Ehlers-Danlos Treatment Report

www.EhlersDanlosTreatmentReport.com

Research

Pain Symptomatology and Management in Pediatric Ehlers-Danlos Syndrome: A Review

https://www.mdpi.com/2227-9067/7/9/146/htm

https://www.ncbi.nlm.nih.gov/pubmed/32967103?dopt=Abstract

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Pain Symptomatology and Management in Pediatric Ehlers-Danlos Syndrome: A Review.

Children (Basel). 2020 Sep 21;7(9):

Authors: Feldman ECH, Hivick DP, Slepian PM, Tran ST, Chopra P, Greenley RN

Abstract

Ehlers-Danlos syndromes (EDS) are a group of connective tissue disorders that manifest with hyperextensibility of joints and skin, and general tissue fragility. While not a major criterion for clinical diagnosis, pain is a frequently endorsed symptom across subtypes of EDS. As such, the present review aims to summarize research to date on pain characteristics and management, and the relationship between such pain symptomatology and quality of life in pediatric EDS. Characteristics of pain, including theorized etiology, relative intensity and extent of pain are described, as well as descriptions of frequently endorsed pain sites (musculoskeletal, and non-musculoskeletal). Interventions related to the management of musculoskeletal (e.g., pharmaceutical intervention, physical therapy) and non-musculoskeletal pain (e.g., pharmaceutical and psychological interventions) are discussed, highlighting the need for additional research related to pediatric pain management in the context of hypermobility syndromes. In addition, the relationship between pain in pediatric EDS and quality of life is described. Finally, limitations of literature to date are described and recommendations for future lines of research are outlined.

PMID: 32967103 [PubMed]

Headaches in hypermobility syndromes: A pain in the neck?

https://www.ncbi.nlm.nih.gov/pubmed/32940405?dopt=Abstract

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Headaches in hypermobility syndromes: A pain in the neck?

Am J Med Genet A. 2020 Sep 17;:

Authors: Malhotra A, Pace A, Ruiz Maya T, Colman R, Gelb BD, Mehta L, Kontorovich AR

Abstract

Headache and neck pain (cervicalgia) are frequently reported among patients with joint hypermobility but the prevalence and scope of these symptoms has not been studied in the era of contemporary Ehlers-Danlos and hypermobility disorder nosology. We performed a single-center retrospective study on the incidence of head and neck symptoms in 140 patients with hypermobility disorders over a 2-year period. Overall, 93 patients (66%) reported either headache or neck pain with 49 of those (53%) reporting both. Migraine (83%) was the most common headache type among those with headache disorders and cervical spondylosis (61%) the most common pathology among those with neck symptoms. Fifty-nine percent of spondylosis patients who underwent cervical facet procedures reported significant improvement in neck and head symptoms. Of patients with both head and neck complaints, 82% had both migraine and spondylosis, which, when combined with the high response rate to injections raises the possibility of cervicogenic headache. In this large multidisciplinary retrospective study of patients with hypermobility disorders, head and neck symptoms were highly prevalent, with migraine and cervical spondylosis common, often coexisting, and frequently responsive to targeted therapy for the cervical spine suggesting that degenerative spinal pathology may cause or contribute to headache symptoms in some patients with hypermobility disorders.

PMID: 32940405 [PubMed – as supplied by publisher]

Current management of the vascular subtype of Ehlers-Danlos syndrome

https://journals.lww.com/co-cardiology/Abstract/9000/Current_management_of_the_vascular_subtype_of.98958.aspx

https://www.ncbi.nlm.nih.gov/pubmed/32941194?dopt=Abstract

Current management of the vascular subtype of Ehlers-Danlos syndrome.

Curr Opin Cardiol. 2020 Sep 15;:

Authors: Benrashid E, Ohman JW

Abstract

PURPOSE OF REVIEW: Vascular Ehlers-Danlos syndrome (vEDS) is the most severe form of EDS, affecting the synthesis of type III collagen. It is notable for decreased life expectancy and morbidity, including spontaneous vessel rupture. The present review summarizes recent findings that have improved the ability to manage and delineate the natural history of vEDS.

RECENT FINDINGS: Recent EDS consortium guidelines for the diagnosis of vEDS have emerged and outlined clinical features and molecular diagnostic tools to help facilitate rapid diagnosis. Although medical interventions to help halt the disease progression remain limited, improved awareness of vEDS by patients and practitioners have resulted in increased average life expectancy. Early excitement with celiprolol has been tempered by a lack of high-quality studies. Likewise, the creation of multidisciplinary care teams and tertiary referral centers is helping improve outcomes. Unfortunately, there remain limitations in terms of the surgical management (including more advanced endovascular techniques) of these patients and the morbidity associated with these interventions.

SUMMARY: Although new consensus guidelines have emerged to facilitate the diagnosis of those with vEDS, there remain limitations in terms of interventions and medical therapy that can be provided for these patients. Life expectancy does appear to be improving however with increased awareness and coordinated multidisciplinary efforts among medical geneticists, general practitioners, and interventionalists alike.

PMID: 32941194 [PubMed – as supplied by publisher]

Use of complementary therapies for chronic pain management in patients with reported Ehlers-Danlos syndrome or hypermobility spectrum disorders

https://pubmed.ncbi.nlm.nih.gov/32909698/

https://www.ncbi.nlm.nih.gov/pubmed/32909698?dopt=Abstract

Use of complementary therapies for chronic pain management in patients with reported Ehlers-Danlos syndrome or hypermobility spectrum disorders.

Am J Med Genet A. 2020 Sep 10;:

Authors: Demes JS, McNair B, Taylor MRG

Abstract

Ehlers-Danlos Syndromes (EDS) and related Hypermobility Spectrum Disorders (HSD) are debilitating connective tissue disorders that feature a prominent pain component for which there are limited therapeutic options for pain management. Consequently, many patients try various non-prescribed treatments, including complementary and alternative therapies that have not been well studied in the EDS/HSD patient population. We surveyed over 500 individuals through the EDS Society who reported having been diagnosed with EDS or HSD to ascertain what complementary and alternative therapies were used and their reported effectiveness in alleviating pain and improving quality of life. Specifically, we focused on the use of traditional Chinese therapies, herbal medications, and marijuana. The most commonly reported therapies, used by 70-92% of participants, were non-steroidal anti-inflammatory drugs, acetaminophen, opioids, and physical therapy. Therapies rated by participants as most efficacious were opioids, physical therapy, and marijuana with 10-24% of those using these therapies rating them as extremely helpful. Patient-initiated complementary therapy use in EDS/HSD patients is widespread at 56%. Complementary therapies were largely utilized by EDS/HSD patients with higher reported pain levels. Providers caring for EDS/HSD patients should be aware of these data showing broad usage of predominantly non-prescribed therapies and be prepared to consider such usage in working collaboratively with these patients to develop comprehensive treatment plans to manage their chronic pain complications.

PMID: 32909698 [PubMed – as supplied by publisher]

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Co-Segregation of Postural Orthostatic Tachycardia Syndrome, Hypermobile Ehlers-Danlos Syndrome and Mast Cell Activation Syndrome

https://www.annallergy.org/article/S1081-1206(20)30571-8/fulltext

Co-Segregation of Postural Orthostatic Tachycardia Syndrome, Hypermobile Ehlers-Danlos Syndrome and Mast Cell Activation Syndrome
Peter Vadas, MD PhD
Juan Guzman, MD
Laura McGillis, MN, RN(EC)
Nimish Mittal, MD
Scott Walsh, MD
Published:August 13, 2020DOI:https://doi.org/10.1016/j.anai.2020.08.015
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Mast cell activation syndrome presents with signs and symptoms attributed to release of mast cell-derived mediators, without evidence of primary or secondary diseases associated with mast cell activation. The manifestations result from the mast cells mediator release, with symptoms affecting multiple organ systems 1 . Therapy is directed to suppression of symptoms using receptor antagonists and mast cell stabilizers 2 . The diagnosis of MCAS is based on the presence of (i) validated symptoms of mast cell activation; (ii) elevated serum or urinary markers of mast cell activation and (iii) an appropriate therapeutic response to anti-mediatory therapy 3 . MCAS has been shown to be associated with POTS 4 . Several studies have pointed to a connection between POTS and EDS 5 , 6 . There is considerable overlap between symptoms associated with POTS and MCAS, including flushing, hypotension and diarrhea 4 such that the contribution of each condition to a patient’s symptoms may be unclear. Herein, we set out to characterize patients with MCAS and co-existent POTS and hEDS/HSD.

