old female patient presented with slow-growing tumors on both eyelids, which consequently led to partial visual field obstruction and ectropion. She underwent 2 surgical resections, one in 2007 and the other in 2008. As a result, she showed significant improvement of the bilateral eyelid contours and satisfactory symmetry between the areas. Histopathological diagnosis indicated eccrine hidrocystoma. The surgical treatment of bilateral eyelid polyposis associated with eccrine hidrocystoma proved to be a reproducible procedure that may ensure satisfactory aesthetic and functional results, without causing major postoperative morbidities to the patient.

Dermatoscopy as an adjunctive diagnostic tool in aquagenic syringeal acrokeratoderma.

Aquagenic syringeal acrokeratoderma (ASA) is a rare skin disorder of the palms and/or soles, characterized by whitish papules with occasional pruritus or pain sensation. Herein we report a 27-year-old man with a diagnosis of ASA based on clinical and histopathological features, and describe the dermatoscopic features consistent with threefold enlarged sweat duct pores compared with a normal-looking palmar skin area. As far as we are aware, dermatoscopic features of ASA have not been reported so far.

Hypohidrotic (anhidrotic) ectodermal dysplasia in female twins.

Autosomal recessive hereditary ectodermal dysplasia (HED) has not been described in sub-Saharan Africa. It is acknowledged to be rarer than the occasionally reported x-linked and autosomal dominant variants. We report a pair of Nigerian female twins with family history and clinical features suggestive of recessive HED, thereby showing the existence of this rare form in sub-Saharan Africa.

Prevalencia de signos de neuropatía diabética en una muestra de diabéticos tipo 2 del Área Sanitaria de Ferrol / Prevalencia of diabetic neuropathy signs in a simple of type 2 diabetics from the Health Area of Ferrol

Las actuales cifras hablan de costes millonarios para el tratamiento de las complicaciones de la Diabetes Mellitus (DM). Concretamente, la Asociación Americana de Diabetes (ADA) estima que en 2007 los costes directos e indirectos derivados de la DM en EE.UU ascendieron a 174 billones de dólares. De entre los factores de riesgo identificados por la ADA implicados en el desarrollo del pie diabético la neuropatía diabética periférica (NDP) se ha revelado como una afección de difícil diagnostico debido en gran parte a la escasez de sintomatología con que se presenta. Este hecho sumado a la poca atención que generalmente se le presta en la exploración clínica dificulta su pronta identificación y en consecuencia retrasa el tratamiento y la modificación de hábitos que eviten a largo plazo complicaciones mayores. Por estos motivos son cada Vez mas necesarias nuevas herramientas de diagnóstico precoz que puedan ser empleadas ambulatoriamente en la consulta. En el presente trabajo los autores han identificado signos de neuropatía diabética (componente sensitivo y autónomo) en una muestra de 181 diabéticos tipo 2 según criterios de la ADA de 2004 pertenecientes al Área Sanitaria de Ferrol empleando el diapasón graduado Rydel Seiffer y un nuevo test Visual (Neuropad®) de Valoración de la función sudoral del pie. Además se ha evaluado la presencia de tres factores de riesgo cardiovascular asociados a la diabetes mellitus tales como hipertensión arterial, hipertrigliceridemia y un índice tobillo-brazo patológico. La prevalencia de déficit de sensibilidad vibratoria utilizando el diapasón graduado Rydel Seiffer fue del 79%, en tanto que mediante el test Neuropad® las cifras de prevalencia de disfunción sudoral compatible con la afectación periférica del sistema nervioso autónomo fut: del 64,6%. En el total de la muestra se ha hallado una elevada prevalencia de factores de riesgo cardiovascular asociados a la diabetes mellitus: hipertensión arterial (60,7%), hipertrigliceridemia (57,4%) e índice tobillo-brazo patológico (68,5%) (AU)

