EPIDERMOLYSIS-BULLOSA, PYLORIC ATRESIA, APLASIA-CUTIS-CONGENITA - HISTOPATHOLOGICAL DELINEATION OF AN AUTOSOMAL RECESSIVE DISEASE

The simultaneous appearance of epidermolysis bullosa and pyloric atres ia (EB-PA) is recognized as an autosomal recessive disease; however, t he coappearance of EB-PA and aplasia cutis congenita (ACC) has not bee n delineated as a defined entity. The aim of this study was to analyze clinically and histopathologically eight cases with EB-PA-ACC belongi ng to an extended Bedouin family to gain insight into the cause and pa thophysiology 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, especi ally pyloric atresia or stenosis, Skin lesions involved all skin layer s with marked dystrophic changes, The intestinal obstruction was the r esult of overproliferation of connective tissue, In view of the clinic al and histopathological findings, it is postulated that the condition is caused by an autosomal recessive gene affecting the integrity of t he 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 cau sing damage of skin and obstruction of the intestinal lumen. In view o f the recent findings regarding the molecular basis of EB-PA, the desc ribed phenotype may result from a mutation in one of the integrin gene s. Am. J, Med, Genet, 78:127-133, 1998, (C) 1998 Wiley-Liss, Inc.