Laryngological presentations and patient-reported outcome measures in Ehlers-Danlos syndrome

OBJECTIVE: This study aimed to characterise the laryngological presentations of Ehlers–Danlos syndrome and conduct a preliminary exploration of patient-reported outcome measures. METHODS: This paper describes a retrospective case series of patients with Ehlers–Danlos syndrome seen by the senior author between 2005 and 2019. A literature review was conducted to summarise the existing findings. RESULTS: Twenty-one patients met the inclusion criteria. All reported symptoms were grouped; this showed that swallowing, voice and hyolaryngeal skeletal complex problems were commonest. Patient-reported outcome measures were available for eight patients, which showed large variations in: the Reflux Severity Index (median = 25.5; range = 0–33), Eating Assessment Tool score (median = 21.5; range = 0–35) and Voice Handicap Index (median = 21.5; range = 0–104). Twelve studies met our literature review inclusion criteria, involving at least 91 patients with laryngological presentations of Ehlers–Danlos syndrome. CONCLUSION: Ehlers–Danlos syndrome patients experience musculoskeletal issues, which in the throat manifest as hyolaryngeal skeletal complex problems. Future studies with larger patient numbers are required to validate laryngological patient-reported outcome measure tools in Ehlers–Danlos syndrome

Adenoviral Gene Transfer Restores Lysyl Hydroxylase Activity in Type VI Ehlers-Danlos Syndrome

Type VI Ehlers-Danlos syndrome is a disease characterized by disturbed lysine hydroxylation of collagen. The disease is caused by mutations in lysyl hydroxylase 1 gene and it affects several organs including the cardiovascular system, the joint and musculoskeletal system, and the skin. The skin of type VI Ehlers-Danlos syndrome patients is hyperelastic, scars easily, and heals slowly and poorly. We hypothesized that providing functional lysyl hydroxylase 1 gene to the fibroblasts in and around wounds in these patients would improve healing. In this study we tested the feasibility of transfer of the lysyl hydroxylase 1 gene into fibroblasts derived from rats and a type VI Ehlers-Danlos syndrome patient (in vitro) and into rat skin (in vivo). We first cloned human lysyl hydroxylase 1 cDNA into a recombinant adenoviral vector (Ad5RSV-LH). Transfection of human type VI Ehlers-Danlos syndrome fibroblasts (about 20% of normal lysyl hydroxylase 1 activity) with the vector increased lysyl hydroxylase 1 activity in these cells to near or greater levels than that of wild type, unaffected fibroblasts. The adenoviral vector successfully transfected rat fibroblasts producing both β-galactosidase and lysyl hydroxylase 1 gene activity. We next expanded our studies to a rodent model. Intradermal injections of the vector to the abdominal skin of rats produced lysyl hydroxylase 1 mRNA and elevated lysyl hydroxylase 1 activity, in vivo. These data suggest the feasibility of gene replacement therapy to modify skin wound healing in type VI Ehlers-Danlos syndrome patients

A Cellular and Genetic Approach to Ehlers-Danlos Syndrome

This paper serves as an in-depth exploration of a rare genetic disorder, Ehlers-Danlos Syndrome, discussing its genetic basis and pathology, as well as offers a unique perspective from those who are afflicted by it. Ehlers-Danlos Syndrome (EDS) is a connective tissue disorder that ultimately stems from a rare genetic mutation and disruption of the extracellular matrix. Thirteen different variations of this possibly life-threatening syndrome have been established. The types of EDS have different genes that are mutated to specifically result in the variant. The focus of this proposal is the vascular variation, otherwise referred to as vEDS. Vascular Ehlers-Danlos Syndrome can remain hidden until there is a rupture in a major artery. There are two known genetic mutations of the COL3A1 gene that result in vEDS, an amino acid substitution and deletion of multiple exons. These mutations lead to a defective production or lack of production of type III collagen from the alpha-1 chain. This mutated collagen manufacturing leads to increased tissue fragility, particularly in blood vessels. Abdominal Vascular Compression Syndromes (AVCS) all involve some sort of underlying susceptibility to compression of major vessels, but it has yet to be discovered. The umbrella-group AVCS is compiled of Median Arcuate Ligament Syndrome, May-Thurner Syndrome, Nutcracker syndrome, and more. As a new and upcoming research subject, AVCS demonstrates a correlation between each of the syndromes and now even connections with Ehlers-Danlos Syndrome. In order to better understand the contemporary relationship between EDS and AVCS, a deeper analysis of the genetics of Ehlers-Danlos Syndrome, as well as its effects, would be beneficial to patients who suffer from this syndrome and those that fall into the AVCS category

