Vascular Type Of Ehlers-Danlos Syndrome Research Articles

Clinical features and morphology of collagen fibrils in patients with vascular Ehlers-Danlos based on electron microscopy.

Background: Vascular-type Ehlers-Danlos syndrome (vEDS) is caused by collagen III deficit resulting from heterogeneous mutations in COL3A1, which occasionally causes sudden death due to arterial/visceral rupture. However, it is difficult to conduct basic research on the pathophysiology of vEDS. Moreover, the number of patients with vEDS is small, limiting the number of available samples. Furthermore, the symptoms of vEDS may vary among family members, even if they share the same mutation. Accordingly, many aspects of the pathology of vEDS remain unknown. Therefore, we investigated the structural abnormalities in collagen fibrils and endoplasmic reticulum (ER) stress in skin samples using electron microscopy as well as their relationship with clinical symptoms in 30 patients with vEDS (vEDS group) and 48 patients without vEDS (disease-negative control group). Methods: Differences between the two groups were evaluated in terms of the sizes of collagen fibrils using coefficient of variation (COV). Results: COV was found to be significantly higher in the vEDS group than in the disease-negative control group, indicating irregularity in the size of collagen fibrils. However, in the vEDS group, some patients had low COV and seldom experienced serious complications and ER stress. Conclusion: ER stress might affect collagen fibril-composing proteins. Moreover, as this stress varies among people based on environmental factors and aging, it may be the underlying cause of varying vEDS symptoms.

Direct Inspection of Primary Aortic Cell Transcriptomes Identifies Candidate Causative Variants in Patients with Thoracic Aortic Aneurysm

Background: Thoracic aortic aneurysm (TAA) is an aortopathy that predisposes to life-threatening aortic dissection. Autosomal dominant disorders associated with TAA include Marfan syndrome (FBN1), Loeys-Dietz syndrome (TGFBR1/2, SMAD3, TGFB2), and vascular type Ehlers-Danlos syndrome (COL3A1). Our objective was to identify single nucleotide variants (SNVs) in these six genes within the transcriptomes of primary aortic cells acquired from patients with aortopathy.Methods: Primary aortic cell lines were cultured directly from the medial layer of surgically explanted aortic tissues in 63 unrelated aortopathy patients. RNA samples were extracted from aortic cells for mRNA sequencing. RNA reads aligning to the 6 selected TAA genes were directly inspected using Integrative Genomics Viewer (Broad Institute), and the identified SNVs were filtered for downstream analysis.Results: Study patients were predominantly male and of European ancestry with a mean age of 52±18 years. Thirty-three (52%) patients had a bicuspid aortic valve, and 10 (16%) had family history of TAA or dissection. A total of 3740 SNVs were identified in patient transcriptomes, and these occurred at 905 distinct genomic coordinates. There were 115 SNVs that were unique within the cohort, not located within a 3’-untranslated region, and had ≥20 aligned reads at the SNV’s position. Using the application Franklin (Genoox) to estimate clinical interpretation, 8 unique SNVs were classified as pathogenic (P) or likely pathogenic (LP). Five of these P/LP SNVs were associated with reduced allelic expression, and gene expression level was below the 20th percentile of study samples for 6 P/LP SNVs. Eighty-six unique SNVs were classified as variants of uncertain significance (VUSs). A total of 39 patients (62%) had at least one SNV classified as P/LP/VUS.
 Conclusion: Transcriptomic analysis of primary aortic cells identified candidate causative SNVs and their relative allelic expression. Further analyses will investigate additional TAA-associated genes and integrate transcriptional abnormalities with genetic variants.