It is actually estimated that diabetic complications have millionaire costs. The American Diabetes Association believes that in 2007 direct and indirect costs of Diabetes Mellitus were about 174 billion dollars in the U.S. One of the risk factors identified by the ADA involved in the development of the diabetic foot syndrome is diabetic neuropathy. Its complex diagnosis is due in part to the very few symptoms displayed and because of the little attention payed in the clinical examination. All these factors difficult its early diagnosis and in consequence setting up an appropriate treatment and a new healthy lifestyle avoiding long-term complications. For these reasons new simple, inexpensive, ambulatory diagnostic tools are necessary. In this cross-sectional study the authors have identified diabetic neuropathic signs (sensory and autonomic signs) using the graduated Rydel-Seiffer tuning fork and a new visual test (Neuropad®) based on the assessment of the foot sweat glands function in 181 type 2 diabetic patients (according to ADA criteria). Furthermore, prevalence of three cardiovascular risk factors was evaluated: arterial hypertension, hypertriglyceridemia and a pathological ankle brachial index. Prevalence of neuropathic signs using the graduated Rydel-Seiffer tuning fork was 79%. In contrast, using Neuropad® test the prevalence of sudomotor dysfunction compatible with peripherical affection of the autonomic nervous system was 64,6%. In the whole sample, we have found a high prevalence of cardiovascular risk factors associated with Diabetes Mellitus: 60,7% prevalence of arterial hypertension, S7,4% prevalence of hypertriglyceridemia and a 68,5% prevalence of pathological ankle brachial index (AU)

Sweating ability and genotype in individuals with X-linked hypohidrotic ectodermal dysplasia.

BACKGROUND: X-linked hypohidrotic ectodermal dysplasia (XLHED), the most common type of ectodermal dysplasia, is caused by EDA gene mutations. Reduced sweating contributes substantially to XLHED associated morbidity and mortality. To characterise the genotype-phenotype relationship, sweat gland function was assessed non-invasively in XLHED patients and healthy controls. SUBJECTS AND METHODS: In 36 genotyped XLHED patients and 29 control subjects aged 0-57 years, pilocarpine-induced sweat volume, palmar sweat pore density, and palmar skin conductance before and after stimulation were determined. RESULTS: Among 31 XLHED males, 14 had neither detectable sweat pores nor inducible sweating, 10 showed a few sweat pores but absent sweating, and 7 produced reduced sweat volumes (1-11 µl) as compared with controls (38-93 µl). Two of the low sweating XLHED subjects had normal sweat pore counts. In all 5 heterozygous females, some sweat was detected, but generally less than in female controls. Basal and stimulated skin conductance readings were reduced in 23 of 24 non-sweating, but only in 3 of 12 low-sweating XLHED subjects. There was no correlation between sweat production and number of missing teeth. CONCLUSIONS: In contrast to prior reports on non-genotyped hypohidrotic ectodermal dysplasia populations, this study confirmed a consistent, quantifiable defect of sweat gland function in male XLHED subjects as a disease biomarker. Among 26 different EDA genotypes, specific mutations were shown to be consistently associated with anhidrosis, implying that systematic mapping of EDA mutations together with the analysis of objective clinical data may help to distinguish functionally crucial mutations from those allowing residual activity of the gene product.

A novel 22-bp deletion mutation in a Chinese family with X-linked hypohidrotic ectodermal dysplasia.

X-linked hypohidrotic ectodermal dysplasia (XLHED) is the most common form of the ectodermal dysplasias characterized by an abnormal development of eccrine sweat glands, hair and teeth. Pathogenic mutations in the ED1 gene have been identified. In this family, a 22-bp deletion mutation of exon 8 in the ED1 gene was found in the affected members but not in the healthy individuals and 100 unrelated controls. We add new variant to the knowledge of ED1 mutations in XLHED.

Hypohidrotic ectodermal dysplasia and intrathoracic neuroblastoma.

We report a 6-year-old girl with a subtle form of hypohidrotic ectodermal dysplasia and a phenotype consisting of curly hair, a round face, a stocky build, and obesity, which was associated with intrathoracic neuroblastoma. Although this new association could be a chance occurrence, its description may alert physicians to look for similar combinations and report these, as it may lead to better syndrome delineation, and patient care.

