Materiały źródłowe

• #1 Joint Hypermobility Syndrome and Membrane Proteins: A Comprehensive Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11048254/

  Joint hypermobility syndrome (JHS) is a connective tissue disorder characterized by extreme flexibility of the joints, along with pain and other symptoms. […] The exact cause of JHS could be related to genetic changes in the proteins that add flexibility and strength to the joints, ligaments, and tendons, such as collagen. […] Recent studies have suggested that membrane proteins may also play a role in the pathogenesis of JHS. […] The integrin profile observed in EDS/HSD reveals a downregulation of the collagen receptor, 21 integrin, and the fibronectin receptor, 51 integrin, accompanied by an upregulation of the vitronectin receptor, v3 integrin. […] This distinctive integrin expression pattern is coined the integrin switch, a phenomenon replicated in control cells through functional blocking of the 21 receptor.

• #2 Joint Hypermobility Syndrome and Membrane Proteins: A Comprehensive Review – PubMed

  https://pubmed.ncbi.nlm.nih.gov/38672488/

  Ehlers-Danlos syndromes (EDSs) constitute a heterogeneous group of connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. […] Joint hypermobility syndrome (JHS) is a connective tissue disorder characterized by extreme flexibility of the joints, along with pain and other symptoms. […] The exact cause of JHS could be related to genetic changes in the proteins that add flexibility and strength to the joints, ligaments, and tendons, such as collagen. […] recent studies have suggested that membrane proteins may also play a role in the pathogenesis of JHS. […] It aims to provide an understanding of JHS and its association with membrane proteins, addressing the clinical manifestations, pathogenesis, diagnosis, and management of JHS.

• #3 Joint Hypermobility Syndrome: Symptoms, Causes, Diagnosis & Treatments

  https://my.clevelandclinic.org/health/diseases/21763-joint-hypermobility-syndrome

  Joint hypermobility syndrome is a connective tissue disorder. Thick bands of tissue (ligaments) hold your joints together and keep them from moving too much or too far out of range. In people with joint hypermobility syndrome, those ligaments are loose or weak. If you have joints that are more flexible than normal and it causes you pain, you may have joint hypermobility syndrome. […] The exact cause of joint hypermobility syndrome isnt known. However, the disorder tends to run in families. The genes that are involved in the creation of collagen are believed to play a role. Collagen is the protein that adds flexibility and strength to your joints, ligaments and tendons. People with joint hypermobility syndrome have loose joints because they have weak ligaments. They have weak ligaments because of the defect in their collagen.

• #4 Joint hypermobility syndrome

  https://www.nhs.uk/conditions/joint-hypermobility-syndrome/

  Joint hypermobility syndrome can run in families and it cannot be prevented. […] Usually, the joints are loose and stretchy because the ligaments that should make them stronger and support them are weak. […] The weakness is because the collagen that strengthens the ligaments is different from other people’s. […] Most experts agree that joint hypermobility syndrome is part of a spectrum of hypermobility disorders which includes Ehlers-Danlos syndrome.

• #5 Joint Hypermobility Syndrome and Membrane Proteins: A Comprehensive Review

  https://www.mdpi.com/2218-273X/14/4/472

  The collagen family comprises 28 members, expressed by 43 genes, and characterized by the shared triple helix motif. […] Mutations occurring in collagen genes, notably types III and V, are significant contributors to the development of Ehlers–Danlos syndrome (EDS). […] In joint hypermobility syndrome/Ehlers–Danlos syndrome hypermobility type (JHS/EDS-HT), mutations in type III collagen can lead to either EDS IV or EDS II. […] The diagnosis of the kyphoscoliotic type of Ehlers–Danlos syndrome (kEDS) represents a rare HCTD characterized by a deficiency in collagen lysyl hydroxylase 1 (LH1) due to mutations in PLOD1. […] Understanding the cellular and molecular mechanisms underlying JHS, particularly the involvement of membrane proteins, stands as a pivotal area of exploration. […] The quest for serum diagnostic markers through proteomic analysis marks a promising avenue, offering potential breakthroughs in JHS diagnosis.