Exercise Beliefs and Behaviours of Individuals with Joint Hypermobility Syndrome/ Ehlers Danlos Syndrome-Hypermobility Type

This is an Accepted Manuscript of an article published by Taylor & Francis Group in Disability & Rehabilitation on 10 November 2017, available online at: https://doi.org/10.1080/09638288.2017.1398278. © 2017 Informa UK Limited, trading as Taylor & Francis GroupPurpose: To explore exercise beliefs and behaviours of individuals with Joint Hypermobility syndrome/Ehlers–Danlos syndrome – hypermobility type and to explore patient experiences of physiotherapy.Methods: A cross sectional questionnaire survey design was used to collect quantitative and qualitative data from adult members of the Hypermobility Syndromes Association and Ehlers–Danlos Syndrome Support UK. Descriptive and inferential statistics were used to analyse the data. Qualitative data was analysed thematically.Results: 946 questionnaires were returned and analysed. Participants who received exercise advice from a physiotherapist were 1.75 more likely to report high volumes of weekly exercise (odds ratio [OR] = 1.75, 95% confidence interval [CI] = 1.30–2.36, p < 0.001) than those with no advice. Participants who believed that exercise is important for long-term management were 2.76 times more likely to report a high volume of weekly exercise compared to the participants who did not hold this belief (OR = 2.76, 95% CI = 1.38–5.50, p = 0.004). Three themes emerged regarding experience of physiotherapy; physiotherapist as a partner, communication – knowledge, experience and safety.Conclusion: Pain, fatigue and fear are common barriers to exercise. Advice from a physiotherapist and beliefs about the benefits of exercise influenced the reported exercise behaviours of individuals with Ehlers–Danlos syndrome – hypermobility type in this survey.Peer reviewe

Spontaneous Coronary Artery Dissection as Presenting Feature of Vascular Ehlers-Danlos Syndrome

A spontaneous coronary artery dissection as the sole presenting feature of vascular Ehlers-Danlos syndrome is an uncommon finding. We present a 33-year-old woman with sudden onset chest pain caused by a spontaneous coronary artery dissection. Genetic testing revealed vascular Ehlers-Danlos syndrome as the underlying cause. Specifically, we show the value of genetic testing, which in some patients may be the only way of establishing a diagnosis

Vascular ehlers-danlos syndrome: a rare disorder presenting with focal convulsions

Vascular Ehlers-Danlos Syndrome (VEDS), previously called Ehlers-Danlos syndrome type-IV, is a heterogeneous group of heritable connective tissue disorders characterized by thin, translucent skin, easy bruising, arterial, intestinal, and/or uterine fragility. There is large vessel involvement that leads to arterial rupture often preceded by aneurysm, arteriovenous fistulae, or dissection. Noninvasive imaging studies such as CT angiography and MR angiography are preferred as diagnostic studies for this condition. We are reporting a 4 years old girl who was presented with right sided unilateral convulsions and hypertension. CT angiogram showed stenosis with post-stenotic dilatation of coeliac and superior mesenteric arteries. There were extensive calcified plaques with atherosclerotic changes in the segment of right common iliac artery with aneurysmal dilatation of celiac, superior mesenteric and common iliac artery. Radiological findings were consistent with vascular Ehlers-Danlos syndrome. She was successfully managed with anti-hypertensive and anticonvulsants

Rupture of abdominal aortic aneurysm after spine surgery in the patient with Ehlers-Danlos syndrome -A case report-

Ehlers-Danlos syndrome (EDS) is a rare inherited disorder of the connective tissue that is characterized by hyperextensible skin, hypermobile joints and abnormalities of the cardiovascular system. A 15-year-old girl with Ehlers-Danlos syndrome underwent thoracolumbar surgery for deformity correction. After surgery, an abdominal aortic rupture occurred, and she complained of abdominal distension had an abdominal circumference of 80 cm. Abdominal computed tomography revealed a pseudoaneurysm and a large hematoma at the retroperitoneum. She died of a massive hemorrhage during subsequent abdominal aortic surgery

Az Ehlers–Danlos-szindrómák korszerű osztályozása és multidiszciplináris tünettana = Up-to-date classification and multidisciplinary symptoms of Ehlers–Danlos syndromes