Ehlers-Danlos Syndrome: An Analysis of the Current Treatment Options for Pain and Symptom Relief

https://www.painphysicianjournal.com/linkout?issn=&vol=23&page=429

https://www.ncbi.nlm.nih.gov/pubmed/32709178?dopt=Abstract

Related Articles

Ehlers-Danlos Syndrome: An Analysis of the Current Treatment Options.

Pain Physician. 2020 Jul;23(4):429-438

Authors: Song B, Yeh P, Nguyen D, Ikpeama U, Epstein M, Harrell J

Abstract

BACKGROUND: Ehlers-Danlos syndrome (EDS) is a multifaceted disease that can present with a variety of types of pain. Unfortunately, both the mechanisms and treatments for pain are poorly understood. The proposed treatments for the various musculoskeletal pain syndromes in EDS have had variable success, and it becomes much more imperative to better define and evaluate the current treatment modalities in treating this debilitating disease.

OBJECTIVES: The purpose of this study was to investigate the currently available treatment modalities for patients with EDS and their efficacies in pain and symptom relief.

STUDY DESIGN: Retrospective cohort study.

SETTING: Institutional physical medicine and rehabilitation primary care clinic.

METHODS: All patients were seen between January 2015 and April 2019, in which 98 patients with EDS were identified through retrospective chart review. Institutional review board approval was obtained, and all patients provided written consent to be included in the study. We reviewed various treatment modalities, including complimentary/alternative treatments, opioids/opioid-like medications, nonsteroidal antiinflammatory drugs, physical therapy, occupational therapy, muscle relaxants, neuropathic modulators, steroids, surgery/procedures, and acetaminophen. Treatment methods were extracted from individual patient charts, and efficacy was grouped into 3 categories: improvement, no effect, or worsened symptoms.

RESULTS: The most common treatments used were complimentary/alternative treatments (n = 88). Occupational therapy and bracing were the most effective options with 70% of patients reporting improvement. Neuropathic modulators were the least well tolerated with 47% of patients reporting adverse effects.

LIMITATIONS: Men were a small percentage of the study. Patients were not randomized, and pain score reporting was subjective. Patient data were extracted from a single practice setting. Timing and symptom onset were not measured.

CONCLUSIONS: There is a relative paucity of published literature regarding the various treatment methods for EDS. Although our study is able to identify positive and negative trends with certain modalities, it is vital to understand that EDS is not a uniform diagnosis among patients, and that a combination of several different treatments usually is needed for optimal symptom control. Further research and investigation are necessary to develop a comprehensive treatment database for this complex condition.

KEY WORDS: Ehlers-Danlos syndrome, pain, hypermobility, arthralgia, subluxation, genetic, physical therapy, interventional pain.

PMID: 32709178 [PubMed – in process]

The First Experience of Denosmab Therapy on Patients with Ehlers-Danlos Syndrome and Osteoporosis

https://www.tandfonline.com/doi/abs/10.1080/24725625.2020.1799493?journalCode=tmcr20

https://www.ncbi.nlm.nih.gov/pubmed/32692295?dopt=Abstract

Related Articles

The First Experience of Denosmab Therapy on Patients with Ehlers-Danlos Syndrome and Osteoporosis: Detailed Observation of Two Patients.

Mod Rheumatol Case Rep. 2020 Jul 21;:1-14

Authors: Yasukawa S, Uehara M, Suzuki T, Nakano M, Kosho T, Nakamura Y, Takahashi J

Abstract

Background: Previous studies have shown decreased bone mineral density (BMD) due to an unknown mechanism in Ehlers-Danlos Syndrome (EDS) patients and described approaches to treatment for osteoporosis in EDS. To date, however, there is no established method of treatment. In this study, we investigated two patients with EDS to clarify the efficacy and safety of denosumab treatment in EDS patients with osteoporosis.Methods: We retrospectively enrolled two EDS patients with osteoporosis who underwent denosumab therapy.Results: Patient 1 was a 59-year-old male with classical EDS and osteoporosis who received a 48-month course of denosumab therapy. His lumbar BMD and total hip BMD were 1.335 g/cm2 and 0.762 g/cm2 before treatment, respectively. Forty-eight months later, the lumbar and total hip BMD showed gains of 1.6% and 11.4%, respectively.Patient 2 was a 42-year-old male with vascular EDS and osteoporosis who received an 18-month course of denosumab therapy. His lumbar BMD and total hip BMD were 0.763 g/cm2 and 0.583 g/cm2 before treatment, respectively. Eighteen months later, the lumbar and total hip BMD showed gains of 5.0% and 1.8%, respectively. No fractures or other complications were recorded during the observational period in both cases.Conclusions: This is the first experience of denosmab therapy on patients with EDS and osteoporosis. Denosumab, administered safely with no serious adverse effects such as fractures, exerted a fluctuating but probably positive effect regarding BMD and could be a treatment option on these patients.

PMID: 32692295 [PubMed – as supplied by publisher]

The effectiveness of conservative interventions for the management of syndromic hypermobility: a systematic literature review

https://link.springer.com/article/10.1007%2Fs10067-020-05284-0

https://www.ncbi.nlm.nih.gov/pubmed/32681365?dopt=Abstract

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The effectiveness of conservative interventions for the management of syndromic hypermobility: a systematic literature review.

Clin Rheumatol. 2020 Jul 17;:

Authors: Palmer S, Davey I, Oliver L, Preece A, Sowerby L, House S

Abstract

INTRODUCTION: ‘Syndromic hypermobility’ encompasses heritable connective tissue disorders such as hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorders which are characterised by excessive joint range of motion and pain. Conservative interventions such as exercise are the cornerstone of management, yet their effectiveness is unclear.

AIM: To systematically appraise the effectiveness of conservative management for people with syndromic hypermobility.

METHOD: A systematic online database search was conducted (AMED, BND, CINAHL Plus, MEDLINE, PEDro, PsychINFO and SportDiscus). Potential articles were assessed for eligibility by two researchers against the following criteria: adults and children with a hEDS/HSD diagnosis (or equivalent diagnosis using specific criteria); non-pharmacological or non-surgical interventions; outcomes related to pain, physical function, psychological well-being or quality of life. Controlled trials and cohort studies were included. Critical Appraisal Skills Programme checklists were used to assess methodological quality.

RESULTS: Eleven studies were included, comprising eight controlled trials and three cohort studies. All studies investigated interventions that had exercise as the primary component. Three small controlled studies demonstrated superior effects of conservative management relative to a control group. However, those studies only focused on a single area of the body, only recruited women, and had no long-term follow-up. All studies reported improvements in a wide range of outcomes over time.

CONCLUSION: Controlled trial evidence for the superiority of conservative management over comparators is weak. There is some evidence that people improve over time. Robust randomised controlled trial research of the long-term effectiveness of ‘whole-body’ (rather than individual joints or body areas) conservative management is required. Key Points • Conservative management is the cornerstone of management of syndromic hypermobility. • The review found that evidence for the effectiveness of conservative management relative to no treatment or other conservative comparators was weak. • However, there was consistent evidence for effectiveness from pre- to post-treatment. • Further robust randomised controlled trial evidence is required.

PMID: 32681365 [PubMed – as supplied by publisher]

Hypermobile Ehlers-Danlos Syndromes: Complex Phenotypes, Challenging Diagnoses and Poorly Understood Causes [PDF]

https://anatomypubs.onlinelibrary.wiley.com/doi/epdf/10.1002/dvdy.220

https://pubmed.ncbi.nlm.nih.gov/32629534/

Review Dev Dyn
2020 Jul 6. doi: 10.1002/dvdy.220. Online ahead of print.

