Multifaceted dermal ultrastructural clues for Ehlers-Danlos syndrome with arterial rupture and type I collagen R-to-C substitution.

Type I collagen arginine-to-cysteine (R-to-C) substitutions were found in three middle-aged adults suffering from spontaneous dissection of medium-size arteries. This disorder enters the heterogeneous spectrum of the Ehlers-Danlos syndrome (EDS). Despite similar genetic mutation and arterial alterations, two distinct clinical presentations were identified showing signs of either the EDS classic type or premature osteopenia alone. Ultrastructural changes were found in the dermal collagen fibrils, elastic fibers, and proteoglycan components. The cross-section of most collagen fibrils was rounded, but with diverse diameters. Flower-like outlines of collagen fibrils were rarely disclosed. Large hyaluronic acid globules pushed apart the collagen bundles in the case with EDS classic-type presentation. Elastic fibers contained unusual annular microcalcifications. In conclusion, ultrastructural changes were found in diverse connective-tissue components despite the fact that the mutations were found to be specific for the collagen molecules. In addition, two distinct clinical presentations were found and were correlated with peculiar ultrastructural alterations.