Biochemical, morphological and stereological study of the dermis in three members of a large family with type IV Ehlers-Danlos syndrome.

Biochemical, morphological and stereological studies were carried out on dermal biopsies obtained from three members of a large family with a positive clinical history of type IV Ehlers-Danlos syndrome. Ultrastructural analysis showed that fibroblasts from two affected individuals presented abnormally dilated rough endoplasmic reticulum cisternae engorged by microfilamentous material. When cultured, fibroblasts from two affected individuals synthesized and secreted normal amounts of type I procollagen, but only a very low percentage of type III procollagen was secreted. Cellular retention of type III procollagen was confirmed by immunofluorescence. Also the secretion of fibronectin appeared delayed. Stereological analysis carried out on semithin sections of dermis by the point counting method showed that the relative volume of collagen fibers was decreased in the reticular dermis and the relative volume of elastin fibers was increased mainly in the upper layer of reticular dermis, in comparison to normal controls (P less than 0.01). Collagen fiber sizes were significantly (P less than 0.01) reduced in all dermis layers. No alterations were seen in the dermis and in cultured fibroblasts from the clinically normal individual.