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A Skin Fragility Phenotype

Aimee S. Payne, MD, PhD; Albert C. Yan, MD; Erum Ilyas, MD; Weijie Li, MD, PhD; John T. Seykora, MD, PhD; Terri L. Young, MD; Bruce R. Pawel, MD; Paul J. Honig, MD; Jeanette Camacho, MD; Sonia Imaizumi, MD; Warren R. Heymann, MD; Rhonda E. Schnur, MD

Arch Dermatol. 2005;141:1567-1573.

Background  Ankyloblepharon, ectodermal defects, 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 suppressor TP53. Recent structure-function studies have identified complexities in the genotype-phenotype correlation of the p63 syndromes.

Observations  We report 2 sporadic cases of AEC syndrome in infants. Both patients demonstrated skin erosions with prominent scalp involvement. Histologic studies demonstrated mild basal layer vacuolization and rare dyskeratotic keratinocytes, with evidence of both acantholysis and cytolysis at the blister edge. Immunohistochemistry using anti-p63 monoclonal antibody demonstrated basal epidermal nuclear staining in both healthy control and patient tissue samples. Ultrastructural studies 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 analysis of each patient revealed 2 novel missense mutations in the TP63 gene that resulted in L514S and R555P amino acid substitutions within the sterile motif region of the p63 protein.

Conclusions  We report 2 novel TP63 mutations resulting in AEC syndrome. The R555P mutation is the most carboxy-terminal of all the reported AEC missense mutations of p63. The presence of skin fragility, manifested as erosive skin lesions in body areas in addition to the scalp, is postulated to be an important diagnostic feature of AEC syndrome.

Author Affiliations: Department of Dermatology (Drs Payne, Li, and Seykora), Division of Ophthalmology, Department of Surgery (Dr Young), and Division of Genetics, Department of Pediatrics (Dr Young), University of Pennsylvania, and Departments of Dermatology (Drs Yan and Honig) and Pathology (Dr Pawel), Children’s Hospital of Philadelphia, Philadelphia, Penn; and Division of Dermatology, Department of Medicine (Drs Ilyas and Heymann), Department of Pathology (Dr Camacho), and Divisions of Neonatology (Dr Imaizumi) and Genetics (Dr Schnur), Cooper University Hospital and Robert Wood Johnson Medical School, Camden, NJ. Dr Young is currently with the Departments of Ophthalmology and Pediatrics, Duke University Medical Center, Durham, NC.

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