The third hallmark of the EEC syndrome is orofacial clefting, in particular lip and palate. p63 mutations also cause the other five inherited syndromes: symptoms are overlapping, but each of these diseases has its own characteristic phenotypic features: for instance AEC syndrome (ankyloblepharon-ectodermal defects-cleft lip/palate) has as distinctive feature ankyloblepharon, while mammary glands and nipples hypoplasia are frequent findings in LMS syndrome and in ADULT syndrome (acro-dermato-ungual-lacrimal-tooth syndrome).
EEC syndrome-specific mutations of TAp63γ fail to transactivate retSDR1 and an ADULT syndrome-derived mutant stimulates retSDR1 transcription significantly less than the wild-type variant of p63.
Mutant p63 proteins derived from EEC and ADULT syndrome patients cannot activate S100A2 transcription whereas SHFM-related mutants still can stimulate the S100A2 promoter.
ADULT syndrome has clinical overlap with other p63 mutation syndromes, such as EEC (OMIM 604292), LMS (OMIM 603543), AEC (106260), RHS (129400) and SHFM4 (605289).
This report expands the knowledge of genotype-phenotype data on the p63 gene and suggests there may be a considerable overlap between the EEC syndrome and the ADULT syndrome.
These results confirm that ADULT syndrome is a clinically as well as molecularly distinct member of the expanding p63 mutation family of human malformation syndromes.