Abstract
Hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) are increasingly recognized as complex, multisystem connective tissue disorders characterized by joint hypermobility and instability, chronic pain, autonomic dysfunction, immune dysregulation, and structural fragility. Despite their clinical impact and prevalence, the underlying pathophysiology remains poorly understood, and diagnosis is frequently delayed or missed altogether. Emerging research highlights the fascia as a central player in the pathogenesis of these conditions. This narrative review synthesizes current molecular, histological, and biomechanical findings to propose a fascia-centered framework for understanding hEDS and HSD. Evidence from transcriptomic and imaging studies reveals consistent abnormalities in fascial thickness, interfascial gliding, myofibroblast activation, tendon elongation, and tissue stiffness-findings that mirror the functional impairments reported in clinical populations. We explore fascia as a dynamic tissue network and consider how dysregulation in these processes may contribute to the widespread symptoms seen in hypermobility disorders. By reframing hEDS and HSD as disorders of pathological fascial remodeling, this review offers an integrated model that connects molecular mechanisms with clinical expression. It underscores the urgent need for multidisciplinary research to define diagnostic biomarkers, clarify therapeutic targets, and support the development of more effective, personalized interventions.