Hypermobile Ehlers-Danlos Syndromes: Complex Phenotypes, Challenging Diagnoses and Poorly Understood Causes

Cortney Gensemer 1, Randall Burks 1, Steven Kautz 2, Daniel P Judge 3, Mark Lavallee 4, Russell A Norris 1
Affiliations expand
PMID: 32629534 DOI: 10.1002/dvdy.220
Abstract
The Ehlers Danlos Syndromes (EDS) are a group of heritable, connective tissue disorders characterized by joint hypermobility, skin hyperextensibility and tissue fragility. There is phenotypic and genetic variation among the thirteen subtypes. The initial genetic findings on EDS were related to alterations in fibrillar collagen, but the elucidation of the molecular basis of many of the subtypes revealed several genes not involved in collagen biosynthesis or structure. However, the genetic basis of the hypermobile type of EDS (hEDS) is still unknown. hEDS is the most common type of EDS and involves generalized joint hypermobility, musculoskeletal manifestations, and mild skin involvement along with the presence of several co-morbid conditions. Variability in the spectrum and severity of symptoms and progression of patient phenotype likely depend on age, gender, lifestyle and expression domains of the EDS genes during development and postnatal life. In this review, we summarize the current molecular, genetic, epidemiologic and pathogenetic findings related to Ehlers-Danlos Syndromes with a focus on the hypermobile type. This article is protected by copyright.

Skin fragility in musculocontractural Ehlers-Danlos syndrome caused by CHST14 variants (mcEDS-CHST14): the role of dermatan sulfate in maintaining skin strength

https://academic.oup.com/glycob/article-abstract/doi/10.1093/glycob/cwaa058/5863922?redirectedFrom=fulltext

https://www.ncbi.nlm.nih.gov/pubmed/32601684?dopt=Abstract

skin fragility of patients with mcEDS-CHST14, shedding light on the role of dermatan sulfate in maintaining skin strength

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Systematic investigation of the skin in Chst14-/- mice: a model for skin fragility in musculocontractural Ehlers-Danlos syndrome caused by CHST14 variants (mcEDS-CHST14).

Glycobiology. 2020 Jun 27;:

Authors: Hirose T, Mizumoto S, Hashimoto A, Takahashi Y, Yoshizawa T, Nitahara-Kasahara Y, Takahashi N, Nakayama J, Takehana K, Okada T, Nomura Y, Yamada S, Kosho T, Watanabe T

Abstract

Loss-of-function variants in CHST14 cause a dermatan 4-O-sulfotransferase deficiency named musculocontractural Ehlers-Danlos syndrome-CHST14 (mcEDS-CHST14), resulting in complete depletion of the dermatan sulfate moiety of decorin glycosaminoglycan (GAG) chains, which is replaced by chondroitin sulfate. Recently, we uncovered structural alteration of GAG chains in the skin of patients with mcEDS-CHST14. Here, we conducted the first systematic investigation of Chst14 gene-deleted homozygote (Chst14-/-) mice. We used skin samples of wild-type (Chst14+/+) and Chst14-/- mice. Mechanical fragility of the skin was measured with a tensile test. Pathology was observed using light microscopy, decorin immunohistochemistry, and electron microscopy (EM) including cupromeronic blue (CB) staining. Quantification of chondroitin sulfate and dermatan sulfate was performed using enzymatic digestion followed by anion-exchange HPLC. In Chst14-/- mice, skin tensile strength was significantly decreased compared with that in Chst14+/+ mice. EM showed that collagen fibrils were oriented in various directions to form disorganized collagen fibers in the reticular layer. Through EM-based CB staining, rod-shaped linear GAG chains were found to be attached at one end to collagen fibrils and protruded outside of the fibrils, in contrast to them being round and wrapping the collagen fibrils in Chst14+/+ mice. A very low level of dermatan sulfate disaccharides was detected in the skin of Chst14-/- mice by anion-exchange chromatography. Chst14-/- mice, exhibiting similar abnormalities in the GAG structure of decorin and collagen networks in the skin, could be a reasonable model for skin fragility of patients with mcEDS-CHST14, shedding light on the role of dermatan sulfate in maintaining skin strength.

PMID: 32601684 [PubMed – as supplied by publisher]

A new insight on postural tachycardia syndrome in adults with hypermobile Ehlers-Danlos Syndrome/hypermobility spectrum disorder [PDF]

https://www.monaldi-archives.org/index.php/macd/article/view/1286/1022

https://www.monaldi-archives.org/index.php/macd/article/view/1286

https://pubmed.ncbi.nlm.nih.gov/32434316/

https://doi.org/10.4081/monaldi.2020.1286

A new insight on postural tachycardia syndrome in 102 adults with hypermobile Ehlers-Danlos Syndrome/hypermobility spectrum disorder

Effects of Rhythmic Sensory Stimulation delivered using a Vibroacoustic Device on Ehlers-Danlos Syndrome

https://www.hindawi.com/journals/prm/2020/3586767/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7204284/

https://www.ncbi.nlm.nih.gov/pubmed/32399126?dopt=Abstract

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Effects of Rhythmic Sensory Stimulation on Ehlers-Danlos Syndrome: A Pilot Study.

Pain Res Manag. 2020;2020:3586767

Authors: Vuong V, Mosabbir A, Paneduro D, Picard L, Faghfoury H, Evans M, Gordon A, Bartel L

Abstract

Ehlers-Danlos syndrome (EDS) is a connective tissue disorder characterized by joint hypermobility and skin extensibility and is often accompanied by chronic pain. Rhythmic sensory stimulation (RSS) can be defined as the stimulation of the senses in a periodic manner within a range of low frequencies. Music plus sound delivered through a vibroacoustic device is a form of RSS and has demonstrated utility in managing pain. In this current study, we conducted an open-label pilot study of 15 patients with hypermobile EDS using RSS as the intervention. Posttreatment improvements were seen in 11 of the 15 patients (73%), whereas 3 of the 15 patients (20%) experienced worse outcomes. Of the 14 patients that completed the experiment, 6 participants (43%) were classified as “responders” to the device while 8 participants (57%) were classified as “nonresponders.” Responders demonstrated significant improvements in pain interference (51.5 ± 16 preintervention vs. 43.5 ± 16.4 postintervention BPI score) and depression symptoms (34.0 ± 15.9 preintervention vs. 26.8 ± 12.1 postintervention CESD score). Poststudy interviews confirm the improvements of pain interference, mood, and bowel symptoms. Furthermore, analysis of medical conditions within the responder group indicates that the presence of depression, anxiety, irritable bowel syndrome, and fibromyalgia may indicate a greater likelihood for patients to benefit with vibroacoustic applications. These results indicate a possible potential for RSS, delivered using a vibroacoustic device, in managing pain-related symptoms. Further research is necessary to elucidate the exact mechanism behind the physiological benefits of RSS.

PMID: 32399126 [PubMed – in process]

Pain due to Ehlers-Danlos Syndrome Is Associated with Deficit of the Endogenous Pain Inhibitory Control

https://academic.oup.com/painmedicine/advance-article-abstract/doi/10.1093/pm/pnaa038/5807603?redirectedFrom=fulltext

https://www.ncbi.nlm.nih.gov/pubmed/32176287?dopt=Abstract

Related Articles

Pain due to Ehlers-Danlos Syndrome Is Associated with Deficit of the Endogenous Pain Inhibitory Control.

Pain Med. 2020 Mar 16;:

Authors: Leone CM, Celletti C, Gaudiano G, Puglisi PA, Fasolino A, Cruccu G, Camerota F, Truini A

Abstract

OBJECTIVES: Although pain is a common complication of the hypermobile type of Ehlers-Danlos syndrome, its underlying mechanisms are still an issue of controversy. In this psychophysical study, we aimed at testing small-fiber function and the endogenous pain inhibitory control in patients with pain due to Ehlers-Danlos syndrome.

