• Genetic connective tissue disorder
• ICD complication
• RV perforation
• Recurrent pericarditis
• Vascular Ehlers-Danlos syndrome

• carotid-cavernous fistula
• cavernous sinus
• proptosis

• Bulk RNA-seq
• Cell-matrix interactions
• Extracellular matrix
• Mechanical properties

• Animals
• Aorta/metabolism
• Aorta/growth & development
• Mice
• Gene Expression Regulation, Developmental
• Elastin/metabolism
• Elastin/genetics
• Transcription, Genetic
• Animals, Newborn
• Biomechanical Phenomena
• Gene Expression Profiling
• Mice, Inbred C57BL

• R01 HL155105 NHLBI NIH HHS

• Humans
• Eye Diseases/diagnostic imaging
• Eye Diseases/etiology
• Thoracic Diseases/diagnostic imaging
• Diagnosis, Differential
• Multimodal Imaging/methods

• Aortic aneurysm
• Aortic dissection
• Genetic aortopathy
• Genetic arteriopathy
• Heritable thoracic aortic disease
• Vascular surgery

• United States
• Humans
• Aorta, Thoracic/surgery
• Aortic Aneurysm
• Aortic Diseases/genetics
• Aortic Diseases/surgery
• Aortic Aneurysm, Thoracic/diagnosis
• Aortic Aneurysm, Thoracic/genetics
• Aortic Aneurysm, Thoracic/surgery

• caroticocavernous fistula
• joint hypermobility
• proptosis
• skin hyperelasticity
• vascular ehlers danlos syndrome

• Aortopathy
• Bentall procedure
• David procedure
• Yacoub procedure
• aortic valve surgery
• cardiac surgery
• valve-sparing root replacement surgery

• Humans
• Syndrome
• Heart Valve Prosthesis Implantation/adverse effects
• Heart Valve Prosthesis Implantation/methods
• Aorta, Thoracic/surgery
• Dilatation/adverse effects
• Aortic Valve/surgery
• Aortic Diseases/surgery
• Postoperative Complications/epidemiology
• Postoperative Complications/etiology
• Treatment Outcome
• Aortic Valve Insufficiency/surgery
• Retrospective Studies

• FS/CRTF/22/24312 British Heart Foundation
• FS/CRTF/22/24328 British Heart Foundation

• Diagnosis
• Diagnostic value
• Internal medicine
• Non-dermatology medical specialties
• Skin biopsy

• (+)catechin fuchsin
• collagen
• elastic fibers
• histomorphometry
• inherited connective tissue disease
• picrosirius red
• skin

Isolated small bowel perforation is low in the differential diagnosis of abdominal pain in the young, relatively healthy patient. It is, however, a rare manifestation of type IV (vascular) Ehlers-Danlos syndrome (EDS). In addition, there is no general consensus on the management of GI manifestations in patients with type IV EDS. We present the case of a 31-year-old male with history of type IV EDS, presenting with acute onset abdominal pain. Imaging was notable for intra-abdominal free air and thickened loops of small bowel in the pelvis. The patient underwent exploratory laparotomy with resection of the small bowel perforation with enteroenteric anastomosis. In our literature review, we evaluated gastrointestinal manifestations observed in patients with type IV EDS, management recommendations and potential complications to be mindful of in this population.

• arterial aneurysm
• arterial dissection
• vascular endothelial growth factor (VEGF)

The Ehlers-Danlos syndromes (EDS) are rare connective tissue disorders consisting of 13 subtypes with overlapping features including joint hypermobility, skin and generalized connective tissue fragility. Classical EDS (cEDS) is principally caused by heterozygous COL5A1 or COL5A2 variants and rarely by the COL1A1 p.(Arg312Cys) substitution. Current major criteria are (1) skin hyperextensibility plus atrophic scars and (2) generalized joint hypermobility (gJHM). Minor criteria include additional mucocutaneous signs, epicanthal folds, gJHM complications, and an affected first-degree relative. Minimal criteria prompting molecular testing are major criterion 1 plus either major criterion 2 or 3 minor criteria. In addition to these features, the clinical picture also involves multiple organ systems, but large-scale cohort studies are still missing. This study aimed to investigate the multisystemic involvement and natural history of cEDS through a cross-sectional study on a cohort of 75 molecularly confirmed patients evaluated from 2010 to 2019 in a tertiary referral center. The diagnostic criteria, additional mucocutaneous, osteoarticular, musculoskeletal, cardiovascular, gastrointestinal, uro-gynecological, neuropsychiatric, and atopic issues, and facial/ocular features were ascertained, and feature rates compared by sex and age.

Our study confirms that cEDS is mainly characterized by cutaneous and articular involvement, though none of their hallmarks was represented in all cases and suggests a milder multisystemic involvement and a more favorable natural history compared to other EDS subtypes. Abnormal scarring was the most frequent and characteristic sign, skin hyperextensibility and gJHM were less common, all without any sex and age bias; joint instability complications were more recurrent in adults. Some orthopedic features showed a high prevalence, whereas the other issues related to the investigated organ systems were less recurrent with few exceptions and age-related differences.

Our findings define the diagnostic relevance of cutaneous and articular features and additional clinical signs associated to cEDS. Furthermore, our data suggest an update of the current EDS nosology concerning scarring that should be considered separately from skin hyperextensibility and that the clinical diagnosis of cEDS may be enhanced by the accurate evaluation of orthopedic manifestations at all ages, faciocutaneous indicators in children, and some acquired traits related to joint instability complications, premature skin aging, and patterning of abnormal scarring in older individuals.