Absztrakt: A szerzők a ritka, örökletes kötőszöveti betegségek közé tartozó Ehlers–Danlos-szindrómacsoportra vonatkozó korszerű, nemzetközi osztályozáson alapuló klinikai ismereteket foglalják össze. Az Ehlers–Danlos-szindrómacsoport vezető tünete az ízületi hipermobilitás, a bőrhiperextenzibilitás és az általános szöveti fragilitás. Az Ehlers–Danlos-szindróma klinikailag és genetikailag nagyfokú heterogenitást mutató multidiszciplináris jelentőségű betegségcsoport. A szindróma egyes altípusai elsősorban az életminőséget rontják, de bizonyos formái súlyos, fatális kimenetelű vascularis és intestinalis komplikációkhoz vezethetnek. A nemzetközi gyakorlatban nagy esetszámban megvalósult genotípus-fenotípus korrelációs vizsgálatok szolgáltatta adatok alapján a szindróma klinikai alcsoportjainak új osztályozását vezették be. Az Ehlers–Danlos-szindrómák 2017-ben közreadott korszerű, nemzetközi nozológiája 13 klinikai alcsoportot különít el, megadva azok genetikai hátterét, öröklődésmenetét, és definiálja az egyes altípusok major és minor diagnosztikus kritériumrendszerét. Az Ehlers–Danlos-szindrómák összetett, multidiszciplináris tüneteit a differenciáldiagnosztikai gondolkodást segítő összefoglaló táblázatba gyűjtöttük össze. A mindennapi orvosi gyakorlatban az Ehlers–Danlos-szindrómák által érintett betegek azonosítása a klinikai gondozás feladatainak meghatározását és ezáltal a súlyos szövődmények prevencióját szolgálja. Orv Hetil. 2019; 160(16): 603–612. | Abstract: In this review article, the authors summarize the clinical aspects of the novel classification of Ehlers–Danlos syndrome, which is a group of rare, hereditary connective tissue disorders. The leading symptom of the Ehlers–Danlos syndrome group is joint hypermobility, skin hyperextensibility and generalized tissue fragility. Ehlers–Danlos syndrome displays a high clinical and genetic heterogeneity and harbors many multidisciplinary properties. Certain subtypes only affect the quality of life, while other forms may lead to severe, even fatal vascular or intestinal complications. Last year, based on the data of various international genotype-phenotype correlation studies of large populations, a new classification of the syndrome’s clinical subtypes was introduced. The novel international nosology of Ehlers–Danlos syndromes published in 2017 delineates 13 clinical subtypes, describes their genetic background and defines major and minor diagnostic criteria for each subtype. We gathered the complex, multidisciplinary symptoms of Ehlers–Danlos syndromes in a table to assist the diagnosis from a differential diagnostic point of view. In the clinical practice, the proper diagnosis of patients affected by the Ehlers–Danlos syndrome group is essential to give optimal clinical care and to prevent the development of severe complications. Orv Hetil. 2019; 160(16): 603–612

Pain Control Methods in Use by Patients With Ehlers-Danlos Syndrome and Pain Control Effectiveness

The purpose of this study is to assess the pain control methods in use by patients who have Ehlers-Danlos Syndrome, a group of connective tissue disorders. This descriptive study involved 1179 adults diagnosed with Ehlers-Danlos Syndrome who completed an anonymous on-line survey. The survey consisted of demographics information, the PROMIS Pain-Behavior, Pain-Interference, and Satisfaction with Social Roles and Activities scales, as well as a modified version of the Pain Management Strategies Survey (PMSS). Among the treatment modalities participants reported in this study, the most helpful for acute pain control were opioids, surgical interventions, splints and braces, heat therapy, nerve blocks, and physical therapy. Chronic pain was treated most effectively with opioids, heat therapy, splints or braces, and surgical interventions. Knowledge of pain management practices and perceptions of benefit is important for understanding how to support individuals with Ehlers-Danlos Syndrome. Increasing knowledge in this area could help clinicians better advise individuals who experience persistent pain as to pain management strategies most likely to be considered beneficial by the patient

Celiprolol: A Unique Selective Adrenoceptor Modulator

Celiprolol is a β-blocker with a unique pharmacologic profile: it is a β1-andrenoceptor antagonist with partial β2 agonist activity. Given this combination of effects, celiprolol may be better described as a selective adrenoreceptor modulator. It has antihypertensive and antianginal properties and is indicated for those uses in various countries around the world. In the United States, however, the proposed indication for this drug will be for the treatment of vascular type Ehlers-Danlos syndrome, a rare connective tissue disorder characterized by fragile arterial structure and an increased risk of life-threatening vascular complications. By reducing heart rate and pulsatile pressure, celiprolol may reduce the mechanical stress on collagen fibers within the arterial wall and be of benefit in patients with vascular type Ehlers-Danlos syndrome. The largest investigation of celiprolol in vascular Ehlers-Danlos syndrome was prematurely terminated due to significant benefit with celiprolol in reducing arterial events in patients with this condition. Celiprolol, therefore, represents a β-blocker that is unique from others in its class in both its pharmacology and clinical applications