Vascular Ehlers-Danlos Syndrome Research Articles

Traumatic False Passage During Nasogastric Tube Insertion and Spontaneous Small Bowel Perforation in a Patient With Vascular Ehlers-Danlos Syndrome: A Case Report

Traumatic False Passage During Nasogastric Tube Insertion and Spontaneous Small Bowel Perforation in a Patient With Vascular Ehlers-Danlos Syndrome: A Case Report

Vascular Ehlers-Danlos Syndrome: A Comprehensive Natural History Study in a Dutch National Cohort of 142 Patients.

Vascular Ehlers-Danlos syndrome (vEDS) is a rare connective tissue disorder with a high risk for arterial, bowel, and uterine rupture, caused by heterozygous pathogenic variants in COL3A1. The aim of this cohort study is to provide further insights into the natural history of vEDS and describe genotype-phenotype correlations in a Dutch multicenter cohort to optimize patient care and increase awareness of the disease. Individuals with vEDS throughout the Netherlands were included. The phenotype was charted by retrospective analysis of molecular and clinical data, combined with a one-time physical examination. A total of 142 individuals (50% female) participated the study, including 46 index patients (32%). The overall median age at genetic diagnosis was 41.0 years. More than half of the index patients (54.3%) and relatives (53.1%) had a physical appearance highly suggestive of vEDS. In these individuals, major events were not more frequent (P=0.90), but occurred at a younger age (P=0.01). A major event occurred more often and at a younger age in men compared with women (P<0.001 and P=0.004, respectively). Aortic aneurysms (P=0.003) and pneumothoraces (P=0.029) were more frequent in men. Aortic dissection was more frequent in individuals with a COL3A1 variant in the first quarter of the collagen helical domain (P=0.03). Male sex, type and location of the COL3A1 variant, and physical appearance highly suggestive of vEDS are risk factors for the occurrence and/or early age of onset of major events. This national multicenter cohort study of Dutch individuals with vEDS provides a valuable basis for improving guidelines for the diagnosing, follow-up, and treatment of individuals with vEDS.

Abdominal involvement as a primary manifestation of systemic or isolated gastrointestinal vasculitis

Systemic vasculitides can cause a wide variety of gastrointestinal manifestations (GI) ranging from mild and frequently nonspecific abdominal pains to potentially life-threatening bowel perforations. Vascular involvement in systemic vasculitides can affect any GI blood vessel, most commonly mesenteric, hepatic, or splenic arteries. Inflammatory changes affecting different layers of arterial vessel walls can lead to aneurysmatic dilatation or blood vessel occlusion with subsequent organ ischemia leading to mucosal ulcerations, GI bleeding, perforations, or bowel obstruction. While the presence of extraintestinal manifestations may aid in diagnosis, delays in making appropriate diagnoses and rapid initiation of glucocorticoid and immunosuppressive treatment can have detrimental consequences. Awareness of isolated gastrointestinal vasculitis is of particular importance as it frequently remains undiagnosed until end-stage organ damage becomes apparent. Vasculitis mimics such as vascular Ehlers-Danlos syndrome or fibromuscular dysplasia add another lay of complexity in approaching patients with suspected GI vasculitis and should always be carefully considered.

Successful management of splenic artery dissection after sigmoid colon perforation in vascular Ehlers–Danlos syndrome