Annular elastolytic giant cell granuloma in a patient with Ehlers–Danlos syndrome

The article presents a clinical case of annular elastolytic giant cell granuloma (AEGCG) in a young patient with a vascular type of EhlersDanlos syndrome. The first clinical manifestations of AEGCG appeared on the skin in the right subclavian area about two years ago. Subsequently, new rashes appeared on the skin of the upper and lower extremities up to four new foci per year. The patient underwent ambulatory therapy as a solution of calcium gluconate 10% 5.0 ml No 10 i/v in every other day; a solution of chloropyramine hydrochloride 1.0 ml No 10 i/m every other day; betamethasone + salicylic acid ointment applied to the affected areas of the skin 2 times a day for 2 weeks. The treatment was ineffective, the rashes did not regress. External therapy with tacrolimus was carried out next, 0.1% ointment 2 times a day in the form of applications for 24 weeks but also without effect. The patient by herself started to take a dietary supplement containing 400 mg of collagen in 1 tablet; 3 types of amino acids 20 mg; vitamins B2 1.1 mg; B6 1.5 mg; calcium pantothenate 5 mg 2 tablets a day during meals. A month after the start of the application, she noticed a slight paling of the rashes. At the moment, the patient is under follow up.

Refractory recurrent hemopneumothorax associated with vascular-type Ehlers-Danlos syndrome

Refractory recurrent hemopneumothorax associated with vascular-type Ehlers-Danlos syndrome

Clinical manifestation of coronary pulmonary arterial fistula diagnosed by cardiac computed tomography

Abstract Funding Acknowledgements Type of funding sources: None. Background Coronary pulmonary arterial fistula (CPAF) may cause enlargement of an aneurysm, which may rupture or compress other organs, or occurrence of steal phenomenon of coronary arterial (CA) blood flow. We hypothesize that there are various clinical characteristics of CPAF including patient age at diagnosis, method of diagnosis, observed symptoms, complications, and surgical interventions Methods From a total of >17,000 patients undergoing CT from 2000-2019 in our institute, 11 patients diagnosed as having CPAF were analyzed retrospectively. One was treated surgically prior to analysis, and the remaining 10 (3 males; 56 ± 12 years) were followed for a mean of 52 ± 64 months. Results 5 were diagnosed as having CPAF through cardiac CT and 2 were diagnosed by invasive coronary angiograms. One was diagnosed by TTE and another patient was diagnosed by TTE and cardiac CT to differentiate from a mediastinal tumor. 4 had dyspnea, 2 had chest pain, and 1 had palpitation. 5 showed other cardiovascular disease (1 with left ventricular non-compaction, and persistent left superior vena cava; 1 with vascular type Ehlers-Danlos syndrome; 1 with hypertrophic cardiomyopathy; 1 with aortic valve regurgitation (AR); and 1 with vasospastic angina pectoris). The occurrence of steal phenomenon of CA blood flow was diagnosed in 4. CA aneurysm was observed in 5. 2 had abnormal flow from descending aorta to pulmonary arteries through CA. Pulmonary arterial systolic pressure >30 mmHg was observed in 2. During the observed periods, 4 underwent surgical procedure to eliminate CA aneurysm (N = 2), or for significant steal phenomenon of CA blood flow (N = 1). A patient with AR underwent CPAF elimination simultaneously with aortic valve replacement. The mean periods between initial diagnoses and surgical intervention was 27 ± 36 months. The remaining 6 were followed without surgical intervention for a mean of 69 ± 76 months without any cardiac events. Conclusion CPAF was diagnosed at a mean age of 56 years and half were diagnosed incidentally by cardiac CT. Five of the 11 patients (45%) underwent a surgical procedure. Patients with CPAF showed various symptoms due to complicating diseases, anatomical configurations, and outcomes. Abstract Figure. Typical CT images of CPAF

Chronic Low Back Pain Occurring in Association With Hypermobility Spectrum Disorder and Ehlers-Danlos Syndrome

