Characterization of X‐linked hypohidrotic ectodermal dysplasia (XL‐HED) hair and sweat gland phenotypes using phototrichogram analysis and live confocal imaging

Abstract

Hypohidrotic ectodermal dysplasia (HED) is the most common type of ectodermal dysplasia (ED), which encompasses a large group of syndromes that share several phenotypic features such as missing or malformed ectodermal structures, including skin, hair, sweat glands, and teeth. X-linked hypohidrotic ectodermal dysplasia (XL-HED) is associated with mutations in ectodysplasin (EDA1). Hypohidrosis due to hypoplastic sweat glands and thin, sparse hair are phenotypic features that significantly affect the daily lives of XL-HED individuals and therefore require systematic analysis. We sought to determine the quality of life of individuals with XL-HED and to quantify sweat duct and hair phenotypes using confocal imaging, pilocarpine iontophoresis, and phototrichogram analysis. Using these highly sensitive and non-invasive techniques, we demonstrated that 11/12 XL-HED individuals presented with a complete absence of sweat ducts and that none produced sweat. We determined that the thin hair phenotype observed in XL-HED was due to multiple factors, such as fewer terminal hairs with decreased thickness and slower growth rate, as well as fewer follicular units and fewer hairs per unit. The precise characterization of XL-HED phenotypes using sensitive and non-invasive techniques presented in our study will improve upon larger genotype-phenotype studies and in the assessment of future therapies in XL-HED.

The characterization of hypodontia, hypohidrosis, and hypotrichosis associated with X‐linked hypohidrotic ectodermal dysplasia: A systematic review

“…Of the eight males with sweat ducts, they all had reduced sweating volume, with a mean of 5.625 μl (range: 1–12 μl) compared to controls (range: 48–93 μl). Similarly, Jones et al () reported 12 individuals had no sweat ducts and subsequently no sweating ability. Schneider et al () reported that of 31 males, 45.2% had no sweat ducts (thus, zero sweat volume), 48.4% had reduced sweat ducts compared to controls and significantly low sweating volume production (<11 μl; comparable to Burger et al ()), and 6.4% had significantly reduced sweat duct counts and had overall reduced sweating volume compared to controls.…”

“…Ngoc et al () reported that all males ( n = 8) had slow growing, fragile and light‐colored hair but did not provide further details. Jones et al () reported that of 12 males, 100% had drastically slower growth of hairs compared to controls ( p = .0001), but the amount of hairs that were in growth phase were similar to controls. Yin et al () reported that of the 12 male Chinese subjects, 100% had hair that covered the vertex, although the hair was more fragile and thinner than controls.…”

“…Burger et al (2014) reported that the total mean hair count, follicle count, and individual hair width was reduced for 100% of 18 males. Jones et al (2013) also reported that the average hair count was reduced for 100% of 12 males. For both articles, the average total hair counts were <50% of the mean total hair counts for controls.…”

Estudio clínico y molecular en una familia con displasia ectodérmica hipohidrótica autosómica dominante

“…La gravedad de los signos y síntomas fue más leve que en las mutaciones encontradas en el gen EDA y, en particular, en las hipohidrosis. 7,14 Por lo general, el tratamiento es sintomático, con el uso de algunos productos farmacológicos por vía área, oral, en la piel y anexos según los requerimientos propios. El tratamiento antibioticoterápico puede emplearse de forma profiláctica o curativa.…”

Non‐invasive diagnosis of sweat gland dysplasia using optical coherence tomography and reflectance confocal microscopy in a family with anhidrotic ectodermal dysplasia (Christ–Siemens–Touraine syndrome)

“…The optical coherence tomography (OCT) and the reflectance confocal microscopy (RCM) are appropriate to measure sweat glands and sweat gland dysplasia and might be a helpful adjunctive tool in the early detection of genetic disorders as the anhidrotic ectodermal dysplasia. 17,18 The OCT offers cross-sectional images and a higher penetration depth and showed to be valuable in detecting the eccrine ducts. With the OCT the reduction of eccrine ducts in patients affected of an anhidrotic ectodermal dysplasia could be clearly seen.…”