Two Novel TP63 Mutations Associated With the Ankyloblepharon, Ectodermal Defects, and Cleft Lip and Palate Syndrome

Background:Ankyloblepharon,ectodermaldefects,and cleft lip and palate (AEC) syndrome is a rare autosomal dominant disorder caused by mutations in the sterile motif region of TP63, a homologue of the tumor sup- pressorTP53.Recentstructure-functionstudieshaveiden- tified complexities in the genotype-phenotype correla- tion of the p63 syndromes. Observations:We report 2 sporadic cases of AEC syn- drome in infants. Both patients demonstrated skin ero- sionswithprominentscalpinvolvement.Histologicstud- ies demonstrated mild basal layer vacuolization and rare dyskeratotic keratinocytes, with evidence of both acan- tholysis and cytolysis at the blister edge. Immunohisto- chemistry using anti-p63 monoclonal antibody demon- strated basal epidermal nuclear staining in both healthy control and patient tissue samples. Ultrastructural stud- ies showed focal disruption of anchoring fibrils near the blister edge of one patient and normal desmosomes, hemidesmosomes, and basement membrane zone in the nonblistered skin of the other patient. The DNA analy- sis of each patient revealed 2 novel missense mutations intheTP63genethatresultedinL514SandR555Pamino acid substitutions within the sterilemotif region of the p63 protein. Conclusions:We report 2 novelTP63mutations result- ing in AEC syndrome. The R555P mutation is the most carboxy-terminal of all the reported AEC missense mu- tations of p63. The presence of skin fragility, mani- fested as erosive skin lesions in body areas in addition to the scalp, is postulated to be an important diagnostic feature of AEC syndrome. Arch Dermatol. 2005;141:1567-1573