This review paper outlines recent advances in diagnostic criteria for hypermobility spectrum disorder (HSD) and its association with Ehlers-Danlos syndrome (EDS), as well as current literature on the association between joint hypermobility syndrome and lumbar back pain. We outline the optimal multidisciplinary management of lumbar back pain in the context of joint hypermobility syndrome, as well as the indications and possible side effects of surgical management of patients with these conditions.Several studies have suggested a link between chronic low back pain and hypermobility. HSD has been described as an excessive range of motion in a joint, when accounting for patient demographics. The nomenclature surrounding symptomatic joint hypermobility has varied historically, and various groups, including most notably the international EDS consortium, have introduced new classification schemes to acknowledge the systemic effects of joint hypermobility, which were previously poorly understood. Narrative literature review. Not applicable. Lower back pain experienced in patients on the HSD-EDS spectrum is multifactorial in origin and should not be considered solely in anatomical terms. Caution has been advised in the surgical management of patients on the HSD-hEDS spectrum, particularly where the subtype is unclear. The vascular type of EDS has a particular propensity for severe bleeding complications. Rates of perioperative complications after lumbar spinal surgery in the hypermobile EDS population have been reported to be up to 50%. When hypermobility and chronic lumbar back pain coexist, we advocate management in a multidisciplinary setting involving physiotherapists, pain physicians, surgeons, and psychologists.

Pediatric Innominate Artery Pseudoaneurysm Rupture in Vascular Ehlers-Danlos Syndrome: A Case Report.

IntroductionEhlers-Danlos syndrome is a well classified connective tissue disorder recognized by its features of hyperextensibility of joints and hyperelasticity of the skin. However, the rare vascular type (Ehlers-Danlos type IV) is more difficult to identify in the absence, rarity, or subtlety of the classical physical features. Patients presenting to the emergency department (ED) with acute complications of vascular Ehlers-Danlos syndrome may be critically ill, requiring accurate diagnosis and tailored management.Case ReportThis report details a case of spontaneous innominate artery pseudoaneurysm rupture in a pediatric patient with previously undiagnosed Ehlers-Danlos syndrome. Initial ED evaluation was followed by urgent operative intervention and subsequent genetic testing to confirm final diagnosis.ConclusionDue to its high morbidity and mortality, vascular type Ehlers-Danlos syndrome should be considered in the differential for otherwise unexplained spontaneous vascular injury.

Endoplasmic reticulum stress and collagenous formation anomalies in vascular-type Ehlers-Danlos syndrome via electron microscopy.

Vascular-type Ehlers-Danlos syndrome (vEDS) is an autosomal-dominant inherited disorder caused by a deficit in collagen III. It results from heterogeneous mutations in the α1 collagen III gene (COL3A1) and is associated with life-threatening complications, even in younger patients. However, the details of the pathogenesis underlying the COL3A1 mutation causing vEDS remain unclear. Here, we focus on anomalies in collagen fiber size and the endoplasmic reticulum (ER) stress response in patients with vEDS using electron microscopy (EM). We discovered that although the infants did not have vEDS, collagenous formations were similar to their samples in vEDS. Moreover, we examined the expression of activating transcription factor 6 (ATF6) as an ER stress marker and cartilage oligomeric matrix protein (COMP) as a binding partner protein for collagen fibrils in the dermis and COL3A1. The expression levels of ATF6 in the vEDS group were significantly higher than in infants and controls; COMP and COL3A1 levels were significantly lower. The fragile collagen fibrils in vEDS might form as a result of ER stress and that small, newly formed collagen fibrils may appear. This research revealed a novel prospect regarding an issue that has been unclear for a long time, which is the reason for the abnormal sizes of collagenous fibrils in vEDS.

Vascular Type of Ehlers–Danlos Syndrome – a Rare Monogenic Connective Tissue Disease

The Ehlers-Danlos syndrome is a rare (orphan) disease characterized by the connective tissue dysplasia, fragility of the blood vessels and tissues, and variable clinical pattern. The vascular type of Ehlers-Danlos syndrome, which belongs to Group A according to the classification of 2017, is caused by the mutations in gene of alpha-1 chain of type III collagen COL3A1. The disease is characterized by the high mortality rate of the patients due to the spontaneous ruptures of the vascular walls and hollow viscera. The International Consortium (2017) developed the criteria for the clinical diagnosis of the vascular type of Ehlers – Danlos syndrome. The clinical case of the 16-year-old male patient with vascular type of Ehlers – Danlos syndrome is presented. The molecular genetic testing revealed in the child the previously described pathogenic mutation of splice site p.Gly798_Pro815del of COL3A1 gene associated with the severe course of the disease. In spite of the set of therapy measures aimed at the vascular reinforcement, stimulation and normalization of energy and mineral metabolism, the death occurred in 10 months due to the rupture of the aorta and renal artery. The Conclusion of the forensic medical examination is presented. The results of the care presented indicate that in order to avoid the omission of patients, it is advisable to revise the minimum set of signs required for the clinical diagnosis.