METHODS: In 22 patients with pain due to Ehlers-Danlos syndrome and 22 healthy participants, matched for age and sex, we tested small-fiber function using quantitative sensory testing and the endogenous pain inhibitory control using the conditioned pain modulation (CPM) protocol. As quantitative sensory testing methods, we included thermal pain and mechanical pain thresholds and the wind-up ratio. The CPM protocol consisted of two heat painful stimuli, that is, a test stimulus and a conditioning stimulus.

RESULTS: All patients complained of widespread pain. Quantitative sensory testing revealed no small-fiber deficit; in the area of maximum pain, we found an increased wind-up ratio. Whereas in the healthy participants the CPM protocol showed that the test stimulus rating was significantly reduced during conditioning, in patients with pain due to hEDS, the test stimulus rating increased during conditioning.

CONCLUSIONS: Our psychophysical study showing that patients with pain due to hEDS have an increased wind-up ratio in the area of maximum pain and abnormal CPM protocol suggests that in this condition, pain is associated with central sensitization, possibly due to deficit of the endogenous pain inhibitory control. These data might be relevant to pharmacological treatment.

PMID: 32176287 [PubMed – as supplied by publisher]

Clinical features, molecular results, and management of individuals with arthrochalasia Ehlers-Danlos syndrome (aEDS)

https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.a.61523

https://www.ncbi.nlm.nih.gov/pubmed/32091183?dopt=Abstract

Clinical features, molecular results, and management of 12 individuals with the rare arthrochalasia Ehlers-Danlos syndrome.

Am J Med Genet A. 2020 Feb 24;:

Authors: Ayoub S, Ghali N, Angwin C, Baker D, Baffini S, Brady AF, Giovannucci Uzielli ML, Giunta C, Johnson DS, Kosho T, Neas K, Pope FM, Rutsch F, Scarselli G, Sobey G, Vandersteen A, van Dijk FS

Abstract

Arthrochalasia Ehlers-Danlos syndrome (aEDS) is a rare autosomal dominant connective tissue disorder that is characterized by congenital bilateral hip dislocations, severe generalized joint hypermobility, recurrent joint (sub)luxations, and skin hyperextensibility. To date, 42 patients with aEDS have been published. We report 12 patients with aEDS from 10 families with 6 unpublished individuals and follow-up data on 6 adult patients. The clinical features are largely comparable with patients reported in the literature. Most (n = 10) patients had variants leading to (partial) loss of exon 6 of the COL1A1 or COL1A2 genes. One patient did not have a previously reported likely pathogenic COL1A1 variant. Data regarding management were retrieved. Hip surgery was performed in 5/12 patients and 3/12 patients underwent spinal surgery. As much as 4/12 patients were wheelchair-bound or unable to walk unaided. Fractures were present in 9/12 individuals with 1 patient requiring bisphosphonate treatment. Echocardiograms were performed in 10 patients and 2 individuals showed an abnormality likely unrelated to aEDS. One patient gave birth to two affected children and went through preterm labor requiring medication but had no additional complications. Of the seven adults in our cohort, the majority entered a career. Our data point toward a genotype-phenotype relationship with individuals with aEDS due to pathogenic COL1A1 variants causing complete or partial loss of exon 6 being more severely affected regarding musculoskeletal features. There is a significant lack of knowledge with regard to management of aEDS, particularly in adulthood. As such, systematic follow-up and multidisciplinary treatment is essential.

PMID: 32091183 [PubMed – as supplied by publisher]

Custom-Made Foot Orthoses Reduce Pain and Fatigue in Patients with Ehlers-Danlos Syndrome. A Pilot Study

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068607/

https://www.ncbi.nlm.nih.gov/pubmed/32093191?dopt=Abstract

Related Articles

Custom-Made Foot Orthoses Reduce Pain and Fatigue in Patients with Ehlers-Danlos Syndrome. A Pilot Study.

Int J Environ Res Public Health. 2020 02 20;17(4):

Authors: Reina-Bueno M, Vázquez-Bautista C, Palomo-Toucedo IC, Domínguez-Maldonado G, Castillo-López JM, Munuera-Martínez PV

Abstract

BACKGROUND: Pain and fatigue are major clinical manifestations in patients with Ehlers-Danlos Syndrome (EDS). The aim of this study is to measure change of the effects of custom-made foot orthotics on some manifestations related to EDS, such as foot pain, foot functionality, fatigue, and quality of life.

METHODS: Thirty-six patients with EDS wore foot orthoses for three months. Foot pain, foot-related disability, foot functionality, fatigue, and quality of life were measured using the 11-point Numeric Rating Scale, the Manchester Foot Pain and Disability Index, the Foot Function Index, the Fatigue Severity Score, and the 12-Item Short Form Health Survey questionnaires, respectively, at the beginning and after 3 months.

RESULTS: Participants demonstrated significantly improved foot pain (p = 0.002), disability related to foot pain (p < 0.001), foot functionality (p = 0.001), fatigue (p < 0.007), and mental health-related quality of life (p = 0.016). The physical health-related quality of life did not show significant changes. CONCLUSIONS: The use of custom-made foot orthoses help in the management of the symptoms by participants. This study could contribute to the foot specialists being considered as an additional member in multidisciplinary teams that are trying to develop an approach for patients with EDS. PMID: 32093191 [PubMed - indexed for MEDLINE]

An old drug for a rare disease: The example of celiprolol for vascular Ehlers-Danlos syndrome

https://www.sciencedirect.com/science/article/pii/S0040595720300147?via%3Dihu

https://www.ncbi.nlm.nih.gov/pubmed/32127191?dopt=Abstract

Related Articles

An old drug for a rare disease: The example of celiprolol for vascular Ehlers-Danlos syndrome.

Therapie. 2020 Feb 13;:

Authors: Boutouyrie P

Abstract

Vascular Ehlers-Danlos syndrome (OMIM 130050, 1/150,000 birth) is caused by mutations in collagen 3A1 gene. It is associated with severe phenotype associating early arterial dissection and rupture, digestive and uterine perforations, and skin and joints fragility. Until recently, no treatment was available. Celiprolol, a beta1 antagonist with beta2 partial antagonist properties betablocker was tested in a randomized, controlled trial. We could show that this compound was associated with a 3-fold decrease in major events related to the disease. This effect was similar in molecular-proven patients. Administration of celiprolol in a cohort of patients followed routinely in France was accompanied to similar benefit. Celiprolol is unavailable in the USA. The ACER Therapeutics company applied for new drug application (NDA) to the Food and Drug Administration.

PMID: 32127191 [PubMed – as supplied by publisher]

Arterial Elasticity in Ehlers-Danlos Syndromes: a possible explanation for the common presence of Orthostatic Intolerance (OI) in all EDS types

https://www.mdpi.com/2073-4425/11/1/55/htm

Arterial Elasticity in Ehlers-Danlos Syndromes

Arterial Elasticity in Ehlers-Danlos Syndromes: a possible explanation for the common presence of Orthostatic Intolerance (OI) in all EDS types

by Amanda J. Miller ,Jane R. Schubart ,Timothy Sheehan ,Rebecca Bascom andClair A. Francomano
Genes 2020, 11(1), 55; https://doi.org/10.3390/genes11010055 – 04 Jan 2020

Abstract: Ehlers-Danlos Syndromes (EDS) are a group of heritable disorders of connective tissue (HDCT) characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Orthostatic intolerance (OI) is highly prevalent in EDS however mechanisms linking OI to EDS remain poorly understood. We hypothesize that impaired blood pressure (BP) and heart rate control is associated with lower arterial stiffness in people with EDS. Orthostatic vital signs and arterial stiffness were assessed in a cohort of 60 people with EDS (49 female, 36 ± 16 years). Arterial elasticity was assessed by central and peripheral pulse wave velocity (PWV). Central PWV was lower in people with EDS compared to reference values in healthy subjects. In participants with EDS, central PWV was correlated to supine systolic BP (r = 0.387, p = 0.002), supine diastolic BP (r = 0.400, p = 0.002), and seated systolic BP (r = 0.399, p = 0.002). There were no significant correlations between PWV and changes in BP or heart rate with standing (p > 0.05). Between EDS types, there were no differences in supine hemodynamics or PWV measures (p > 0.05). These data demonstrate that increased arterial elasticity is associated with lower BP in people with EDS which may contribute to orthostatic symptoms and potentially provides a quantitative clinical measure for future genotype-phenotype investigations.
Keywords: Ehlers-Danlos syndromes; pulse wave velocity; blood pressure; orthostatic intolerance

