UNASSIGNED: Ehlers-Danlos syndrome (EDS) and hypermobility spectrum disorders (HSD) are associated with impairments in balance and physical function. However, the psychometric properties of relevant outcome measures remain largely unexplored. The objectives of this study were to evaluate the construct validity of the Mini-Balance Evaluation Systems Test (Mini-BESTest) alongside the test-retest reliability of the Mini-BESTest, Six Minute Walk Test (6MWT), and Lower Extremity Functional Scale (LEFS) in patients with the hypermobility subtype of EDS (hEDS) and HSD.
UNASSIGNED: Participants with hEDS/HSD (n = 20) attended two visits scheduled one to two weeks apart. The construct validity of the Mini-BESTest was determined through Pearson correlations between force plate balance measures, 6MWT, and LEFS. Test-retest reliability of the measures was evaluated through intraclass correlation coefficients (ICC). Minimal detectable change values with 95% confidence (MDC95) were also calculated.
UNASSIGNED: Mini-BESTest demonstrated significant correlations with force plate measures, 6MWT, and LEFS (r = -0.41 to 0.66). Test-retest reliability was excellent for the Mini-BESTest, 6MWT, and LEFS (ICC = 0.91 to 0.96). MDC95 was 4 for the Mini-BESTest, 77 m for the 6MWT, and 11 for the LEFS.
UNASSIGNED: The Mini-BESTest is valid and reliable for assessing balance and mobility in patients with hEDS/HSD.IMPLICATIONS FOR REHABILITATIONThe Mini Balance Evaluation Systems Test (Mini-BESTest) is valid in capturing aspects of balance and physical function in patients with hypermobile Ehlers-Danlos syndrome or hypermobility spectrum disorders.However, the Mini-BESTest may show a potential ceiling effect for high functioning patients in this population.The Mini-BESTest, 6 Minute Walk Test, and the Lower Extremity Functional Scale also show excellent test-retest reliability in this population.The Minimal Detectable Change with 95% confidence intervals is 4 for the Mini-BESTest, 77 m for the 6 Minute Walk Test, and 11 for the Lower Extremity Functional Scale in this population.

BACKGROUND: Joint hypermobility (JH) represents the extreme of the normal range of motion or a condition for a group of genetically determined connective tissue disorders. Generalized joint hypermobility (GJH) is suspected when present in all four limbs and the axial skeleton, scored in prepubescent children and adolescents by a Beighton Score (BS) ≥ 6. Parameters are also used to identify GJH in hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSDs). The purpose of this study is to characterize children with JH based on the location of variables in the BS ≥ 6 and identify children with JH in the axial skeleton, upper limbs (ULs), and lower limbs (LLs) simultaneously.
METHODS: We analyzed 124 medical records of one- to nine-year-old children with JH by BS.
RESULTS: The characterization of GJH by combinations of the axial skeleton, ULs, and LLs simultaneously totaled 25.7%. BS = 6 and BS = 8 consisted of variables located in ULs and LLs. BS = 7 included the axial skeleton, ULs, and LLs. BS ≥ 6 represents the majority of the sample and predominantly girls.
CONCLUSIONS: BS ≥ 6 represents the majority of the sample and predominantly girls. Most characterized children with GJH present BS = 6 and BS = 8 with variables located only in ULs and LLs, a condition that does not imply the feature is generalized. In children, BS = 7 and BS = 9 characterize GJH by including the axial skeleton, ULs, and LLs. These results draw attention to the implications for defining the diagnosis of hEDS and HSDs.

The most common conditions with symptomatic joint hypermobility are hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD). Diagnosing these overlapping connective tissue disorders remains challenging due to the lack of established causes and reliable diagnostic tests. hEDS is diagnosed applying the 2017 diagnostic criteria, and patients with symptomatic joint hypermobility but not fulfilling these criteria are labeled as HSD, which is not officially recognized by all healthcare systems. The 2017 criteria were introduced to improve diagnostic specificity but have faced criticism for being too stringent and failing to adequately capture the multisystemic involvement of hEDS. Herein, we retrospectively evaluated 327 patients from 213 families with a prior diagnosis of hypermobility type EDS or joint hypermobility syndrome based on Villefranche and Brighton criteria, to assess the effectiveness of the 2017 criteria in distinguishing between hEDS and HSD and document the frequencies of extra-articular manifestations. Based on our findings, we propose that the 2017 criteria should be made less stringent to include a greater number of patients who are currently encompassed within the HSD category. This will lead to improved diagnostic accuracy and enhanced patient care by properly capturing the diverse range of symptoms and manifestations present within the hEDS/HSD spectrum.

