Sweating ability of patients with p63-associated syndromes

Eur J Pediatr. 2018 Nov;177(11):1727-1731. doi: 10.1007/s00431-018-3227-6. Epub 2018 Aug 7.


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.Conclusion: Hypohidrosis in p63-associated syndromes is less common and potentially less severe than previously thought and may be attributable to certain genotypes. 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.

Keywords: AEC syndrome; EEC syndrome; Ectodermal dysplasia; Hypohidrosis; Sweat glands; p63.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Cleft Lip / complications*
  • Cleft Lip / genetics
  • Cleft Palate / complications*
  • Cleft Palate / genetics
  • Ectodermal Dysplasia / complications*
  • Ectodermal Dysplasia / genetics
  • Eye Abnormalities / complications*
  • Eye Abnormalities / genetics
  • Eyelids / abnormalities*
  • Female
  • Genetic Association Studies
  • Humans
  • Hypohidrosis / etiology*
  • Male
  • Middle Aged
  • Mutation
  • Pilocarpine / administration & dosage
  • Sweat Glands / abnormalities
  • Sweating / physiology
  • Transcription Factors / genetics*
  • Tumor Suppressor Proteins / genetics*
  • Young Adult


  • TP63 protein, human
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Pilocarpine

Supplementary concepts

  • Ectrodactyly-cleft lip-palate syndrome
  • Hay-Wells syndrome