BackgroundEhlers–Danlos syndrome (EDS) is a genetic disorder that causes fragility of the systemic connective tissues. Of the 13 subtypes, vascular EDS (vEDS) is associated with abnormalities in collagen production, resulting in arterial rupture and intestinal perforation. Herein, we report the case of a man with confirmed vEDS who survived a ruptured dissected splenic artery aneurysm triggered by perforation of the sigmoid colon.Case presentationA 48-year-old man presented to our hospital with sudden severe lower abdominal pain. The patient was genetically diagnosed with vEDS at the age of 43 years. Abdominal computed tomography (CT) showed fluid and free air surrounding the sigmoid colon. These findings suggested sigmoid colon perforation, and emergency surgery was needed. Hartmann’s procedure was performed. The resected specimen showed a 2-cm-sized depression around the perforation. Histopathological findings showed an abscess and exudate in the serosa of the perforation and thinning of the intrinsic muscular layer in the depressed area. The patient was doing well postoperatively; however, on the ninth postoperative day, sudden upper abdominal pain developed. CT revealed an intra-abdominal hemorrhage due to rupture of a dissecting splenic artery aneurysm. The aneurysm was not observed on preoperative CT and was distant from the surgical site. Urgent transcatheter arterial embolization was performed. Although embolization of the splenic artery was attempted during the procedure, the arterial dissection spread to the common hepatic artery. Moreover, the proper hepatic and gastroduodenal arteries were poorly visualized, probably due to vasospasm. Although complications associated with extensive embolization were a concern, embolization of the splenic and common hepatic arteries was necessary to save the patient’s life. After embolization, angiography showed that the left hepatic blood flow was maintained from the inferior phrenic artery, and the right hepatic inflow was maintained from the superior mesenteric artery via the peribiliary vascular plexus in the hilar area. The patient recovered well and was discharged on the 19th postoperative day.ConclusionsvEDS can cause arterial rupture after intestinal surgery. Therefore, careful post-operative management is necessary. Moreover, cooperation with interventional radiologists is important for prompt treatment of vascular complications.

The Impact of Pregnancy in Patients with Thoracic Aortic Disease: Epidemiology, Risk Assessment, and Management Considerations.

Thoracic aortic disease (TAD) poses substantial risks during pregnancy, particularly for women with genetic conditions such as Marfan syndrome, Loeys-Dietz syndrome, and vascular Ehlers-Danlos syndrome. This review examines the epidemiology, risk assessment, and management of TAD in pregnancy. Preconception counseling is vital considering the hereditary nature of TAD and potential pregnancy-related complications. Genetic testing and imaging surveillance aid in risk assessment. Medical management, including beta-blockade and strict blood pressure control, is essential throughout pregnancy. Surgical interventions may be necessary in certain cases. A multidisciplinary approach involving cardiologists, obstetricians, cardiac surgeons, anesthesiologists, and other specialists with expertise in cardio-obstetrics is essential for optimal outcomes. Patient education and shared decision-making play vital roles in navigating the complexities of TAD in pregnancy and improving maternal and neonatal outcomes.

A81 GASTROINTESTINAL (GI) FEATURES OF HYPERMOBILE EHLERS-DANLOS SYNDROME (HEDS) AND HYPERMOBILITY SPECTRUM DISORDER (HSD): A SCOPING REVIEW

Abstract Background Ehlers-Danlos syndromes (EDS) are a varied group of hereditable connective tissue disorders (HCTD) typified by skin, joint and vascular features, along with less well-recognized features of chronic pain, immunological dysfunction and chronic GI symptoms. The latest EDS classification (2017) lists 13 EDS types and 19 genetic factors but there is no identified genetic basis for hEDS, the most common type and the most-commonly associated with GI symptoms. There is a need for robust data on the prevalence of GI symptoms and diagnoses in hEDS and HSD. Aims To investigate the extent of evidence on GI symptom prevalence and methods used to establish GI diagnoses in patients with hEDS and HSD. Methods Following the JBI (Joanna Briggs Institute) guide for scoping reviews, a systematic search of Ovid Medline, Embase and Cochrane Library retrieved scoping and systematic reviews, published in English (1974 – Sept 2023), reporting GI symptom prevalence, assessment and complications in EDS or HSD. Abstracts of identified papers were reviewed by NC &amp; DB and discrepancies resolved by YY &amp; DA. As a scoping review, it required no statistical comparisons. Results Duplicate screening of 410 abstracts yielded 10 papers that met inclusion criteria: 1 scoping and 9 systematic reviews. Four systematic reviews reported GI surgical issues related to vascular EDS; none was evaluated further. Two papers reported, specifically, on GI symptoms in patients with postural tachycardia syndrome or eating disorders, some of whom had hEDS or HSD and two papers reported on multiple GI and non-GI symptoms associated with fibromyalgia or functional somatic symptoms. The final 2 papers reported on multiple GI and non-GI symptoms in patients with HSD or multiple EDS types, limited in the latter case to papers published after the latest EDS classification (2017). In general, GI symptoms were characterised as IBS-like symptoms (Rome III or Rome IV) or as typical GI symptoms but without using a validated symptom questionnaire. Conclusions There are few data on GI symptom prevalence in hEDS or HSD and no standardised methods for identifying or characterizing GI symptoms or function in hEDS. The evaluation of GI function and symptoms in EDS is hampered by the absence of a definitive genetic or diagnostic test for hEDS or HSD and by changes in EDS classification over the last 50 years. There is a need for targeted systematic reviews of the prevalence of various GI symptoms in hEDS individuals and of relevant diagnostic methods, to guide further research into the causes of GI dysfunction in hEDS or HSD. Funding Agencies None