The Many Facets of Hypermobile Ehlers-Danlos Syndrome

https://pubmed.ncbi.nlm.nih.gov/31904772-the-many-facets-of-hypermobile-ehlers-danlos-syndrome/

https://jaoa.org/article.aspx?articleid=2758542

The Many Facets of Hypermobile Ehlers-Danlos Syndrome

Bernadette Riley, DO, Ehlers-Danlos Syndrome/Hypermobility Treatment Center, Department of Family Medicine, New York Institute of Technology College of Osteopathic Medicine, Northern Blvd, Old Westbury, NY, 11568-8000. Email: briley@nyit.edu

The Journal of the American Osteopathic Association, January 2020, Vol. 120, 30-32. doi:https://doi.org/10.7556/jaoa.2020.012

Recent Advances in the Pathophysiology of Musculocontractural Ehlers-Danlos Syndrome

https://www.mdpi.com/2073-4425/11/1/43

https://pubmed.ncbi.nlm.nih.gov/31905796-recent-advances-in-the-pathophysiology-of-musculocontractural-ehlers-danlos-syndrome/

Recent Advances in the Pathophysiology of Musculocontractural Ehlers-Danlos Syndrome

Abstract

Musculocontractural Ehlers-Danlos Syndome (mcEDS) is a type of EDS caused by biallelic pathogenic variants in the gene for carbohydrate sulfotransferase 14/dermatan 4-O-sulfotransferase 1 (CHST14/D4ST1, mcEDS-CHST14), or in the gene for dermatan sulfate epimerase (DSE, mcEDS-DSE). Thus far, 41 patients from 28 families with mcEDS-CHST14 and five patients from four families with mcEDS-DSE have been described in the literature. Clinical features comprise multisystem congenital malformations and progressive connective tissue fragility-related manifestations. This review outlines recent advances in understanding the pathophysiology of mcEDS. Pathogenic variants in CHST14 or DSE lead to reduced activities of relevant enzymes, resulting in a negligible amount of dermatan sulfate (DS) and an excessive amount of chondroitin sulfate. Connective tissue fragility is presumably attributable to a compositional change in the glycosaminoglycan chains of decorin, a major DS-proteoglycan in the skin that contributes to collagen fibril assembly. Collagen fibrils in affected skin are dispersed in the papillary to reticular dermis, whereas those in normal skin are regularly and tightly assembled. Glycosaminoglycan chains are linear in affected skin, stretching from the outer surface of collagen fibrils to adjacent fibrils; glycosaminoglycan chains are curved in normal skin, maintaining close contact with attached collagen fibrils. Homozygous (Chst14-/-) mice have been shown perinatal lethality, shorter fetal length and vessel-related placental abnormalities. Milder phenotypes in mcEDS-DSE might be related to a smaller fraction of decorin DS, potentially through residual DSE activity or compensation by DSE2 activity. These findings suggest critical roles of DS and DS-proteoglycans in the multisystem development and maintenance of connective tissues, and provide fundamental evidence to support future etiology-based therapies.

Keywords: CHST14; DSE; carbohydrate sulfotransferase-14 (CHST14)/dermatan 4-O-sulfotransferase-1 (D4ST1); collagen; decorin; dermatan sulfate (DS); dermatan sulfate epimerase (DSE); musculocontractural Ehlers–Danlos Syndome.

Hypomorphic zebrafish models mimic the musculoskeletal phenotype of β4GalT7-deficient Ehlers-Danlos syndrome

https://www.sciencedirect.com/science/article/pii/S0945053X19304007?via%3Dihub

https://pubmed.ncbi.nlm.nih.gov/31862401-hypomorphic-zebrafish-models-mimic-the-musculoskeletal-phenotype-of-4galt7-deficient-ehlers-danlos-syndrome/?from_term=ehlers-danlos+syndrome&from_sort=date&from_size=10&from_pos=6

Hypomorphic zebrafish models mimic the musculoskeletal phenotype of β4GalT7-deficient Ehlers-Danlos syndrome

Spondylodysplastic Ehlers-Danlos syndrome, the B4GALT7 subtype, is caused by biallelic (hypomorphic) mutations in B4GALT7, encoding a pivotal linker enzyme in glycosaminoglycan biosynthesis.

Hypomorphic b4galt7 morphants and crispant zebrafish models, faithfully phenocopy human spEDS-B4GALT7.

B4galt7-deficiency results in reduced amounts of sPG/sGAGs and impairs the biosynthesis of both HS and CS.

Galactosyltransferase I plays a key role in early development and in cartilage, bone and possibly muscle formation.

Our zebrafish models underscore the importance of GAGs during chondrogenesis, chondrocyte intercalation and cartilage morphogenesis.

Our hypomorphic zebrafish models support the hypothesis that the variation in symptom severity between spEDS-B4GALT7 individuals correlates with the amount of residual enzyme activity.

Vascular Ehlers-Danlos Syndrome: Can the Beneficial Effect of Celiprolol Be Extrapolated to Bisoprolol?

https://academic.oup.com/ehjcvp/advance-article/doi/10.1093/ehjcvp/pvz067/5613805

https://pubmed.ncbi.nlm.nih.gov/31693161-vascular-ehlers-danlos-syndrome-can-the-beneficial-effect-of-celiprolol-be-extrapolated-to-bisoprolol/

Vascular Ehlers-Danlos Syndrome: Can the Beneficial Effect of Celiprolol Be Extrapolated to Bisoprolol?

Maria C Gorosabel, Nicolo Dubacher, Janine Meienberg, Gabor Matyas

European Heart Journal – Cardiovascular Pharmacotherapy, pvz067, https://doi.org/10.1093/ehjcvp/pvz067

Published: 06 November 2019

Targetable cellular signaling events mediate vascular pathology in vascular Ehlers-Danlos syndrome

https://www.jci.org/articles/view/130730

https://www.ncbi.nlm.nih.gov/pubmed/31639107?dopt=Abstract

Targetable cellular signaling events mediate vascular pathology in vascular Ehlers-Danlos syndrome.

J Clin Invest. 2019 Oct 22;:

Authors: Bowen CJ, Calderón Giadrosic JF, Burger Z, Rykiel G, Davis EC, Helmers MR, Benke K, Gallo MacFarlane E, Dietz HC

Abstract

Vascular Ehlers-Danlos syndrome (vEDS) is an autosomal-dominant connective tissue disorder caused by heterozygous mutations in the COL3A1 gene, which encodes the pro-alpha 1 chain of collagen III. Loss of structural integrity of the extracellular matrix is believed to drive the signs and symptoms of this condition, including spontaneous arterial dissection and/or rupture, the major cause of mortality. We created two mouse models of vEDS that carry heterozygous mutations in Col3a1 that encode glycine substitutions analogous to those found in patients, and showed that signaling abnormalities in the PLC/IP3/PKC/ERK pathway (phospholipase C/inositol 1,4,5-triphosphate/protein kinase C/extracellular signal-regulated kinase) are major mediators of vascular pathology.Treatment with pharmacologic inhibitors of ERK1/2 or PKC-beta prevented death due to spontaneous aortic rupture. Additionally, we found that pregnancy- and puberty-associated accentuation of vascular risk, also seen in vEDS patients, is rescued by attenuation of oxytocin and androgen signaling, respectively. Taken together, our results provide evidence that targetable signaling abnormalities contribute to the pathogenesis of vEDS, highlighting unanticipated therapeutic opportunities.

