Epidermolysis bullosa, pyloric atresia, aplasia cutis congenita: histopathological delineation of an autosomal recessive disease.
The simultaneous appearance of epidermolysis bullosa and pyloric atresia (EB-PA) is recognized as an autosomal recessive disease; however, the coappearance of EB-PA and aplasia cutis congenita (ACC) has not been delineated as a defined entity. The aim of this study was to analyze clinically and histopathologically eight cases with EB-PA-ACC belonging to an extended Bedouin family to gain insight into the cause and pathophysiology of the disease. All affected infants were found to have mixed skin lesions, including blisters and patchy lack of skin. Almost all of them (seven of eight) also had intestinal obstructions, especially pyloric atresia or stenosis. Skin lesions involved all skin layers with marked dystrophic changes. The intestinal obstruction was the result of overproliferation of connective tissue. In view of the clinical and histopathological findings, it is postulated that the condition is caused by an autosomal recessive gene affecting the integrity of the basement membrane and hemidesmosomes and the control of the normal process of fibrosis occurring during the course of wound healing. The sequence of events is initiated by the separation of the epidermis or the intestinal mucosal layer. Then, inflammatory reaction takes place and proceeds with massive fibrosis penetrating the deep layers and causing damage of skin and obstruction of the intestinal lumen. In view of the recent findings regarding the molecular basis of EB-PA, the described phenotype may result from a mutation in one of the integrin genes.
Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
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Maman
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Maor
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Kachko
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Carmi
D004476:Ectodermal Dysplasia / Q000150:complications / Q000235:genetics / Q000473:pathology*; D016108:Epidermolysis Bullosa Dystrophica / Q000150:complications / Q000235:genetics / Q000473:pathology*; D005260:Female; D005315:Fetal Diseases; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D010375:Pedigree; D011708:Pylorus / Q000002:abnormalities*