Generation of the human induced pluripotent stem cell line (IBKMOLi003-A) from PBMCs of a vascular Ehlers-Danlos syndrome (vEDS) patient carrying the heterozygous nonsense mutation c.430C > T (p.Q105*) in the COL3A1 gene

Ehlers-Danlos syndrome (EDS) belongs to a spectrum of rare heritable connective tissue disorders and is characterised by hyperextensibility, joint hypermobility and tissue fragility. Peripheral blood mononuclear cells (PBMCs) from a vascular EDS (vEDS) patient, known as the rarest EDS subtype, carrying a heterozygous nonsense mutation c.430C > T (p.Q105*) in the COL3A1 gene, which is essential for type III collagen synthesis, were reprogrammed into induced pluripotent stem cells (iPSCs). The generated iPSCs exhibit high expression of pluripotency-associated markers, possess trilineage differentiation capacity and reveal a normal karyotype. This novel patient-specific cell line enables in-depth pathophysiological studies of vEDS.

Anesthetic Management of Emergency Surgery for a Patient with Vascular Ehlers Danlos Syndrome (Type IV): A Case Report

Ehlers-Danlos syndrome (EDS) is a very rare genetic disorder characterized by defects in the production of connective tissue. Among them, vascular EDS is the subtype known to have the worst prognosis due to fragile blood vessels. Accordingly, we would like to report a case report of a patient with vascular EDS with a review of the literature on possible massive transfusion and anesthesiological problems. Patients with vascular EDS have very weak blood vessels and tissues that are easily broken. So there is a high possibility of unexpected massive bleeding during emergency surgery in these patients. Therefore, the anesthesiologist should be fully prepared for the possibility of massive blood loss, keeping in mind the possibility of damage to large blood vessels. The central vein must be secured using ultrasound, sufficient blood and fluids must be prepared, and equipment capable of rapid administration must be perfectly prepared before the start of operation.

Despite celiprolol therapy, patients with vascular Ehlers–Danlos syndrome remain at risk of vascular events: A 12-year experience in an Italian referral center

Background: Vascular Ehlers–Danlos syndrome (vEDS) is an inherited connective tissue disorder characterized by arterial fragility. Celiprolol has been suggested to significantly reduce rates of vascular events in this setting, though real-world evidence is limited. The aim of this study was to report our experience with celiprolol therapy in vEDS management. Methods: Patients with a genetically confirmed diagnosis of vEDS who were referred for outpatient consultation at the Brescia University Hospital between January 2011 and July 2023 were included. At each visit, patients’ medical history, results of vascular imaging, and office blood pressure measurements were recorded. Celiprolol therapy was progressively titrated to the maximum tolerated dose of up to 400 mg daily, according to the patients’ tolerance. Results: Overall, 26 patients were included. Female sex was prevalent (62%). Mean (SD) age was 37 (16) years. Follow-up duration was 72 (41) months. At the last follow-up visit, all patients were on celiprolol therapy, 80% of whom were taking the maximum recommended dose. The yearly risk of symptomatic vascular events was 8.8%, the majority of which occurred after reaching the maximum recommended dose of celiprolol. No significant predictor of symptomatic vascular events was identified among patients’ clinical characteristics. Conclusion: In our cohort, rates of celiprolol use were high and the drug was well tolerated overall. Nonetheless, the risk of symptomatic vascular events remained nonnegligible. Future studies should identify reliable predictors of major adverse events and explore additional therapeutic strategies that could further lower the risk of life-threatening events in this population.

