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.
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.
KeywordsEctodermal dysplasia Sweat glands p63 AEC syndrome EEC syndrome Hypohidrosis
Ankyloblepharon-ectodermal dysplasia-cleft lip/palate
Ectrodactyly-ectodermal dysplasia-cleft lip/palate
Sterile alpha motif
We would like to express our gratitude to all individuals who participated in the study.
P.F. and H.S. conceived the study, investigated the patients, and wrote the first draft of the manuscript. Most of the work was performed by P.F. in fulfillment of the requirements for obtaining the degree “Dr. med.” from the Friedrich-Alexander-Universität Erlangen-Nürnberg. S.W. provided essential assistance with the confocal laser scanning microscopy. All authors reviewed the results and approved the final version of the manuscript.
This study was funded by the German-Swiss-Austrian ectodermal dysplasia patient organization.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All adult participants provided written informed consent; in the case of minors, parental consent was obtained.
- 3.Celli J, Duijf P, Hamel BC, Bamshad M, Kramer B, Smits AP, Newbury-Ecob R, Hennekam RC, van Buggenhout G, van Haeringen A, Woods CG, van Essen AJ, de Waal R, Vriend G, Haber DA, Yang A, McKeon F, Brunner HG, van Bokhoven H (1999) Heterozygous germ line mutations in the p53 homolog p63 are the cause of EEC syndrome. Cell 99:143–153CrossRefGoogle Scholar
- 8.Russo C, Osterburg C, Sirico A, Antonini D, Ambrosio R, Würz JM, Rinnenthal J, Ferniani M, Kehrloesser S, Schäfer B, Güntert P, Sinha S, Dötsch V, Missero C (2018) Protein aggregation of the p63 transcription factor underlies severe skin fragility in AEC syndrome. Proc Natl Acad Sci U S A 115:E906–E915CrossRefGoogle Scholar
- 10.Schneider H, Faschingbauer F, Schuepbach-Mallepell S, Körber I, Wohlfart S, Dick A, Wahlbuhl M, Kowalczyk-Quintas C, Vigolo M, Kirby N, Tannert C, Rompel O, Rascher W, Beckmann MW, Schneider P (2018) Prenatal correction of X-linked hypohidrotic ectodermal dysplasia. New Engl J Med 378:1604–1610CrossRefGoogle Scholar