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.
- Ectodermal dysplasia
- sweat gland
- clinical genetics
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Funding This study was supported partially by the German-Swiss-Austrian ectodermal dysplasia patient support group and by a grant from Edimer Pharmaceuticals (Cambridge, USA).
Competing interests One of the authors (KH) is an employee of Edimer Pharmaceuticals. He contributed to study design and interpretation of the final results. 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 HS and AB. None of the authors has been paid to produce this article.
Ethics approval This study was conducted with the approval of the Ethics Committee of the University of Erlangen-Nürnberg.
Provenance and peer review Not commissioned; externally peer reviewed.