COL3A1 mutations in spontaneous coronary artery dissection

Abstract Background Spontaneous coronary artery dissection (SCAD) affects mainly women with a mean age of 51 years.(1) Predicted damaging variants in connective tissue disease (CTD) genes have been found in a subset of patients with SCAD, however in some cases the typical phenotype associated with these conditions is lacking. Variants in the COL3A1 gene, on chromosome 2 encoding type III collagen, appear to be one of the most frequently reported in SCAD. Mutations in COL3A1 alter the production and structure of type III procollagen and weaken connective tissues, including blood vessel walls and cause vascular Ehlers-Danlos Syndrome (vEDS).(2) Purpose Systematically determine the known cases of SCAD with COL3A1 likely pathogenic/pathogenic (LP/P) variants to highlight COL3A1 as a SCAD-causative gene, in a subset of SCAD cases. Methods We searched PubMed using search terms "spontaneous coronary artery dissection" AND COL3A1, "spontaneous coronary artery dissection" AND "vascular Ehlers-Danlos syndrome", "spontaneous coronary artery dissection" AND genetics. We also searched the ClinVar database using COL3A1 [gene] and the following stipulations: clinical significance limited to pathogenic or likely Pathogenic; molecular consequence limited to frameshift, missense or nonsense, and review status limited to multiple submitters or at least one star. The COL3A1 variants identified were reclassified using American College of Medical Genetics (ACMG) criteria. Fisher's exact test was used for statistical comparisons. Results There were 42 published cases of SCAD with a LP/P mutation in COL3A1. Of the 42 published cases, there were two cases published twice. Using updated ACMG criteria, three cases were reclassified to variant of uncertain significance (VUS), from LP/P. This resulted in 37 unique cases of SCAD with LP/P variants using ACMG criteria. Of the cases with LP/P mutations where sex was known, 11/33 cases (35%) were male, higher than that reported in a large, published cohort where 86/750 SCAD cases (11.5%) were male (1) (p = 0.001129, 95% CI 0.115876 0.614725). Most SCAD cases with a COL3A1 LP/P mutation in whom age was reported, were under age 40 years (23/31, 74%), proportionally more cases when compared to a cohort of SCAD cases where 82/460 SCAD cases were under age 40 years (18%) (p value = 8.782e-11, 95% CI 0.02837315 0.18361793). Of the variant types reported (16/37), the majority were single nucleotide variants with one copy number variation (duplication). Conclusion While no one gene carries damaging variants in a large proportion of SCAD cases, COL3A1 variants have been found in a number of people with SCAD. Patients presenting with SCAD under 40 years and particularly males should be screened for pathogenic variants in aortopathy and connective tissue genes, such as COL3A1.Table:SCAD with COL3A1 LP/P variants 1TableSCAD with COL3A1 LP/P variants 2

Abstract 15404: Exercise and Sports Participation is Associated With Improved Quality of Life in Young Patients With Heritable Thoracic Aortic Disease

Introduction: Traditionally, patients with heritable thoracic aortic disease (HTAD) have been restricted from competitive sports due to concerns over acute aortic dissection. Patients with HTAD also exhibit lower quality of life (QOL) and physical fitness than general populations. Murine data suggests exercise improves aortic health and does not contribute to aortic enlargement. Hypothesis: Exercise and competitive sports participation will be associated with improved QOL in HTAD patients. Aims: Investigate the effect of lifetime exercise ‘dose’ and competitive sports participation on QOL in patients aged 15-35 with syndromic HTAD [Marfan syndrome (MS), Loeys-Dietz syndrome (LDS), vascular Ehlers-Danlos syndrome (vEDS)] and non-syndromic HTAD. Methods: This cross-sectional study employed a questionnaire to assess lifetime exercise exposure and utilized the PedsQL QOL Inventory. We developed an Exercise Score (ES) to quantify lifetime exercise exposure based on questionnaire results (3 points for competitive sports season, 1 point for recreational sport season. Questionnaires were completed via telephone interview with complimentary medical chart review. Results: Of the forty patients enrolled, the mean age was 26 years. The diagnosis was MS in 82.5%. Despite 87.5% of patients being restricted by their cardiologist, 65% reported competitive sports participation and 92.5% reported some lifetime recreational exercise. The median ES for our population was 19. Participants with an ES greater than the median had a significantly better total QOL score compared to participants with an ES below the median (78 vs 65, p=0.03). There was no difference in aortic size or need for surgical intervention between those above and below the median ES. This also held true for those who did and did not participate in competitive sports. There was a strong positive correlation between the amount of current exercise (days-per-week) and total QOL score (corr=0.55, p&lt;0.001). Conclusions: Increased lifetime exercise exposure and current physical activity levels were associated with improved QOL in young adults with HTAD. There did not appear to be a detrimental effect of exercise on aortic size or need for surgical intervention.