PMID: 31639107 [PubMed – as supplied by publisher]

Ehlers-Danlos Syndrome-Related Genes and Serum Strontium, Zinc, and Lithium Levels in Generalized Joint Hypermobility

https://www.tandfonline.com/doi/abs/10.1080/03008207.2019.1675648?journalCode=icts20

https://pubmed.ncbi.nlm.nih.gov/31594391-ehlers-danlos-syndrome-related-genes-and-serum-strontium-zinc-and-lithium-levels-in-generalized-joint-hypermobility-a-case-control-study/

Ehlers-Danlos Syndrome-Related Genes and Serum Strontium, Zinc, and Lithium Levels in Generalized Joint Hypermobility: A Case-Control Study

Abstract

Aim of the study: Generalized joint hypermobility (GJH) is a common feature of almost all Ehlers-Danlos syndrome (EDS) types; however, its genetic basis remains unclear. Therefore, it is crucial to distinguish the genetic basis of GJH from other connective tissue disorders, including the different subtypes of EDS. The aim of this study was to determine the blood EDS-related gene expressions and serum element levels in GJH and reveal their predictive characteristics and correlations with the Beighton score. Materials and Methods: A total of 39 women aged 18-23 years with GJH and 38 age- and sex-matched controls were included in the study. Inductively coupled plasma mass spectrometry was used to analyze the serum levels of zinc (Zn), strontium (Sr), and lithium (Li). The relative expression levels of the EDS-related genes were determined using quantitative real-time polymerase chain reaction (PCR). Results: Our results showed that women with GJH possessed significantly lower Li and higher Zn and Sr levels than the controls. In addition, the gene expressions of TNXB and SLC39A13 were significantly higher, whereas those of COL1A1, COL1A2, COL5A1, FKBP14, and DSE were lower in the GJH group. Pearson correlation analyses revealed a strong negative correlation between the Beighton score and B4GALT7, FKBP14, COL1A1, and Li. However, a significant positive correlation was noted between the Beighton score and SLC39A13, TNXB, Zn, Sr, and B3GALT6. Conclusion: Our findings provide valuable basal levels for conducting gene function analysis of joint hypermobility-related connective tissue disorders.

Neuromuscular activation differences during gait in patients with Ehlers-Danlos syndrome and healthy adults

https://onlinelibrary.wiley.com/doi/abs/10.1002/acr.24067

https://www.ncbi.nlm.nih.gov/pubmed/31498548?dopt=Abstract

Neuromuscular activation differences during gait in patients with Ehlers-Danlos syndrome and healthy adults.

Arthritis Care Res (Hoboken). 2019 Sep 09;:

Authors: Robbins SM, Cossette-Levasseur M, Kikuchi K, Sarjeant J, Shiu YG, Azar C, Hazel EM

Abstract

OBJECTIVE: Ehlers-Danlos syndrome (EDS) is a group of genetic disorders affecting connective tissue and symptoms include joint and ligament laxity. The objectives were to compare muscle activation, joint angles, and spatiotemporal parameters during gait, and isometric strength between participants with EDS (hypermobility and classical subtypes) and healthy adults.

METHODS: Participants with EDS (n=14) and healthy adults (n=14) were recruited for this cross-sectional study. Lower extremity muscle activation, sagittal joint angles, and spatiotemporal parameters during gait were measured using surface electromyography, motion capture, and force plates. Isometric strength of the lower extremity joints was measured with an isokinetic dynamometer. Important characteristics (principal components) were determined from electromyography and angle waveforms using principal component analysis; relationships between principal component scores and groups were examined using multilevel linear models, after accounting for gait speed. Spatiotemporal parameters and strength were compared using independent t-tests and effect sizes (d).

RESULTS: EDS group was associated with delayed vastus lateralis (b=16.69) and medialis activation (b=11.33), higher rectus femoris (b=28.34) and tensor fascia latae (b=-11.06) activation, prolonged gluteus medius activation (b=-32.78), and lower medial gastrocnemius activation (b=-27.18). Joint angles were similar between EDS and healthy groups. EDS group had slower gait speeds, shorter stride lengths, and greater percentage of time in stance (d=-1.05 to 0.96). EDS group had weaker hip and ankle muscles (d=-0.83 to -0.97).

CONCLUSION: Alterations in muscle activation and spatiotemporal parameters during gait in patients with EDS may be a result impaired proprioception and balance, and muscle weakness. Interventions should target these deficits.

PMID: 31498548 [PubMed – as supplied by publisher]

Assessment of the information sources and interest in research collaboration among individuals with Vascular Ehlers-Danlos Syndrome

https://www.annalsofvascularsurgery.com/article/S0890-5096(19)30585-0/fulltext

https://www.ncbi.nlm.nih.gov/pubmed/31449940?dopt=Abstract

Assessment of the information sources and interest in research collaboration among individuals with Vascular Ehlers-Danlos Syndrome.

Ann Vasc Surg. 2019 Aug 23;:

Authors: Shalhub S, Kellogg L, Demasi J, Wallace SE, Fulton DS, Bloom L, Driessnack M, Byers PH, Vascular Ehlers-Danlos Syndrome Collaborative

Abstract

OBJECTIVE: Patient centered research requires active engagement of patients. The Vascular Ehlers-Danlos Syndrome (vEDS) research collaborative was established to ascertain patient-centered vEDS research priorities and to engage affected individuals as research partners. Evaluation of access to information and interest in research among individuals with vEDS was the first step undertaken as part of this work.

METHODS: A 28 question survey was created to evaluate four domains of interest: Diagnostic and clinical care history, vEDS experience, information resources, and willingness to collaborate with researchers. The survey was created in REDCapTM and disseminated between January and April 2018 via the vEDS social media pages, blogs, and advocacy websites. Results were collated and described. A single open-ended question yielded additional narrative data, which were analyzed qualitatively.

RESULTS: Of the 300 responses, 228 (76%) were completed on behalf of oneself. The vEDS diagnosis was confirmed by genetic testing for 85% of respondents. When asked “Did a physician explain vEDS to you and how to manage it?” 25% answered “No”. Most had a primary care provider (PCP) (65%), a cardiologist (56%), and a vascular surgeon (52%). Only 32% had a local vascular surgeon. The most commonly reported frustration was “No cure/treatment available” and the “Emergency rooms do not know what VEDS is” (64.5% and 61.8% respectively). The Internet was the most useful information source (62.3%) followed by a geneticist (18.4%). Most (87.7%) are willing to share their medical records for research studies (87.7%) and wished to be contacted about future studies (83.8%), however, only 65.4% would be willing to upload medical records via a secure confidential web application. The most common reason for interest in research partnership was to advance research for a treatment/cure (83.8%) and helping others learn from their experiences (82.9%). The qualitative analysis provided additional insights into the patient experience living with vEDS.

CONCLUSIONS: Among individuals with vEDS there is substantial frustration with the lack of treatment, lack of knowledge among health care providers, and a high degree of interest in research involvement. The survey highlights an opportunity to discuss the optimal modality for research participation and methodologies for building trust in the research teams. The methodology lessons learned can also be applied to other rare vascular diseases.

