Editorial: Research Advances in Understanding the Etiology, Epidemiology, Pathophysiology, Clinical Features and Management of the Ehlers-Danlos Syndrome Disorders Provisionally Accepted

Clair Francomano^1* Anne Maitland² Deborah Krakow³ Cheryl L. Maier⁴

• ¹School of Medicine, Indiana University Bloomington, United States
• ²Metrodora Institute, United States
• ³University of California, Los Angeles, United States
• ⁴School of Medicine, Emory University, United States

This collection of eight articles for Frontiers in Medicine, entitled Research Advances in Understanding the Etiology, Epidemiology, Pathophysiology, Clinical Features, and Management of the Ehlers-Danlos Syndrome Disorders, extends our knowledge base on EDS and HSD. The collection includes two qualitative studies, one on the array of associated pain syndromes and the second on the use of alternative and complementary medicine by persons living with hypermobile EDS. There are two review papers, focusing on the extracutaneous features and complications of EDS and another specifically on visual manifestations. A description of the neuroconnective endophenotype questionnaire and its validation discusses the interconnection of mind and body manifestations. The remaining articles, emerging from the allied health professions, include the following: balance and postural sway in patients with hypermobile EDS (hEDS); biochemical changes in the gastrocnemius medius-Achilles tendon complex in people with HSD; and the presentation and management of upper cervical instability in people with symptomatic generalized joint hypermobility. 2), pain was a common manifestation. Among the plethora of multisystem complications, ocular manifestations are noted, and these are expanded upon by the article in this collection by Asanad et al. (5). Doolan et al. also found that neuropsychiatric complications have been reported in almost all types of EDS, a finding that endorses the importance of the work by Bulbena et al. in this collection (6).The crucial interaction between body and mind should come as no surprise to any student of human nature. It is important to emphasize that these findings do not imply that the experience of complex symptoms for people living with EDS and HSD is "all in their head," as it has been pejoratively explained to many, but rather that the physiology of the body, impacted by the autonomic nervous system and the immune system, as well as the ubiquitous nature of the connective tissue, significantly perturb both physical and mental health.The allied health professions, including physical therapists, are assuming an increasing role in the optimal management of persons with EDS and HSD. Balance and proprioception are often impaired in these disorders. This may contribute to a fear of movement (kinesiophobia) and reduced activity, exacerbating the musculoskeletal complications emerging from hypermobility. The paper by Whitmore et al. in this collection (7) presents their findings on balance and sway in a population of persons with hEDS, and offers a range of diagnostic tools to help assess proprioception and balance as a means of measuring therapeutic progress.Alsiri and Palmer (8) utilized sonoelastography to assess the biomechanical impact of HSD on the elasticity of the gastrocnemius medius-Achilles tendon (GM-AT) complex. Their finding of increased elasticity at the GM-AT complex is further evidence of underlying connective tissue involvement in the HSD phenotype.Upper cervical instability, including instability at the craniocervical and/or atlo-axial junction, is likely under-recognized among persons with EDS and HSD. The work by Russek et al. (9) presents expert consensus recommendations for screening, assessing, and managing the complex symptoms associated upper cervical instability in the setting of symptomatic generalized joint hypermobility. This is an important contribution to the literature on the topic, providing a guide for the diagnosis and conservative management of these potentially devastating complications.Overall, EDS and HSD remain under-represented in the literature, but research efforts over the past decade have accelerated tremendously. The eight papers in this collection of Frontiers in Medicine represent hope for the future of people living with EDS, HSD and common co-morbidities, which so often dramatically impact quality of life. Much remains to be done.