Two thirds of the patients we believed to have IBS in the 1970\'s have since been possible to diagnose with treatable conditions like bile acid diarrhea, inflammatory bowel disease, microscopic colitis, celiac disease, disaccharide malabsorption, exocrine pancreatic insufficiency, or rare genetic variants. Despite advances in diagnostic techniques a substantial proportion of patients continue suffering from IBS-like symptoms that cannot be explained by current knowledge. Although it is likely that further research will reveal small but important subgroups of patients with treatable mechanisms for IBS-like symptoms, we propose that only two large groups remain for being addressed in the clinic: those with connective tissue disorders such as Ehlers-Danlos syndrome or hypermobility spectrum disorders and those with autism spectrum disorders. Patients with connective tissue disorders exhibit identifiable disturbances of gut motor function and possibly increased gut permeability as underlying mechanisms for IBS-like symptoms. Autism spectrum disorders pose a much more difficult problem in the clinic. Disturbances of perception combined with anxiety and excessive worry about signals from the gut can lead to an endless but futile search for something being wrong. The search can involve large numbers of care givers, no one understanding the patient\'s suffering. Others may try to change their diet to lessen symptoms, only to find that almost all foods may cause worrying perceptions from the gut. Early recognition of autism spectrum disorders is essential for finding better ways to help patients with gastrointestinal and, as is often the case, extraintestinal symptoms.

Joint hypermobility (JHM) is a common physical trait. It may occur alone or in combination with musculoskeletal (MSK) pain, outside or within more complex phenotypes. Hypermobility spectrum disorders (HSD) are diagnosed in individuals with JHM and related MSK pain, when an alternative diagnosis cannot be identified. Conversely, the Ehlers-Danlos syndrome (EDS) encompasses a group of rare hereditary connective tissue disorders featuring JHM along with other pleiotropic manifestations. The 2017 EDS Classification identifies 13 different subtypes. Hypermobile EDS (HEDS) is the only EDS variant still lacking a confirmatory test.
Literature was reviewed searching for the most relevant papers related to key arguments. Particular attention was focused on papers published after the 2017 Classification.
Definition, epidemiology, assessment tools and patterns of JHM are presented. The morbid nature of the 2017 EDS Classification and of the \'spectrum\' is also illustrated.
We discuss current limitations and disagreements concerning the \'spectrum\', HSD and HEDS.
In the clinical context, elucidation of the pathophysiology of pain related to JHM should develop in parallel with the analysis of pleiotropic manifestations of syndromes with JHM.
Future challenges concerning classification, nosology, diagnosis and management of JHM, EDS and related disorders are discussed.

OBJECTIVE: To assess the association between hypermobility spectrum disorders/hypermobile type Ehlers Danlos Syndrome (HSD/hEDS) and migraine in a national sample of adolescents in Israel.
BACKGROUND: The association between HSD/hEDS and migraine is unclear, even more so in pediatric populations.
METHODS: This population-based, cross-sectional study included 1,627,345 Israeli adolescents (945,519/1,626,407 [58%] males; mean age 17 ± 0.5 years) who were medically assessed before mandatory military service during 1998-2020. Diagnoses of migraine with at least one attack per month (active migraine) and HSD/hEDS were confirmed by certified specialists. The prevalences of active migraine in adolescents with and without HSD/hEDS were computed and the association between HSD/hEDS and active migraine was examined.
RESULTS: Active migraine was significantly more prevalent in adolescents with HSD/hEDS (307/4686 [6.5%]) compared to those without HSD/hEDS (51,931/1,621,721 [3.2%]) (OR = 2.16, 95% CI 1.90-2.45). The association between HSD/hEDS and active migraine persisted in a multivariable analysis (OR = 2.08, 95% CI 1.85-2.34) and in several sensitivity analyses.
CONCLUSIONS: We found a significant association between HSD/hEDS and active migraine in both male and female adolescents. Clinical awareness of the association can promote early diagnosis and treatment of migraine. Further research is required to identify appropriate pharmacologic and nonpharmacologic migraine treatment strategies for individuals with HSD/hEDS.

