Genotype-phenotype correlation in boys with X-linked hypohidrotic ectodermal dysplasia.
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.
Department of Pediatrics, German Competence Center for Children with Ectodermal Dysplasias, University Hospital Erlangen, University of Erlangen-Nürnberg, Germany.
Kristin
K
Burger
Anne-Theres
AT
Schneider
Sigrun
S
Wohlfart
Franklin
F
Kiesewetter
Kenneth
K
Huttner
Ramsey
R
Johnson
Holm
H
Schneider
D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004476:Ectodermal Dysplasia / Q000235:genetics*; D056726:Genetic Association Studies / Q000379:methods; D005838:Genotype; D006197:Hair / Q000473:pathology; D006801:Humans; D007007:Hypohidrosis / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics; D012867:Skin / Q000473:pathology; D013545:Sweat Glands / Q000473:pathology; D013546:Sweating / Q000235:genetics
EDA; ectodysplasin; genotype-phenotype correlation; hair; hypohidrotic ectodermal dysplasia; sweat glands