Deciphering disease signatures and molecular targets in vascular Ehlers-Danlos syndrome through transcriptome and miRNome sequencing of dermal fibroblasts

Vascular Ehlers-Danlos syndrome (vEDS) is a severe connective tissue disorder caused by dominant mutations in the COL3A1 gene encoding type III collagen (COLLIII). COLLIII is primarily found in blood vessels and hollow organs, and its deficiency leads to soft connective tissues fragility, resulting in life-threatening arterial and organ ruptures. There are no current targeted therapies available. Although the disease usually results from COLLIII misfolding due to triple helix structure disruption, the underlying pathomechanisms are largely unknown. To address this knowledge gap, we performed a comprehensive transcriptome analysis using RNA- and miRNA-seq on a large cohort of dermal fibroblasts from vEDS patients and healthy donors. Our investigation revealed an intricate interplay between proteostasis abnormalities, inefficient endoplasmic reticulum stress response, and compromised autophagy, which may significantly impact the molecular pathology. We also present the first detailed miRNAs expression profile in patient cells, demonstrating that several aberrantly expressed miRNAs can disrupt critical cellular functions involved in vEDS pathophysiology, such as autophagy, proteostasis, and mTOR signaling. Target prediction and regulatory networks analyses suggested potential interactions among miRNAs, lncRNAs, and candidate target genes linked to extracellular matrix organization and autophagy-lysosome pathway. Our results highlight the importance of understanding the functional role of ncRNAs in vEDS pathogenesis, shedding light on possible miRNAs and lncRNAs signatures and their functional implications for dysregulated pathways related to disease. Deciphering this complex molecular network of RNA interactions may yield additional evidence for potential disease biomolecules and targets, assisting in the design of effective patient treatment strategies.

[A Case of Left Renal Cell Carcinoma with Renal Arteriovenous Fistula and Multiple Vascular Malformation Undergoing Nephrectomy].

A 69-year-old woman was referred to our hospital for the treatment of a left renal tumor found by computed tomography (CT) during examination for microscopic hematuria. Contrast-enhanced CT showed a 5 cm tumor in the inferior pole of the left kidney. Left renal cell carcinoma (RCC) (cT1bN0M0) was suspected. In addition, the left renal and gonadal veins were dilated and enhanced in an arterial phase; renal arteriovenous fistula (RAVF) was suspected. Moreover, there were multiple focal arterial dilatations, suggesting the presence of multiple vascular malformation. Hereditary aortic disease, including vascular Ehlers-Danlos syndrome (vEDS), was a concern. In general, surgery is not recommended for patients with vEDS, due to vascular fragility. As such, a panel analysis of genes for hereditary aortic diseases, including vEDS, was performed; no pathogenic variants in candidate genes including COL3A1 were identified. After detailed discussions with the patient, she underwent a left nephrectomy, following transcatheter arterial embolization (TAE) of the left renal artery. We prepared a balloon catheter for aortic occlusion as a preventative measure for massive bleeding; this was not the case, as only a small amount of intraoperative bleeding occurred. Thus, the nephrectomy was performed successfully without using the balloon catheter. The patient recovered uneventfully and was discharged on day 8. Pathological examination showed clear-cell RCC (pT1a) and a RAVF near the tumor. Herein we report this case of left RCC with RAVF and multiple arterial malformation, which was successfully managed by evaluating preoperative risks with a genetic test, followed by TAE of the renal artery and open nephrectomy.