Global developmental delay, osteopenia and ectodermal defect: a new syndrome.

UNLABELLED: Global developmental delay is a serious social problem. It is often unrecognized and the phenotypes are inadequately studied. To investigate the phenotypes of children with aspecific central nervous system (CNS) impairment (poor speech, maladaptive behavioral symptoms such as temper tantrums, aggressiveness, poor concentration and attention, impulsiveness, and mental retardation). SETTING: Tertiary care hospital. PATIENTS: Three children (two male siblings, and one unrelated girl). METHODS: We used the results from clinical neurological evaluations; imaging and electrodiagnostic studies; metabolic and genetic tests; skin biopsies and bone mineral densitometry. All three children suffered from (A) global developmental delay, (B) osteopenia, and (C) identical skin defects. The skin ultrastructural abnormalities were abnormal keratin differentiation, consisting of hyperkeratosis and granular layer thickening; sweat gland abnormalities, consisting of focal, cytoplasmic clear changes in eccrine secretory cells; and melanocyte abnormalities, with both morphological changes (reduced number and size without evident dendritic processes), and functional changes (defects in the migration of melanosomes in the keratinocytes). These patients present a previously unrecognized syndrome. We retain useful to report this new association, to be recognized, in the next future, as a specific key-sign of a well-defined genetic defect.

Síndrome de rapp hodgkin: a propósito de un caso: Centro de Recuperación Nutricional "Dr. Pastor Oropeza" San Cristóbal Estado Táchira-Venezuela noviembre 2003 / Rapp-Hodgkin syndrome: a purpose of a case: Centro de Recuperación Nutricional Dr. Pastor Oropeza San Cristóbal stado Táchira-Venezuela november 2003

La displasia ectodérmica hereditaria (DEH), representa un grupo de disturbios caracterizados por aplasia o displasia de estructuras y tejidos derivados del ectodermo. Las estructuras generalmente afectadas incluyen el cabello, piel, uñas, dientes y diversas glándulas. Esta condición representa un disturbio raro y se estima su frecuencia de un caso a cada 10.000 ó 100.000 nacimientos. La detección de la DEH en recién nacidos y en los primeros años de la infancia puede ser tarea difícil, debido a pocos cabellos y pelos, así como la ausencia de dientes, son características muy comunes durante esos períodos. Después de los primeros años de vida el diagnóstico es realizado con mayor facilidad, basados en la historia clínica del paciente y el examen físico. Es importante resaltar que en muchas circunstancias la DEH puede presentar características semejantes o hasta estar asociada a otros síndromes, tales como a ectocractilia displasia ectodérmica (EEC), síndrome trico-rino-falangeral y enfermedad de Robinson. El tratamiento de la DEH es exitosa cuando se establece el diagnóstico en el período adecuado o sea en la infancia. Un control multidisciplinario, instituido en los primeros años de vida del paciente, puede minimizar las posibles complicaciones odontológicas y médicas.

Manifestaciones ORL de la displasia ectodérmica hipohidrótica / ENT expression of hypohidrotic ectodermal dysplasia

La Displasia Ectodérmica Hipohidrótica (DEH) esuna rara enfermedad genética recesiva ligada al cromosoma X, que se caracteriza porque produce la afectación de estructuras derivadas principalmente del ectodermo, como piel y anejos (pelo y uñas), aunque tejidos no-ectodérmicos también pueden verse comprometidos. El cuadro clínico está dominado por la disminución del número de glándulas sudoríparas y sus más inmediatas consecuencias, escasa sudoración y aumento de la temperatura corporal. Las manifestaciones otorrinolaringológicas derivan de la hipoplasia de las glándulas mucosas del tracto aerodigestivo superior, y destacan por la frecuencia de presentación las infecciones crónicas, como rinitis, faringitis y otitis, y también epistaxis, disfagia, anodontia y ocena, entre otras. Se presenta el caso clínico de un paciente varón joven con DEH que se remite al Servicio de Otorrinolaringología con clínica de faringitis crónica y ocena, y a propósito del cual se revisa la bibliografía