UNASSIGNED: Joint pain is a common symptom in patients with hypermobile Ehlers-Danlos Syndrome (hEDS), hypermobility spectrum disorders (HSD) and fibromyalgia. The goal of this study was to determine whether symptoms and comorbidities overlap in patients diagnosed with hEDS/HSD and/or fibromyalgia.
UNASSIGNED: We retrospectively examined self-reported data from an EDS Clinic intake questionnaire in patients diagnosed with hEDS/HSD, fibromyalgia, or both vs. controls with an emphasis on joint issues.
UNASSIGNED: From 733 patients seen at the EDS Clinic, 56.5% (n = 414) were diagnosed with hEDS/HSD and fibromyalgia (Fibro), 23.8% (n = 167) hEDS/HSD, 13.3% (n = 98) fibromyalgia, or 7.4% (n = 54) none of these diagnoses. More patients were diagnosed with HSD (76.6%) than hEDS (23.4%). Patients were primarily White (95%) and female (90%) with a median age in their 30s (controls 36.7 [18.0, 70.0], fibromyalgia 39.7 [18.0, 75.0], hEDS/HSD 35.0 [18.0, 71.0], hEDS/HSD&Fibro 31.0 [18.0, 63.0]). There was high overlap in all 40 symptoms/comorbidities that we examined in patients diagnosed with fibromyalgia only or hEDS/HSD&Fibro, regardless of whether they had hEDS or HSD. Patients that only had hEDS/HSD without fibromyalgia had far fewer symptoms/comorbidities than patients with hEDS/HSD&Fibro. The top self-reported issues in patients that only had fibromyalgia were joint pain, hand pain when writing or typing, brain fog, joint pain keeping from daily activities, allergy/atopy and headache. Five issues that significantly and uniquely characterized patients diagnosed with hEDS/HSD&Fibro were subluxations (dislocations in hEDS patients), joint issues like sprains, the need to stop sports due to injuries, poor wound healing, and migraine.
UNASSIGNED: The majority of patients seen at the EDS Clinic had a diagnosis of hEDS/HSD plus fibromyalgia that was associated with more severe disease. Our findings indicate that fibromyalgia should be routinely assessed in patients with hEDS/HSD and vis-a-versa to improve patient care.

BACKGROUND: Technological improvements alone have not led to the integration of genomic medicine across a broad range of diseases and populations. For genomic medicine to be successfully implemented across specialties and conditions, the challenges patients and caregivers experience need to be identified using a multi-faceted understanding of the context in which these obstacles occur and how they are experienced. Individuals affected by rare conditions, like Ehlers-Danlos syndromes (EDS) and hypermobility spectrum disorders (HSD), express numerous challenges with accessing genomic medicine. Many patients living with rare diseases seek information and find comfort in online health communities.
METHODS: Social media conversations facilitated through online health communities are windows into patients\' and caregivers\' authentic experiences. To date, no other study has examined genomic medicine barriers by analysing the content of social media posts, yet the novel methodological approach of social media listening permits the analysis of virtual, organic conversations about lived experiences.
CONCLUSIONS: Using a modified social-ecological model, this study found that social-structural and interpersonal barriers most frequently impede access to genomic medicine for patients and caregivers living with EDS and HSD.
UNASSIGNED: Data were retrieved through social media conversations facilitated through publicly accessible health communities through Inspire, an online health community. Social media listening permits the analysis of virtual, organic conversations about lived experiences.

Hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorders cause joint instability, chronic pain, fatigue and progressive multisystemic dysfunction, increasing symptom burden and decreasing quality of life. Researchers know little about how these disorders progress in women as they age.
This research aimed to determine the feasibility of an internet-based study to understand the clinical characteristics, symptom burden and health-related quality of life in older women with symptomatic hypermobility disorders.
This cross-sectional, internet-based survey studied recruitment methods, suitability and usability of survey instruments and obtained baseline data on women aged 50 and older with hEDS/HSD. Researchers recruited participants from a Facebook group for older adults with Ehlers-Danlos syndrome. Outcome measures included health history, the Multidimensional Health Assessment Questionnaire and the RAND Short Form 36 health survey.
Researchers recruited 32 participants from a single Facebook group within 2 weeks. Nearly all participants were satisfied with the survey length, clarity and navigation, with 10 participants providing free-text recommendations for survey improvement. The survey suggests a high symptom burden and poor quality of life in older women with hEDS/HSD.
The results support the feasibility and importance of a future internet-based comprehensive study about hEDS/HSD in older women.

Hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) are clinically overlapping connective tissue disorders of unknown etiology and without any validated diagnostic biomarker and specific therapies. Herein, we in-depth characterized the cellular phenotype and gene expression profile of hEDS and HSD dermal fibroblasts by immunofluorescence, amplicon-based RNA-seq, and qPCR. We demonstrated that both cell types show a common cellular trait, i.e., generalized extracellular matrix (ECM) disarray, myofibroblast differentiation, and dysregulated gene expression. Functional enrichment and pathway analyses clustered gene expression changes in different biological networks that are likely relevant for the disease pathophysiology. Specifically, the complex gene expression dysregulation (mainly involving growth factors, structural ECM components, ECM-modifying enzymes, cytoskeletal proteins, and different signal transducers), is expected to perturb many ECM-related processes including cell adhesion, migration, proliferation, and differentiation. Based on these findings, we propose a disease model in which an unbalanced ECM remodeling triggers a vicious cycle with a synergistic contribution of ECM degradation products and proinflammatory mediators leading to a functional impairment of different connective tissues reflecting the multisystemic presentation of hEDS/HSD patients. Our results offer many promising clues for translational research aimed to define molecular bases, diagnostic biomarkers, and specific therapies for these challenging connective tissue disorders.