PB1416 Challenge in the Investigation of Patients with Bleeding: Delayed Diagnosis of Vascular Ehlers-Danlos Syndrome

PB1416 Challenge in the Investigation of Patients with Bleeding: Delayed Diagnosis of Vascular Ehlers-Danlos Syndrome

PB0212 Patient with Spontaneous and Severe Bleeding Episodes Diagnosed of Vascular Ehlers-Danlos Syndrome with a De Novo Pathogenic Variant

PB0212 Patient with Spontaneous and Severe Bleeding Episodes Diagnosed of Vascular Ehlers-Danlos Syndrome with a De Novo Pathogenic Variant

Vertebral Tortuosity Is Associated With Increased Rate of Cardiovascular Events in Vascular Ehlers-Danlos Syndrome.

Background Arterial tortuosity is associated with adverse events in Marfan and Loeys-Dietz syndromes but remains understudied in Vascular Ehlers-Danlos syndrome. Methods and Results Subjects with a pathogenic COL3A1 variant diagnosed at age <50 years were included from 2 institutions and the GenTAC Registry (National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions). Height-adjusted vertebral artery tortuosity index (VTI-h) using magnetic resonance or computed tomography angiography was calculated. Associations between VTI-h and outcomes of (1) cardiovascular events (arterial dissection/rupture, aneurysm requiring intervention, stroke), or (2) hollow organ collapse/rupture at age <50 years were evaluated using receiver operator curve analysis (using outcome by age 30 years) and mixed-effects Poisson regression for incidence rate ratios. Of 65 subjects (54% male), median VTI-h was 12 (interquartile range, 8-16). Variants were missense in 46%, splice site in 31%, and null/gene deletion in 14%. Thirty-two subjects (49%) had 59 events, including 28 dissections, 5 arterial ruptures, 4 aneurysms requiring intervention, 4 strokes, 11 hollow organ ruptures, and 7 pneumothoraces. Receiver operator curve analysis suggested optimal discrimination at VTI-h ≥15.5 for cardiovascular events (sensitivity 70%, specificity 76%) and no association with noncardiovascular events (area under the curve, 0.49 [95% CI, 0.22-0.78]). By multivariable analysis, older age was associated with increased cardiovascular event rate while VTI-h ≥15.5 was not (incidence rate ratios, 1.79 [95% CI, 0.76-4.24], P=0.185). However, VTI-h ≥15.5 was associated with events among those with high-risk variants <40 years (incidence rate ratios, 4.14 [95% CI, 1.13-15.10], P=0.032), suggesting effect modification by genotype and age. Conclusions Increased arterial tortuosity is associated with a higher incidence rate of cardiovascular events in Vascular Ehlers-Danlos syndrome. Vertebral tortuosity index may be a useful biomarker for prognosis when evaluated in conjunction with genotype and age.

Evaluating Variation in the Cardiac Management of Children with Hereditary Thoracic Aortic Disease in the United States.

Hereditary thoracic aortic diseases (HTAD) such as Marfan syndrome (MFS), Loeys-Dietz syndrome (LDS), and vascular Ehlers-Danlos syndrome (VEDS) frequently result in complex cardiovascular pathology that can lead to premature death. However, given limited research and lack of detailed pediatric management guidelines, practice in the U.S. is largely guided by personal experience and/or advice from other professionals. A REDCap survey was composed that covered topics including genetic testing, imaging, and medication choice (all in children), among others. After piloting, the survey was distributed via email and advertised on PediHeartNet. Email addresses of providers were obtained through an established aortic research collaborative and a clinic directory offered through The Marfan Foundation. There were 64 survey responses (pediatric cardiologists 66%; geneticists 13%, genetic counselors 6%; the remaining 15% was comprised of a combination of cardiothoracic surgeons, adult cardiologists, adult congenital specialists, combined cardiology and genetics specialist, nurse practitioners, physician assistants, and nurse coordinators). The most supported indication for genetic evaluation in a child with mild aortic root dilation was family history of thoracic aortic dissection (100%), in contrast to mild root dilation with no other HTAD features (39% supported, 45% did not, 15% saying it would depend on other factors). The majority would start medical therapy in MFS at an aortic root z-score of 2, however differences existed regarding medication preferences for initiation (47% angiotensin receptor blockers, 36% beta blockers, 17% would not or cannot prescribe medication/defer medication choice to another provider). Variation existed for cross-sectional imaging indications and modality and for exercise restrictions, although on average respondents were more lenient than the Bethesda guidelines. While there are areas of general agreement in the cardiac management of children with HTAD, there are also several areas of considerable variation. This highlights the need for additional study in these areas with the ultimate goal of creating consensus guidelines.