• #6 Ehlers-Danlos Syndrome: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1114004-overview

  Ehlers-Danlos syndrome (EDS) is a heterogeneous group of inherited connective-tissue disorders characterized by joint hypermobility, cutaneous fragility, and hyperextensibility. The collagen defect has been identified in at least six of the many types of Ehlers-Danlos syndrome. […] The vascular form, sometimes referred to as type IV, is characterized by a decreased amount of type III collagen. It is autosomal dominant and caused by mutations in the COL3A1 gene that result in increased fragility of connective tissue with arterial, intestinal, and uterine ruptures and premature death. […] Types V and VI are characterized by deficiencies in hydroxylase and lysyl oxidase, an important posttranslational modifying enzyme in collagen biosynthesis. […] Type VII has an amino-terminal procollagen peptidase deficiency. Type IX has abnormal copper metabolism. Type X has nonfunctioning plasma fibronectin.

• #7 Hypermobility from a Mind Body perspective – Sirpa UK

  https://www.sirpa.org/hypermobility-from-a-mind-body-perspective/

  It is believed that hEDS is a genetic connective tissue disorder, one of 13 sub types of EDS, though NO gene has been identified. […] PoTS is known to be due to a dysfunction of the Autonomic Nervous System (ANS), but no clearer mechanism for the symptoms have been found by the scientific community. […] MCAS, PoTS and HSD/hEDS often occur in the same individual, but a common pathophysiological mechanism between any of the two has yet to be described. All three conditions remain controversial in either existence or understanding of the mechanism, and there is a lack of scientific evidence of the existence of MCAS, or hEDS as a separate or significant clinical entities. […] The immune system is closely linked with the ANS and when the body is stressed the immune system is suppressed, making one more susceptible to infections. This causes the body to become more responsive to external stimuli, creating the symptoms of MCAS. […] We know that chronic stress causes physiological changes in the body. SYMPTOMS ARE REAL, THEY ARE NOT JUST IN YOUR HEAD!!

• #8 hEDS & HSD Research: The Search for Causes and Diagnostic Tests – The Ehlers Danlos Society

  https://www.ehlers-danlos.com/heds-hsd-research/

  Hypermobile EDS (hEDS) remains the only type of the thirteen classified Ehlers-Danlos syndromes that cannot be confirmed through a genetic test. The genes associated with hEDS are currently unknown, and diagnosis is made on a clinical basis. […] Insights into the mechanisms that cause disease in hypermobile EDS (hEDS) remain scarce. An important reason for this is the huge variation in clinical presentation among hEDS patients, which makes it unlikely that a single genetic defect will be responsible to cause this condition, but at the same time, it also makes it hard to pinpoint the exact molecular cause. Nevertheless, given the overlap of clinical symptoms with other EDS subtypes, that lead to abnormalities in the extracellular matrix (ECM), especially with classical EDS (cEDS), it is likely that the mechanisms underlying hEDS also affect the ECM to a certain extent.

• #9 Joint Hypermobility Syndrome and Membrane Proteins: A Comprehensive Review

  https://www.mdpi.com/2218-273X/14/4/472

  Joint hypermobility syndrome (JHS) is a connective tissue disorder characterized by extreme flexibility of the joints, along with pain and other symptoms. […] The exact cause of JHS could be related to genetic changes in the proteins that add flexibility and strength to the joints, ligaments, and tendons, such as collagen. […] Recent studies have suggested that membrane proteins may also play a role in the pathogenesis of JHS. […] The integrin profile observed in EDS/HSD reveals a downregulation of the collagen receptor, α2β1 integrin, and the fibronectin receptor, α5β1 integrin, accompanied by an upregulation of the vitronectin receptor, αvβ3 integrin. […] This distinctive integrin expression pattern is coined the ‘integrin switch’, a phenomenon replicated in control cells through functional blocking of the α2β1 receptor.

