Chapter 11 - Collagenopathies – The Ehlers-Danlos syndromes

Abstract

The Ehlers-Danlos syndromes (EDSs) are a group of rare heritable disorders of the connective tissue, characterised by generalised joint hypermobility, skin hyperextensibility and fragility, easy bruising, abnormal wound healing and widespread connective tissue fragility. Early ultrastructural and biochemical studies on skin samples from affected individuals revealed abnormalities of fibrillar collagens. With the introduction of sequencing techniques in the 1980s, molecular defects were indeed identified in genes coding for the fibrillar collagens, type I, III and V, or their modifying enzymes (lysyl hydroxylase 1 and the type I procollagen amino-proteinase ADAMTS2 (A Disintegrin And Metalloproteinase with Thrombospondin Motifs 2). Recent advances in molecular techniques also identified defects in other, non-collagenous extracellular matrix molecules, for example, the glycoprotein tenascin-X, enzymes involved in proteoglycan biosynthesis, the collagen chaperone FKBP22 and the complement factors C1r and C1s, significantly expanding the molecular and clinical spectrum of this syndrome. Despite this genetic heterogeneity, these defects all affect the supramolecular organisation of collagen fibrils at one level or another. As such, the EDSs are considered collagen-related disorders. Vascular complications, especially arterial dissections and ruptures, are most frequently observed in the vascular type of EDS, but cardiovascular complications can be seen in other EDS types as well. This chapter aims to provide the clinician an overview on the EDSs, their clinical presentation and molecular basis, and the cardio-vascular manifestations observed across the different types of EDS.