Genotype–phenotype correlation in boys with X-linked hypohidrotic ectodermal dysplasia


  • Conflict of interest: Kenneth Huttner and Ramsey Johnson are employees of Edimer Pharmaceuticals, Inc., (Cambridge). K.H. contributed to the study design. R.J. performed the confocal microscopy. Holm Schneider is a member of the clinical advisory board of Edimer Pharmaceuticals and received funding from this company. Otherwise the sponsor was neither involved in collection, analysis, or interpretation of data, nor in the writing of the report or the decision to submit it for publication. The first draft of this manuscript was written by K.B. and H.S. None of the authors has been paid to produce this article.


X-linked hypohidrotic ectodermal dysplasia (XLHED), the most frequent form of ectodermal dysplasia, is a genetic disorder of ectoderm development characterized by malformation of multiple ectodermal structures such as skin, hair, sweat and sebaceous glands, and teeth. The disease is caused by a broad spectrum of mutations in the gene EDA. Although XLHED symptoms show inter-familial and intra-familial variability, genotype–phenotype correlation has been demonstrated with respect to sweat gland function. In this study, we investigated to which extent the EDA genotype correlates with the severity of XLHED-related skin and hair signs. Nineteen male children with XLHED (age range 3–14 years) and seven controls (aged 6–14 years) were examined by confocal microscopy of the skin, quantification of pilocarpine-induced sweating, semi-quantitative evaluation of full facial photographs with respect to XLHED-related skin issues, and phototrichogram analysis. All eight boys with known hypomorphic EDA mutations were able to produce at least some sweat and showed less severe cutaneous signs of XLHED than the anhidrotic XLHED patients (e.g., perioral and periorbital eczema or hyperpigmentation, regional hyperkeratosis, characteristic wrinkles under the eyes). As expected, individuals with XLHED had significantly less and thinner hair than healthy controls. However, there were also significant differences in hair number, diameter, and other hair characteristics between the group with hypomorphic EDA mutations and the anhidrotic patients. In summary, this study indicated a remarkable genotype–phenotype correlation of skin and hair findings in prepubescent males with XLHED. © 2014 Wiley Periodicals, Inc.