腎動脈破裂で発症し，次世代シークエンサーを用いて診断に至った血管型エーラス・ダンロス症候群の1例

腎動脈破裂で発症し，次世代シークエンサーを用いて診断に至った血管型エーラス・ダンロス症候群の1例

Multivessel endovascular therapy for undiagnosed vascular type Ehlers-Danlos syndrome. Successful percutaneous transcatheter coil embolization of hepatic artery pseudoaneurysm with stenting of right renal and iliac arteries in emergency setting

Among Ehlers-Danlos syndromes, the vascular type is the most severe because of its vascular complications. Transcatheter embolization of medium-sized arteries has become the first-line therapy for life-threatening hemorrhage. Ongoing multiple lesions causing hemorrhagic or ischemic complications in the acute phase can challenge patient management. Multivessel endovascular treatment has never been reported. In this study, we report successful single-session treatment by coiling of a ruptured pseudoaneurysm of the hepatic artery with stenting of dissected right renal and iliac arteries in a 46-year-old female. Percutaneous transfemoral approach was gained and sealed with a plug-based closure device. Genetic disease was subsequently confirmed by molecular analysis.

A four-generation pedigree of vascular-type Ehlers–Danlos syndrome with spontaneous aortic dissections and multiple aneurysms: A case report and literature review

Ehlers-Danlos syndrome (EDS) is a rare, heritable connective tissue disorder disease . Among the subtypes of EDS, vascular type EDS (VEDS), is the most catastrophic one which can lead to aortic aneurysm, aortic dissection and even aortic rupture. We report a four-generation pedigree of VEDS. We give the propositus and her sister a DNA Test and made a literature review about the treatment of VEDS. The diagnosis turned out to be VEDS, which is caused by mutations in COL3A1(c.2221G>A, p.G741S), The patient received conservative treatment and her family got the medical instructions. Although EDS is rarely seen, it is necessary to be aware of this disease to make the right diagnosis and chose the appropriate treatment strategy, Doctors' unfamiliarity with this disease may compromise care.

Gastrointestinal: Huge submucosal hematoma of the stomach arising in a patient with vascular type Ehlers-Danlos syndrome.

Gastrointestinal: Huge submucosal hematoma of the stomach arising in a patient with vascular type Ehlers-Danlos syndrome.

Temporary Abdominal Closure after Surgical Repair of the Iliac Artery Rupture due to Vascular Type Ehlers-Danlos Syndrome

症例は39歳男性．左腸骨動脈解離，破裂にて緊急で開腹人工血管置換を施行した．術後閉腹不能であり，術後8日目に一時的腹壁形成術（TAC）をComposix Mesh® と持続陰圧閉鎖（NPWT）を用いて施行した．初回術後19日目に術前にはなかった総肝動脈瘤破裂をきたし，緊急再開腹手術を施行した．その後再度Composix Meshをあてなおし再TACを施行した．腸管浮腫軽減と後腹膜血腫吸収が得られたため初回術後43日目に閉腹手術を施行した．Composix Meshは完全に除去した．Components Separation法と腹直筋前葉翻転法による自己組織のみでの閉腹が可能であった．初回術後106日目に独歩退院となった．遺伝子検査にてCOL3A1の変異が確認され血管型エーラスダンロス症候群（EDS）と診断された．腹部動脈破裂術後の長期閉腹不能例にComposix MeshとNPWTによるTACが有効であった．若年者の血管破綻は血管型EDSの可能性があり治療に難渋することが予想される．