C4 (Clinical Case) Vascular Ehlers-Danlos Syndrome in the Paediatric Population: A Case Report of an Internal Bleed Caused by Ruptured Pseudoaneurysm

Abstract Introduction/Background Ehlers-Danols syndrome (EDS) is a connective tissue disease characterized by joint hypermobility, skin hyperextensibility and tissue fragility. EDS has six types. Type IV EDS: vascular EDS (vEDS), is rare but also the most malignant. Case Description We report a 15-year-old boy with a previous history of spontaneous colon perforation and two left shoulder dislocations. He presented with sudden onset abdominal pain, vomiting, dizziness, and lethargy with a Glasgow coma scale of 13. His abdomen was soft but mildly tender. He had a capillary refill of 3 seconds with cold extremities, was found to be in a hypotensive shock state requiring resuscitation with fluids and inotropes, as well as intubation and mechanical ventilation. His hemoglobin dropped by 30 g/L in 6 hours. Therefore, an abdominal ultrasound was done, revealing an intrabdominal hematoma. CT scan of the abdomen confirmed a ruptured fusiform pseudoaneurysm of the accessory left hepatic artery. This was successfully managed by coil embolization, see F1 and F2, below. Genetic workup was positive for the pathogenic COL3A1 gene that presents phenotypically as Ehlers-Danlos syndrome, particularly type IV. Discussion COL3A1 encodes pro-alpha1 chains of type III collagen. Inheritance is autosomal-dominant. It can present as a de novo variant with a negative family history, as was the situation for our patient. Estimated affected people with de novo variant vEDS is 33%-50%. Clinical diagnosis of vEDS involves one major and several minor criteria (2017). Major criteria include arterial aneurysms, dissection, or rupture; intestinal rupture; uterine rupture during pregnancy; family history of vEDS. Minor criteria include easy bruising; thin skin and visible veins; facial characteristics including prominent eyes, narrow nasal bridge, thin lips; club foot, congenital hip dislocation; inguinal hernia and pneumothorax. Our patient had two elements from the major criteria: arterial pseudoaneurysm and intestinal rupture. Conclusion vEDS has high morbidity and mortality due to the risk of spontaneous internal organ/vessel injury. This can be mitigated by increased awareness of systemic manifestations of vEDS and a high index of suspicion by both primary care and emergency physicians. Once diagnosed, surveillance is crucial, including regular blood pressure monitoring, frequent non-invasive imaging to identify emerging vascular lesions, and pregnancy counselling for potential uterine rupture and avoiding trauma, collision sports, and lifting heavy items.

Open repair of an infected abdominal aortic aneurysm in a patient with vascular Ehlers-Danlos syndrome.

Open repair of an infected abdominal aortic aneurysm in a patient with vascular Ehlers-Danlos syndrome.

Genetic Basis, New Diagnostic Approaches, and Updated Therapeutic Strategies of the Syndromic Aortic Diseases: Marfan, Loeys-Dietz, and Vascular Ehlers-Danlos Syndrome.

Syndromic aortic diseases (SADs) encompass various pathological manifestations affecting the aorta caused by known genetic factors, such as aneurysms, dissections, and ruptures. However, the genetic mutation underlying aortic pathology also gives rise to clinical manifestations affecting other vessels and systems. As a consequence, the main syndromes currently identified as Marfan, Loeys-Dietz, and vascular Ehlers-Danlos are characterized by a complex clinical picture. In this contribution, we provide an overview of the genetic mutations currently identified in order to have a better understanding of the pathogenic mechanisms. Moreover, an update is presented on the basis of the most recent diagnostic criteria, which enable an early diagnosis. Finally, therapeutic strategies are proposed with the goal of improving the rates of patient survival and the quality of life of those affected by these SADs.