Clinical meaning
Ehlers-Danlos syndromes (EDS) are a heterogeneous group of heritable connective tissue disorders caused by genetic defects in collagen synthesis, structure, or processing. Collagen is the most abundant protein in the human body, providing structural integrity to skin, blood vessels, joints, organs, and virtually all connective tissues. Normal collagen biosynthesis involves transcription of procollagen alpha chains, hydroxylation of proline and lysine residues (requiring vitamin C as cofactor), triple helix formation, secretion, extracellular cleavage of propeptides, and cross-linking into mature collagen fibrils. EDS subtypes result from mutations affecting different steps in this pathway or different collagen types. The most common subtype, hypermobile EDS (hEDS), has no identified causative gene and is diagnosed clinically; the genetic basis likely involves multiple genes affecting extracellular matrix organization. Classical EDS (cEDS) results from mutations in COL5A1 or COL5A2 (type V collagen), causing defective collagen fibril assembly with characteristic skin hyperextensibility, atrophic scarring, and joint hypermobility. Vascular EDS (vEDS) -- the most dangerous subtype -- is caused by mutations in COL3A1 (type III collagen), which is the predominant collagen of blood vessel walls, hollow organs, and the uterus; deficient type III collagen leads to fragile arterial walls prone to spontaneous dissection and rupture, and hollow organ perforation. The Beighton score (0-9 points) quantifies generalized joint hypermobility by testing bilateral passive dorsiflexion of the 5th metacarpophalangeal joint beyond 90°, bilateral passive apposition of the thumb to the forearm, bilateral hyperextension of the elbow beyond 10°, bilateral hyperextension of the knee beyond 10°, and ability to place palms flat on the floor with knees locked. A score of ≥5/9 (≥4/9 for adults >50 years) indicates generalized joint hypermobility. The 2017 International Classification recognizes 13 EDS subtypes, each with specific clinical criteria and genetic testing recommendations.