• #10 Joint Hypermobility Syndrome and Membrane Proteins: A Comprehensive Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11048254/

  The absence of a structurally organized collagen in the ECM, preventing engagement with its receptor 21, results in the altered integrin expression profile. […] These findings propose that the commonality and defining characteristics among EDS/HSD subtypes may not lie in inherent defects in the structure or organization of collagen itself but rather in the adhesion of cells to collagen. […] Owing to their distinctive characteristics, membrane proteins exhibit significant potential as biomarkers. […] The strategic integration of these techniques not only enriches our understanding of the molecular landscape but also paves the way for establishing diagnostic modalities to decipher the pathogenesis of JHS. […] Understanding the cellular and molecular mechanisms underlying JHS, particularly the involvement of membrane proteins, stands as a pivotal area of exploration.

• #11 The role of cell adhesion and cytoskeleton dynamics in the pathogenesis of the Ehlers-Danlos syndromes and hypermobility spectrum disorders – WRAP: Warwick Research Archive Portal

  https://wrap.warwick.ac.uk/id/eprint/151120/

  The Ehlers-Danlos Syndromes (EDS) are a group of 13 disorders, clinically defined through features of joint hypermobility, skin hyperextensibility, and tissue fragility. […] The pathogenesis of all these disorders however, remains poorly understood. […] EDS/HSD fibroblasts exhibit a dysfunctional phenotype including impairments in cell adhesion and cytoskeleton organization, though the pathological significance of this has remained unclear. […] Recent advances in our understanding of fibroblast mechanobiology however, suggests these changes may actually reflect features of a pathomechanism we herein define. […] We propose that EDS/HSD may be a disorder of membrane-bound collagen, and consider how aberrations in cell adhesion and cytoskeletonal dynamics could drive the abnormal properties of the connective tissue, and may even be responsible for the pathogenesis of EDS/HSD.

• #12 Chronic pain in hypermobility syndrome and Ehlers–Danlos syndrom | JPR

  https://www.dovepress.com/chronic-pain-in-hypermobility-syndrome-and-ehlersndashdanlos-syndrome–peer-reviewed-fulltext-article-JPR

  Generalized joint hypermobility (GJH) is highly prevalent among patients diagnosed with chronic pain. When GJH is accompanied by pain in 4 joints over a period 3 months in the absence of other conditions that cause chronic pain, the hypermobility syndrome (HMS) may be diagnosed. […] Researchers and clinicians have struggled for decades with the highly diverse clinical presentation within the HMS and EDS-HT phenotypes and the lack of understanding of the pathological mechanisms that underlie the development of pain and its persistence. […] Despite recent scientific advances, many obstacles for clinical care and research still remain. […] The primary hypothesis regarding the development of musculoskeletal complaints is localized biomechanical overload during activity, with a high risk of repetitive trauma. Generalized joint instability may cause the occurrence of microtraumas on joint surfaces, leading to adaptation and compensation of movement patterns, consequently causing overload in other areas of the movement apparatus.

• #13 Chronic pain in hypermobility syndrome and Ehlers–Danlos syndrom | JPR

  https://www.dovepress.com/chronic-pain-in-hypermobility-syndrome-and-ehlersndashdanlos-syndrome–peer-reviewed-fulltext-article-JPR

  Although many theories have been proposed regarding why individuals with GJH develop chronic pain, no single pathophysiological model has been identified. […] Although evidence is inconclusive, it can be assumed that biomechanical factors do play a role in the pathological mechanism leading to the development of complaints. […] The presence of generalized hyperalgesia in adult patients with EDS-HT has been described recently. […] It was hypothesized that central-oriented upregulating processes are present within the central nervous system. […] The reasons for why upregulation of brain sensitivity does occur in patients with HMS and EDS-HT are unknown. […] The specific problems associated with the GJH-related syndromes, as compared to other chronic pain syndromes, are still challenging for most physicians and other health personnel due to many issues surrounding etiology, disease classification, diagnostics, and treatment.

