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Pathologic changes of skin and hair in ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome

Department of Pathology, Texas Children's Hospital, Baylor College of Medicine, 6621 Fannin, Houston, TX 77030, USA.
American Journal of Medical Genetics Part A (Impact Factor: 2.05). 09/2009; 149A(9):1935-41. DOI: 10.1002/ajmg.a.32826
Source: PubMed

ABSTRACT Ankyloblepharon-Ectodermal defects-Cleft lip/palate (AEC) syndrome is a rare disorder of hair, skin, nails, and dentition caused by mutations in the p63 gene. Pathologic changes of skin and hair in AEC syndrome have previously been described in isolated case reports. Biopsies of normal and lesional skin from 19 patients with AEC syndrome were examined by light microscopy. Hair samples from 18 patients were examined by light and scanning electron microscopy. Histopathologic changes identified within the skin biopsies from clinically unaffected skin include mild atrophy, focal orthokeratosis, and mild superficial perivascular lymphocytic dermatitis. Scattered melanophages in the superficial and deep dermis likely reflect post-inflammatory change. One patient with a unilateral eruption of monomorphic papulopustules on the chest and shoulder demonstrated an acneiform intraepidermal pustule. Examination of the hair shafts revealed atrophy and loss of melanin pigment in some of the patients. Structural abnormalities included pili torti, pili trianguli et canaliculi, and irregular indentation and shallow grooves. Skin and hair findings in AEC syndrome were found to be generally similar to those described in other ectodermal dysplasia syndromes and corroborates the few prior descriptions in AEC syndrome specifically.

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    • "Cleft palate was not rescued by crossing chimeras with females of different inbred strains ( see Supporting information ) suggesting that this defect was independent of the genetic background . Ankyloblepharon - ectodermal defects - cleft lip / palate patients are characterized by mild atrophy of the skin , skin erosions and sparse or absent hair ( Dishop et al , 2009 ; McGrath et al , 2001 ) . p63 þ / L514F mice displayed reduced skin folding and a translucent appearance of the skin at birth ( Supporting Information Fig S3A ) . "
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    ABSTRACT: Dominant mutations in TP63 cause ankyloblepharon ectodermal dysplasia and clefting (AEC), an ectodermal dysplasia characterized by skin fragility. Since DeltaNp63alpha is the predominantly expressed TP63 isoform in postnatal skin, we hypothesized that mutant DeltaNp63alpha proteins are primarily responsible for skin fragility in AEC patients. We found that mutant DeltaNp63alpha proteins expressed in AEC patients function as dominant-negative molecules, suggesting that the human AEC skin phenotype could be mimicked in mouse skin by downregulating DeltaNp63alpha. Indeed, downregulating DeltaNp63 expression in mouse epidermis caused severe skin erosions, which resembled lesions that develop in AEC patients. In both cases, lesions were characterized by suprabasal epidermal proliferation, delayed terminal differentiation, and basement membrane abnormalities. By failing to provide structural stability to the epidermis, these defects likely contribute to the observed skin fragility. The development of a mouse model for AEC will allow us to further unravel the genetic pathways that are normally regulated by DeltaNp63 and that may be perturbed in AEC patients. Ultimately, these studies will not only contribute to our understanding of the molecular mechanisms that cause skin fragility in AEC patients, but may also result in the identification of targets for novel therapeutic approaches aimed at treating skin erosions. (c) 2009 Wiley-Liss, Inc.
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