Classical Ehlers-Danlos syndrome

Classical Ehlers-Danlos syndrome (cEDS), also known as EDS type I and type II or EDS gravis and mitis forms, is a heritable connective tissue disorder primarily caused by pathogenic variants in the COL5A1 or COL5A2 genes, which encode type V collagen. Rarely, specific variants in COL1A1 have also been identified. Type V collagen plays a critical role in regulating the assembly of collagen fibrils in skin, tendons, ligaments, blood vessels, and other organs, and its deficiency or structural abnormality leads to widespread connective tissue fragility. The hallmark clinical features of cEDS include marked skin hyperextensibility with a velvety texture, widened atrophic scarring (often described as "cigarette paper" or "papyraceous" scars), and generalized joint hypermobility. Patients frequently experience easy bruising, skin fragility, molluscoid pseudotumors, subcutaneous spheroids, and complications such as recurrent joint dislocations or subluxations. Hernias (inguinal, umbilical), pelvic organ prolapse, and mitral valve prolapse may also occur. Wound healing is significantly impaired, and surgical complications are common due to tissue fragility. Musculoskeletal pain, chronic fatigue, and functional disability are frequent concerns that affect quality of life. There is currently no cure or disease-modifying therapy for classical EDS. Management is supportive and multidisciplinary, focusing on skin protection, joint stabilization through physical therapy and bracing, pain management, and careful surgical planning with appropriate wound closure techniques. Patients benefit from genetic counseling, cardiovascular monitoring, and avoidance of contact sports or activities that place excessive strain on joints and skin. Ascorbic acid supplementation has been suggested but lacks strong evidence of efficacy. Early diagnosis and coordinated care can help reduce complications and improve long-term outcomes.

Common questions about Classical Ehlers-Danlos syndrome