• #14 Hypermobility spectrum disorders: A review

  https://www.degruyterbrill.com/document/doi/10.2478/rir-2023-0010/html?srsltid=AfmBOop-6LB4TSvgv23F3dmmKSQJVdoPujvnDuSNPiAMccOV4D4opc8X

  Patients with HSDs appear to lack proprioceptive acuity, which may increase risk of injury due to difficulty judging joint position. […] Beyond biomechanical factors, patients with HSDs may have neurologic perturbations that contribute to diffuse musculoskeletal pain. Generalized hyperalgesia is common and believed to be mediated by central sensitization. […] Knowledge about the pathophysiologic mechanisms that link HSDs to extra-articular manifestations is even less clear.

• #15 Dystonia in the joint hypermobility syndrome (a.k.a. Ehlers- Danlos syndrome, hypermobility type)

  https://symbiosisonlinepublishing.com/neurology/neurology23.php

  Ehlers-Danlos syndrome first described by Tschernogobow (1896) in Moscow and Ehlers (1900) in Copenhagen is a mostly autosomal inherited genetic disease of collagen synthesis that sensitizes the ensemble of the connective tissue which becomes less resistant and less elastic. […] Diagnosis of the hypermobile type of EDS is solely clinical as there is to date no genetic maker for the most frequent form of EDS. […] A great number of signs and symptoms have yet to be attributed to this syndrome. […] Dystonia plays an important part in the functional discomfort which is at the origin of a number of handicap situations. […] It seems to be related to dysautonomia common amongst the patients, proprioceptive problems and the multiple pains caused by the syndrome. […] We estimate that the alteration in proprioception plays a large part in the clinical manifestation of EDS.

• #16 The Effect of Joint Hypermobility Syndrome on DOMS and Recovery Time | Published in International Journal of Sports Physical Therapy

  https://ijspt.scholasticahq.com/article/91644-the-effect-of-joint-hypermobility-syndrome-on-doms-and-recovery-time

  JHS has been associated with many debilitating features including increased risk for injury, centralized fatigue, centralized pain, inhibition of surrounding muscles, and decreased strength/performance when compared to non-hypermobile individuals. Di Stefano et al. investigated how central sensitization could be the underlying mechanism causing pain in people with JHS and EDS. They stated that pain is a common symptom in patients with the connective tissue disorder, JHS, but the mechanism of why and how are unclear in previous studies. Their study included patients with JHS/EDS that participated in a detailed clinical exam to investigate the somatosensory nervous systems and central sensitization in this population. The authors discovered there was no damage to the somatosensory nervous system of these participants. However, they concluded that most of the subjects experienced widespread pain due to persistent nociceptive input due to joint abnormalities which probably triggers central sensitization in the dorsal horn neurons.

• #17 The Effect of Joint Hypermobility Syndrome on DOMS and Recovery Time | Published in International Journal of Sports Physical Therapy

  https://ijspt.scholasticahq.com/article/91644-the-effect-of-joint-hypermobility-syndrome-on-doms-and-recovery-time

  Igharno et al. compared the small fiber peripheral nerve fibers and autonomic nervous system of hypermobile EDS subjects to healthy controls. They confirmed that small nerve neuropathy and autonomic nervous dysfunction is a common feature of hypermobile EDS as an underlying pathomechanism of joint pain and dysfunction. […] The results of this study indicate that individuals with JHS may experience greater DOMS and require more time to recover between treatment sessions. Therapists need to be aware that hypermobile patients may experience higher pain levels, and so may need to adjust treatment parameters appropriately.

• #18 Dystonia in the joint hypermobility syndrome (a.k.a. Ehlers- Danlos syndrome, hypermobility type)

  https://symbiosisonlinepublishing.com/neurology/neurology23.php

  This receptor dysfunction is also a plausible explanation for the anarchy within the autonomic nervous system, especially the crises of tachycardia and hypotension due to a loss in reactivity of the carotid sinus receptors implanted in altered collagen. […] These observations suggest an intricate pathophysiological relationship between dystonia, dysautonomia and pain in Ehlers-Danlos syndrome which become the main therapeutic focus.