PMID: 31449940 [PubMed – as supplied by publisher]

Molecular underpinnings of integrin binding to collagen mimetic peptides containing vascular Ehlers-Danlos syndrome-associated substitutions

http://www.jbc.org/content/early/2019/08/11/jbc.RA119.009685

Molecular underpinnings of integrin binding to collagen mimetic peptides containing vascular Ehlers-Danlos syndrome-associated substitutions

Abstract

Collagens carry out critical extracellular matrix (ECM) functions by interacting with numerous cell receptors and ECM components. Single glycine substitutions in collagen III, which predominates in vascular walls, result in vascular Ehlers-Danlos syndrome (vEDS1), leading to arterial, uterine, and intestinal rupture and an average life expectancy of < 50 years. Collagen interactions with integrin α2β1 are vital for platelet adhesion and activation; however, how these interactions are impacted by vEDS-associated mutations and by specific amino acid substitutions is unclear. Here, we designed collagen mimetic peptides (CMPs) with previously reported Gly→X (X = Ala, Arg, or Val) vEDS substitutions within a high-affinity integrin α2β1 binding motif, GROGER. We used these peptides to investigate, at atomic-level resolution, how these amino acid substitutions affect the collagen III–integrin α2β1 interaction. Using a multi-tiered approach combining biological adhesion assays, CD, NMR, and molecular dynamics (MD) simulations, we found that these substitutions differentially impede human mesenchymal stem cell spreading and integrin α2-inserted (α2I) domain binding to the CMPs and were associated with triple helix destabilization. Although an Ala substitution locally destabilized hydrogen bonding and enhanced mobility, it did not significantly reduce the CMP–integrin interactions. MD simulations suggested that bulkier Gly→X substitutions differentially disrupt the CMP–α2I interaction. The Gly→Arg substitution destabilized CMP–α2I side-chain interactions, and the Gly→Val change broke the essential Mg2+ coordination. The relationship between the loss of functional binding and the type of vEDS substitution provides a foundation for developing potential therapies for managing collagen disorders.

A Novel Frameshift COL3A1 Variant in Vascular Ehlers-Danlos Syndrome: insight into genetic variants and clinical expression of vEDS

https://www.annalsofvascularsurgery.com/article/S0890-5096(19)30553-9/fulltext

https://www.sciencedirect.com/science/article/abs/pii/S0890509619305539

https://www.ncbi.nlm.nih.gov/pubmed/31394236?dopt=Abstract

A Novel Frameshift COL3A1 Variant in Vascular Ehlers-Danlos Syndrome

Ehlers-Danlos syndromes (EDSs) are a group of heritable connective tissue disorders with distinct genetic etiologies. Of the 13 currently recognized types of EDS, the vascular type EDS (vEDS) is generally considered the most severe and is associated with a decreased life expectancy due to spontaneous arterial, intestinal, and or uterine rupture. Diagnosis of vEDS is supported by genetic testing confirming the presence of pathogenic variations in COL3A1, a type III procollagen gene. Management of vEDS is usually conservative with control of hemodynamic stress, frequent cardiovascular imaging, and, if indicated, a thoughtful endovascular intervention or surgical repair. We present a novel frameshift variant in COL3A1 leading to vEDS with multiple vascular involvements. Based on our literature review, this variant has not been reported and may result in a less severe form of vEDS. Our case report provides insight into genetic variants and clinical expression of vEDS.

Patient perspectives on employment participation in the “hypermobile Ehlers-Danlos syndrome”

https://www.tandfonline.com/doi/abs/10.1080/09638288.2019.1636316?journalCode=idre20

https://www.ncbi.nlm.nih.gov/pubmed/31287330?dopt=Abstract

Patient perspectives on employment participation in the “hypermobile Ehlers-Danlos syndrome”.

Disabil Rehabil. 2019 Jul 09;:1-10

Authors: De Baets S, Calders P, Verhoost L, Coussens M, Dewandele I, Malfait F, Vanderstraeten G, Van Hove G, Van de Velde D

Abstract

Background: “Ehlers-Danlos syndrome” (EDS) is a heritable connective disorder influencing multiple aspects of daily life. Most studies have focused on describing the physical symptoms and level of disability, but little knowledge exists about the psychosocial effects of the pathology. Participation in employment is an aspect that strongly influences quality of life of patients with chronic pathologies. This study, therefore, aimed to explore the lived experiences in employment participation of patients diagnosed with “hypermobile EDS”. Methods: An inductive thematic analysis, using semi-structured interviews was used. Nine patients, purposively selected by a continuum sampling strategy, were included. Interviews were audio-recorded and transcribed verbatim. Results: Data analysis resulted in three main themes: (1) elements assisting participation in employment, (2) limitations in employment participation, and (3) unemployment due to the “hypermobile EDS”. On the one hand, the results show that related health complaints can impede employment participation to an important extent. On the other hand, patients also report several aspects of work that can affect their well-being in a positive way. Conclusion: There are specific reasons for a person with “hypermobile EDS” to participate in employment. These reasons are different for each person and may even vary in time. Implications for rehabilitation “Hypermobile EDS” greatly impacts activities and participation in daily life. “Living with limitations” is the central theme in the lives of “Hypermobile EDS” patients. Various aspects influence work participation in people with “Hypermobile EDS”, such as work pressure, tasks, and transport to work. Work has positive effects in the lives of people with “Hypermobile EDS.” Work can create difficulties when the job requirements and tasks do not match the functional abilities of a person with “Hypermobile EDS.”

PMID: 31287330 [PubMed – as supplied by publisher]

Transcriptome Profiling of Primary Skin Fibroblasts Reveal Distinct Molecular Features Between PLOD1- and FKBP14-Kyphoscoliotic Ehlers-Danlos Syndrome

https://www.ncbi.nlm.nih.gov/pubmed/31288483?dopt=Abstract

Transcriptome Profiling of Primary Skin Fibroblasts Reveal Distinct Molecular Features Between PLOD1- and FKBP14-Kyphoscoliotic Ehlers-Danlos Syndrome.

Genes (Basel). 2019 Jul 08;10(7):

Authors: Lim PJ, Lindert U, Opitz L, Hausser I, Rohrbach M, Giunta C

Abstract

Kyphoscoliotic Ehlers-Danlos Syndrome (kEDS) is a rare genetic heterogeneous disease clinically characterized by congenital muscle hypotonia, kyphoscoliosis, and joint hypermobility. kEDS is caused by biallelic pathogenic variants in either PLOD1 or FKBP14. PLOD1 encodes the lysyl hydroxylase 1 enzyme responsible for hydroxylating lysyl residues in the collagen helix, which undergo glycosylation and form crosslinks in the extracellular matrix thus contributing to collagen fibril strength. FKBP14 encodes a peptidyl-prolyl cis-trans isomerase that catalyzes collagen folding and acts as a chaperone for types III, VI, and X collagen. Despite genetic heterogeneity, affected patients with mutations in either PLOD1 or FKBP14 are clinically indistinguishable. We aim to better understand the pathomechanism of kEDS to characterize distinguishing and overlapping molecular features underlying PLOD1-kEDS and FKBP14-kEDS, and to identify novel molecular targets that may expand treatment strategies. Transcriptome profiling by RNA sequencing of patient-derived skin fibroblasts revealed differential expression of genes encoding extracellular matrix components that are unique between PLOD1-kEDS and FKBP14-kEDS. Furthermore, we identified genes involved in inner ear development, vascular remodeling, endoplasmic reticulum (ER) stress, and protein trafficking that were differentially expressed in patient fibroblasts compared to controls. Overall, our study presents the first transcriptomics data in kEDS revealing distinct molecular features between PLOD1-kEDS and FKBP14-kEDS, and serves as a tool to better understand the disease.

PMID: 31288483 [PubMed]

Ehlers-Danlos syndrome and other heritable connective tissue disorders that impact pregnancies can be detected using next-generation DNA sequencing

https://link.springer.com/article/10.1007%2Fs00404-019-05226-5

https://www.ncbi.nlm.nih.gov/pubmed/31250196?dopt=Abstract

Related Articles

Ehlers-Danlos syndrome and other heritable connective tissue disorders that impact pregnancies can be detected using next-generation DNA sequencing.

