Abnormal collagen fibril structure in the gravis form (type I) of Ehlers-Danlos syndrome

Abstract

The Ehlers-Danlos syndrome (EDS) is a clinically, genetically, and biochemically heterogeneous group of disorders characterized by generalized connective tissue abnormalities. We studied collagen fibrils by electron microscopy in the dermis of nine individuals with clinical findings consistent with type I Ehlers-Danlos syndrome. In all patients the collagen fibrils had an increased mean diameter (13 to 40%) and showed a higher degree of variability in width and shape than collagen fibrils from controls. Approximately 5% of the fibrils were much wider (up to 500 nm. versus 90 nm.), had a highly irregular outline when viewed in cross-section, and were spiraled and fragmented in longitudinal view. The periodicity of banding was normal. The mode of inheritance was dominant in five patients, probably recessive in two, and could not be determined in the remaining two. Despite genetic heterogeneity among these patients with type I Ehlers-Danlos syndrome, the ultrastructural findings are indistinguishable and do not allow discrimination in sporadic cases between the recessive and the more common dominant form. We conclude that abnormalities of fibrillogenesis are heterogeneous in origin; some might be due to primary defects in collagen whereas others may result from alterations of noncollagenous extracellular matrix components that influence collagen fibril formation.