• #19 Joint hypermobility | Causes, symptoms, treatments

  https://versusarthritis.org/about-arthritis/conditions/joint-hypermobility/

  Hypermobility, however, can cause some people pain, fatigue, and injuries to joints and ligaments. […] The main cause of HSD and hEDS is genetics. Hypermobility often runs in families and therefore cannot be prevented. It is believed that if one parent has hypermobility one in two children will also have it. […] Someone who has HSD or hEDS often has faulty or weak collagen. Think of collagen as the glue that holds your entire body together, when this glue is faulty this can cause the ligaments to be weak or stretched so they don’t hold your joints as well. […] Research suggests that people with hypermobile joints may have weak collagen in other parts of the body as well, which can sometimes cause additional conditions or symptoms. […] Hypermobility can also cause digestive issues like gastroparesis, irritable bowel syndrome or gastric reflux. This can be due to the muscles that squeeze food through the digestive system being weak. This can lead to symptoms such as stomach pain, bloating, vomiting and constipation.

• #20 A narrative review of the literature on illness uncertainty in hypermobile ehlers-danlos syndrome: implications for research and clinical practice | Pediatric Rheumatology | Full Text

  https://ped-rheum.biomedcentral.com/articles/10.1186/s12969-023-00908-6

  Other challenges in early and accurate diagnosis can come from misattributions from health care professionals including concerns of child abuse/endangerment due to frequent injuries, subluxations and emergency department visits. […] While symptoms of hEDS should not be dismissed as somatic psychopathology symptoms, findings from the research surveyed suggests there are shared mechanisms underlying anxiety and symptoms of hEDS. […] Findings from the present review suggest that the adverse impact of IU in hEDS often reflect the unique facets of IU experienced by this population, as compared to the broader chronic pain population. […] High rates of anxiety disorders are noted in this population – generalized anxiety and panic disorders are noted in about 60-70% of hEDS patients, as well as an elevated risk of obsessive-compulsive personality disorder. […] Despite the notable impact of IU, it has been minimally studied in part due to the lack of validated measure for pediatric or adult hEDS.

• #21 A narrative review of the literature on illness uncertainty in hypermobile ehlers-danlos syndrome: implications for research and clinical practice | Pediatric Rheumatology | Full Text

  https://ped-rheum.biomedcentral.com/articles/10.1186/s12969-023-00908-6

  This perceived loss of control regarding ones illness and its treatment is defined as illness uncertainty (IU), and research has shown that IU is often associated with maladaptive coping, higher psychological distress, and reduced quality of life. […] While findings are robust in other disease populations, research within adults, and to an even greater extent, pediatric hEDS is sparse due in part to the lack of validated measure of this construct within this population. […] Therefore, consideration of the unique presentation and ramifications of IU in pediatric hEDS is crucial in order to provide a framework to guide the development of future clinical early intervention, given preliminary evidence of adverse effects of IU in hEDS more broadly. […] Current findings highlight the inconsistency of standards for diagnosis reported in the available literature, which reflect those used in clinical practice.

• #22 hEDS & HSD Research: The Search for Causes and Diagnostic Tests – The Ehlers Danlos Society

  https://www.ehlers-danlos.com/heds-hsd-research/

  The present proposal aims to unravel, by integrated molecular, biochemical/physical, and nanoscience approaches, bioactive key molecules, and pathophysiological mechanisms associated with these conditions. […] This research, followed by targeted in vivo translational studies on patients serum/plasma, should contribute to the elucidation of the etiopathogenesis of hEDS and HSD, offer the possibility to identify potential biomarkers defining whether these disorders are part of a phenotypic spectrum rather than distinct clinical entities and, ultimately, pave the way to the development of targeted therapeutic strategies with a potential benefit for patients management.

• #23 JOINT HYPERMOBILITY SYNDROME – RARELY RECOGNIZED PATHO…

  https://kwartalnikortopedyczny.publisherspanel.com/article/01.3001.0008.8370/en

  Joint hypermobility syndrome (JHS) is a term denoting symptomatic defect of connective tissue manifested by pain associated with increased above the norm for sex and age range of motion in joints. […] The study describes the problem of JHS epidemiology, currently used diagnostic criteria, pathogenesis and clinical picture of the syndrome. […] Prevention and treatment modalities of the pathology are also presented.

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