The Expanding Multisystem Research Landscape of Hypermobile Ehlers-Danlos Syndrome: An Analysis of Orthopedic, Autonomic, Immunologic, and Neuropsychiatric Comorbidities

Introduction

Hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorder (HSD) are increasingly recognized among orthopedic physicians to cause joint instability, frequent dislocation, and chronic musculoskeletal pain. Yet, patients with these disorders frequently have coexisting conditions, such as postural tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), autoimmune and allergic disease, and neuropsychiatric conditions including anxiety, depression, ADHD, and autism. These comorbidities complicate diagnosis and treatment, therefore potentially decreasing the overall quality of care these patients receive. Despite the clinical relevance of comorbidities, the extent of research linking hypermobility disorders to these conditions has not been comprehensively examined.