Arch Gynecol Obstet. 2019 Jun 27;:

Authors: VanderJagt K, Butler MG

Abstract

Ehlers-Danlos syndromes (EDS) are a genetically heterogeneous group of inherited connective tissue disorders classified into six major types with a variable collection of findings and different inheritance patterns. Although complications occur in about one-half of pregnancies in women with EDS, the majority can have a good outcome if managed appropriately. Classic EDS is characterized by joint hypermobility, loose skin with poor healing and easy bruising, musculoskeletal problems with chronic pain and at risk for pre-term delivery. In addition, the vascular form of EDS can have cardiac anomalies, aneurysms, gastrointestinal perforation and uterine rupture during pregnancy. Due to overlapping features among the connective tissue disorders, it is difficult to categorize the disorder into specific types without detailed genetic testing which is now available through advanced genomic technology using next-generation DNA sequencing, searching genomic databases and bioinformatics approach. Therefore, obstetrical complications are variable but relate to specific connective tissue disorders requiring an exact diagnosis. There are several dozen genes causing connective tissue disorders that are currently available for testing using next-generation sequencing and bioinformatics to provide pertinent care, treatment and surveillance of the affected pregnant woman but also for her at-risk fetus related to the specific heritable condition.

PMID: 31250196 [PubMed – as supplied by publisher]

An acquired or heritable connective tissue disorder? A review of hypermobile Ehlers Danlos Syndrome

https://www.sciencedirect.com/science/article/pii/S1769721218309364?via%3Dihub

https://www.ncbi.nlm.nih.gov/pubmed/31102747?dopt=Abstract

Related Articles

An acquired or heritable connective tissue disorder? A review of hypermobile Ehlers Danlos Syndrome.

Eur J Med Genet. 2019 Jul;62(7):103672

Authors: Martin A

Abstract

Hypermobile Ehlers Danlos Syndrome (hEDS) is a multifaceted disorder that is difficult to diagnose and manage primarily due to the unknown causes. Research on hEDS continues to evolve but tangible progress will be realized when the growing body of evidence compliments clinical practice. This critical review of the literature aims to stimulate lateral thinking about the pathogenesis, diagnosis and management of hEDS. The current international classification of Ehlers Danlos Syndrome introduced stricter diagnostic criteria for hEDS, which bore a blanket category (hypermobility spectrum disorders) for conditions presenting with symptomatic joint hypermobility, but do not match the hEDS diagnostic criteria. One would argue hEDS is another all-encompassing classification for heritable connective tissue disorders and or acquired musculoskeletal conditions without a definitive molecular basis. As scientific research progresses to accommodate validated and or annulled hypotheses, the plethora of unknowns in hEDS continue to challenge healthcare outcomes and care experiences.

PMID: 31102747 [PubMed – indexed for MEDLINE]

Genetic basis of hereditary thoracic aortic aneurysms and dissections, including vascular Ehlers-Danlos syndrome

https://www.journal-of-cardiology.com/article/S0914-5087(19)30086-3/fulltext

https://www.ncbi.nlm.nih.gov/pubmed/31000321?dopt=Abstract

Related Articles

Genetic basis of hereditary thoracic aortic aneurysms and dissections.

J Cardiol. 2019 Apr 15;:

Authors: Takeda N, Komuro I

Abstract

Recent advances in DNA sequencing technology have identified several causative genes for hereditary thoracic aortic aneurysms and dissections (TAADs), including Marfan syndrome (MFS), Loeys-Dietz syndrome, vascular Ehlers-Danlos syndrome, and familial non-syndromic TAADs. Syndromic TAADs are typically caused by pathogenic variants in the transforming growth factor-β signal and extracellular matrix-related genes (e.g. FBN1, TGFBR1, TGFBR2, SMAD3, TGFB2, and COL3A1). On the other hand, approximately 20% of the non-syndromic hereditary TAADs result from altered components of the contractile apparatus of vascular smooth muscle cells, which are encoded by ACTA2, MYH11, MYLK, and PRKG1 genes; however, the remaining 80% cannot be explained by previously reported candidate genes. Moreover, the relationship between the genotype and phenotype of TAADs has extensively been reported to investigate better methods for risk stratification and further personalized treatment strategies. With regard to MFS-causing FBN1, recent reports have shown significantly increased risk of aortic events in patients carrying a truncating variant or a variant exhibiting a haploinsufficient-type effect, typically comprising nonsense or small insertions/deletions resulting in out-of-frame effects, compared to those carrying a variant with dominant negative-type effect, typically comprising missense variants. Therefore, cardiologists are required to have sufficient knowledge regarding the genetics of hereditary TAADs for providing the best clinical management, with an appropriate genetic counseling. In the current review, we present current advances in the genetics of hereditary TAADs and discuss the benefits and limitations with respect to the use of this genetic understanding in clinical settings.

PMID: 31000321 [PubMed – as supplied by publisher]

Response to growth hormone therapy in patients with B4GALT7-associated spondylodysplastic Ehlers-Danlos syndrome

https://www.sciencedirect.com/science/article/pii/S8756328219301139?via%3Dihub

https://www.ncbi.nlm.nih.gov/pubmed/30914273?dopt=Abstract

Related Articles

Phenotype and response to growth hormone therapy in siblings with B4GALT7 deficiency.

Bone. 2019 Mar 23;:

Authors: Sandler-Wilson C, Wambach JA, Marshall BA, Wegner DJ, McAlister W, Cole FS, Shinawi M

Abstract

B4GALT7 encodes beta-1,4-galactosyltransferase which links glycosaminoglycans to proteoglycans in connective tissues. Rare, biallelic variants in B4GALT7 have been associated with spondylodysplastic Ehlers-Danlos and Larsen of Reunion Island syndromes. Thirty patients with B4GALT7-related disorders have been reported to date with phenotypic variability. Using whole exome sequencing, we identified male and female siblings with biallelic, pathogenic B4GALT7 variants and phenotypic features of spondylodysplastic Ehlers-Danlos syndrome as well as previously unreported skeletal characteristics. We also provide detailed radiological characterization and describe the siblings’ responses to growth hormone treatment. Our report extends the phenotypic spectrum of B4GALT7-associated spondylodysplastic Ehlers-Danlos syndrome and reports results of growth hormone treatment for patients with this rare disorder.

PMID: 30914273 [PubMed – as supplied by publisher]

Inspiratory muscle strength training (IMT) improves lung function in patients with the hypermobile Ehlers-Danlos syndrome

https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.a.61016

https://www.ncbi.nlm.nih.gov/pubmed/30569502?dopt=Abstract

Related Articles

Inspiratory muscle strength training improves lung function in patients with the hypermobile Ehlers-Danlos syndrome: A randomized controlled trial.

Am J Med Genet A. 2019 03;179(3):356-364

Authors: Reychler G, Liistro G, Piérard GE, Hermanns-Lê T, Manicourt D

Abstract

As exertional inspiratory dyspnea is a common disabling complaint in hypermobile Ehlers-Danlos syndrome (hEDS) often also known as joint hypermobility syndrome (JHS), we investigated inspiratory muscle (IM) strength in patients with hEDS, and we assessed the effects of IM training (IMT) on IM strength, lung function, and exercise capacity. A prospective evaluation of IM strength followed by a randomized controlled trial of IMT was performed in women with hEDS. Sniff nasal inspiratory pressure (SNIP) was used to routinely measure IM strength and IMT was carried out using a pressure threshold device. IM strength (main outcome), cardiopulmonary function, exercise capacity, and emotional distress of both the treated and control groups were evaluated at the start and at the end of the 6-week training period. IM strength was reduced (<80% of predicted) in 77% of patients (80/104). Lung function was normal, although 24% of patients had a higher forced expiratory vital capacity (FVC) than normal and 12% of patients had a higher total lung capacity (TLC) than normal. Both the IMT and control groups (n = 20) had similar baseline characteristics. Significant changes were noted only in the IMT group after IMT. At the end of the program, IMT improved SNIP (20%) (before: 41 ± 17 cm H2 O [28, 53] vs. after: 49 ± 18 cm H2 O [34;65]), six-minute walking distance (6MWD) (60 m) (455 ± 107 m [379,532] vs. 515 ± 127 m [408, 621]), and forced expiratory volume in one second (FEV1) (285 mL) (94 ± 14% pred [84,104] vs. 103 ± 11% pred [94, 112]). IM strength is significantly reduced in patients with hEDS. IMT improved IM strength, lung function, and exercise capacity. Our findings suggest that IMT should be added to usual care. PMID: 30569502 [PubMed - indexed for MEDLINE]

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