Abstract WP187: Diagnostic Significance of Connective Tissue Dysplasia Signs in Patients With Cervical Artery Dissection

Introduction: Cervical artery dissection (CeAD) is the most frequent cause of ischemic stroke in young adults. It is suggested that connective tissue dysplasia (CTD) underlies in the arterial wall weakness predisposing to dissection. The aim : to elucidate CTD signs that have prognostic and diagnostic significance for CeAD. Methods: We examined 80 patients (mean age 38,5±13,5; 49 females, 61,2%) with CeAD, verified by MRI/MRA and 20 healthy volunteers (mean age 30,3±6,7; 12 females 60%). We assessed 48 signs selected from criteria of the vascular type of Ehlers-Danlos syndrome, Marfan syndrome, Beighton criteria of joint hypermobility and other. In addition we estimated arterial hypotension (≤100/70 mm Hg), and headache in the past history. Each sign was counted as present or absent, resulting in an individual CTD score. On the basis of linear regression analysis these signs were divided into major and minor signs. Results: CTD signs were found more frequently in CeAD patients than in the control (mean score 7,9 ± 3,6 vs 4,6 ± 2,5; p<0.0039). The following CTD signs were significantly more often in patients than in control: arterial hypotension (51% vs 20%, Р=0,018), extensive bruising (40% vs 10%, Р=0,016), widened atrophic scars (23% vs 0%, Р=0,02), headache in the past history (60% vs 35%, p=0,027) - major signs; translucent skin (29% vs 5%, Р=0,037), hight palate (20% vs 0%, Р=0,037), nasal bleeding (34% vs 15%, Р=0,044), blue sclera (20% vs 5%, Р=0,05), propensity to constipation (30% vs 0%, Р=0,05) - minor signs. If there were 4 major and 2 small signs logistic regression model gave 75% predictive value of dissection. The reliability of these signs was confirmed by ROC analysis (AUC 0,90 [95% CI 0,84-0,96], sensitivity - 86%, specificity - 85%). Conclusion: CTD signs are highly prevalent in patients with CeAD that is in accordance with our morphological data that arterial wall dysplasia is a main cause of spontaneous dissection. The presence of 4 major and 2 minor signs may be used to estimate the predisposition to CeAD and in some cases as additional argument at clinical diagnosis.

A critical analysis of the perioperative management of patients with Ehlers Danlos type IV (vascular) syndrome.

This article discusses the perioperative care needs of patients with Ehlers Danlos type IV (vascular) syndrome. Ehlers Danlos syndrome (EDS) is a heritable group of connective tissue disorders characterised by varying degrees of tissue, blood vessel and internal organ fragility as well as skin and joint hypermobility (De Paepe and Malfait 2012).

A Case of Acute Peritonitis Due to Perforation of the Sigmoid Colon Associated with Vascular-Type Ehlers-Danlos Syndrome

A Case of Acute Peritonitis Due to Perforation of the Sigmoid Colon Associated with Vascular-Type Ehlers-Danlos Syndrome

The Vascular Type Ehlers-Danlos Syndrome Diagnosed after Delivery

The Vascular Type Ehlers-Danlos Syndrome Diagnosed after Delivery

Understanding Vascular-Type Ehlers-Danlos Syndrome and Avoiding Vascular Complications

Vascular-type Ehlers-Danlos syndrome (EDS) is a rare inherited connective tissue disorder caused by a mutation in type III procollagen. It has the highest mortality rate among the six types of EDS. Patients with this syndrome often have typical medical histories and a characteristic physical examination. We present two patients with this rare disorder and highlight the diagnostic and treatment challenges.

A Case of Right Posterior Tibial Artery Rupture Suspected Vascular-type Ehlers-Danlos Syndrome Treated with Transcatheter Arterial Embolization

A Case of Right Posterior Tibial Artery Rupture Suspected Vascular-type Ehlers-Danlos Syndrome Treated with Transcatheter Arterial Embolization