Hypohidrotic Ectodermal Dysplasia (HED) is a rare recesive genetic disease linked to chromosome X whose main characteristic is the reduction of sweat glands, leadingto a deficient sweating and an increase in body temperature. In HED mainly the ectodermal structures are involved such, as epidermis and its anexes (hair and nails), although non ectodermal tissue may also become involved. Otolaryngological manifestations are related to hypoplasia of the mucousglands of the upper aerodigestive tract, as chronic infections, like rhinitis, pharyngitis, bronchitis and otitis, and also epistaxis, dysphagia, anodontia and, ozena, among others. A case of a young adult male affected with HED who is referred to the Otolaryngology Departament with a history of chronic pharyngitis and ozena, is presented and the literature reviewed

The Str mouse as a model for incontinentia pigmenti.

Striated mouse has been proposed as a model for incontinentia pigmenti (IP) based on the similarities in genetic predisposition and syntenic gene localisation in mouse. IP is considered an ectodermal dysplasia with all four characteristic structures involved: sweat glands, hair, teeth and nails. Recently mutations have been found in the Nsdhl, encoding an NAD(P)H steroid dehydrogenase-like protein in Str and Bpa mice. We analysed the phenotype of the Str mouse to evaluate the involvement of ectodermally derived tissues. Our results demonstrated that in Str mouse in addition to abnormal coat texture, sweat glands were severely dystrophic or missing. Retinal degeneration and skeletal abnormalities were also found. We conclude that Str mouse is a good model to get new insights in the pathogenesis of ectodermal dysplasias and X linked male lethality in humans.

Asombroso: dos pacientes que sudan sangre por la piel / Amazing: two patients that sweat blood through their skin

Antecedentes: Jesús, en el huerto de Getsemaní, poco antes de entrar en su pasión, según relatan los evangelistas "su sudor se convirtió en gruesas gotas de sangre que caían hasta el suelo. Además de este caso, solamente dos casos mas hemos encontrado reportados en la literatura médica mundial. Materiales: Paciente femenina de 22 años de edad, raza blanca, natural y residente en el paraje Soledad, Moca, Prov. Espaillat, R.D. y su hijo varón de tres años de edad, en quienes se reportan sudoración de sangre en mas de una oportunidad, Conclusión: se trata sin lugar a dudas de casos de hematohidrosis, algo excepcional reportado, posiblemente por primera vez en la República Dominicana

Sympathetic axons pathfind successfully in the absence of target.

To determine whether sympathetic axons require the presence of a peripheral target to grow to the correct destination, we examined the developing footpad innervation in tabby mutant mice which lack sweat glands. Despite the absence of sweat glands, noradrenergic sympathetic axons are transiently present in the presumptive target area and avoid the more distal epidermal/dermal domain occupied by sensory axons. Since sympathetic axon pathfinding was not dependent upon the target tissue, we compared the subsequent development of sweat gland axons in tabby footpads with that in control footpads. In wild-type mice, the gland-associated axonal plexus expands considerably as the secretory tubule enlarges and coils. This expansion, however, does not occur in tabby mice. The sweat gland innervation of wild-type mice loses catecholamines and acquires AChE activity and vasoactive intestinal peptide immunoreactivity. In tabby mutant mice, catecholaminergic fibers remain in the glandless footpads for 2 weeks and fail to acquire AChE or vasoactive intestinal peptide. In contrast to the altered development of gland innervation in tabby, the development of the innervation of footpad blood vessels was unaffected. Our observations indicate that the target is not required to direct sympathetic axons to the presumptive gland region of the footpad. In the absence of the target tissue, however, gland-targeted sympathetic axons retain an immature morphology and transmitter phenotype and then disappear.