• Atrophic scars
• COL1A1
• COL5A1
• COL5A2
• Classical Ehlers-Danlos syndrome
• Joint hypermobility
• Multisystemic involvement
• Natural history
• Nosology
• Skin hyperextensibility

• Arterial tortuosity
• Marfan syndrome
• Risk stratification
• Visceral arteries

• communication
• genetic diagnosis disclosure
• lived experience
• multidisciplinary
• vascular ehlers-danlos syndrome

Bilateral cavernous carotid aneurysm (CCA) is a rare entity. Its association with connective tissue disorder makes the diagnosis and treatment of symptomatic patient an enigma. We present a case report of a 25-year-old female medical student presented to us with bilateral spontaneous atypically symptomatic CCA with incidentally diagnosed case of Ehlers–Danlos syndrome. Both surgical and endovascular options of treatment were weighed and were ultimately treated satisfactorily by high-flow bypass with carotid artery ligation with an insurance bypass.

• Bilateral cavernous carotid aneurysm
• Ehlers–Danlos syndrome
• high-flow bypass
• insurance bypass

• Ehlers–Danlos syndrome
• Heritable connective tissue disorders
• Heterogeneity

• pyelonephritis
• renal infarction
• vascular Ehlers–Danlos syndrome

• Ehlers-danlos
• aneurysm
• vascular

Vascular Ehlers-Danlos syndrome (vEDS) is a rare condition characterized by connective tissue fragility. Direct spontaneous carotid-cavernous fistula (sCCF) is reportedly pathognomonic of vEDS. We conducted this study to understand the possible mechanisms of occurrence of sCCF in this subset of patients.

We conducted a retrospective analysis of a monocentric vEDS cohort along with a literature review regarding sCCF in this condition.

Of 133 patients regularly followed in our centre between 2000 and 2017, 13 (9.8%) had a diagnosis of direct sCCF (92.3% female, median age 33.0 years, interquartile range (IQR) [26.0–39.5]). There were 7 Glycine missense and 6 splice-site variants but no variant leading to haploinsufficiency. The literature search identified 97 vEDS patients with direct sCCF (79.4% female, 7.2% sex not reported, median age 31.0 years, IQR [24.0–39.0]). Increased carotid circumferential wall stress, higher carotid distensibility and lower carotid intima-media thickness could contribute to a higher risk for direct sCCF in vEDS. There is no predictive factor for the occurrence of sCCF apart from female sex in vEDS.

In vEDS, anatomical and pathophysiological features of the intra-cavernous internal carotid artery make it prone to shunting in the cavernous sinus, due either to a spontaneous rupture or to a spontaneous dissection with pseudoaneurysm formation. Direct sCCF in seemingly healthy young individuals should be highly suggestive of vEDS and prompt further investigation.

• Carotid-cavernous fistula
• Genetics
• Neurology
• Neuroophthalmology
• Pathophysiology
• Rare vascular disease
• Vascular Ehlers-Danlos syndrome

• Adult
• Aortic Dissection
• Angiography, Digital Subtraction
• Humans
• Intracranial Aneurysm/complications
• Intracranial Aneurysm/diagnosis
• Male
• Subarachnoid Hemorrhage/etiology
• Tomography, X-Ray Computed

• Connective tissue
• Ehlers-Danlos
• Genetic diseases
• Hyperlaxité articulaire
• Hyperélasticité cutanée
• Joint hypermobility
• Maladies génétiques
• Maladies métaboliques
• Matrice extracellulaire
• Metabolic diseases
• Protéoglycans
• Skin fragility
• Skin hyperextensibility
• Syndromes d’Ehlers-Danlos
• Tissu conjonctif

• Cohort
• incidence
• intracranial aneurysm
• nationwide
• risk factors
• subarachnoid hemorrhage

• CT, computed tomography
• CTA, computed tomographic angiography
• MRA, Magnetic resonance angiography
• MRI, magnetic resonance imaging

• connective tissue disease
• splenic rupture
• vascular ehlers-danlos syndrome

• AHA Scientific Statements
• cerebral aneurysm
• epidemiology
• imaging
• natural history
• outcome
• risk factors
• treatment

• Disease Management
• Female
• Health Personnel/standards
• Humans
• Intracranial Aneurysm/diagnosis
• Intracranial Aneurysm/epidemiology
• Intracranial Aneurysm/therapy
• Male
• Stroke/diagnosis
• Stroke/epidemiology
• Stroke/therapy
• United States/epidemiology

• Ehlers–Danlos syndrome
• Pneumothorax
• Total pleural covering technique

• Ehlers-Danlos Syndrome/complications
• Ehlers-Danlos Syndrome/diagnosis
• Humans
• Male
• Pleura/surgery
• Pneumothorax/etiology
• Pneumothorax/surgery
• Recurrence
• Young Adult

Fibromuscular dysplasia (FMD) is a nonatherosclerotic, noninflammatory angiopathy of unknown cause affecting medium-sized (most commonly renal) arteries and causing renovascular hypertension. The most common medial multifocal type of FMD (with the “string of beads” appearance) is more than four times more prevalent in females than in males. FMD accounts for up to 10% of cases of renovascular hypertension. Compared with patients with atherosclerotic renal artery stenosis, patients with FMD are younger, have fewer risk factors for atherosclerosis, and a lower occurrence of atherosclerosis in other vessels. The etiology is multifactorial, including vessel wall ischemia and smoking, as well as hormonal and genetic factors. Intra-arterial digital subtraction angiography is still the gold standard for exclusion or confirmation of renal artery stenosis caused by FMD, at least in young patients, who more often have lesions in branches of the renal artery. For FMD patients with atherosclerosis and those who are older (>50–55 years), significant renal artery stenosis may be confirmed or excluded with ultrasonography. The FMD lesion is typically truncal or distal, whereas atherosclerotic lesions are more often proximal or ostial. Treatment options are medical, endovascular (percutaneous transluminal renal angioplasty [PTRA]), and surgical. Invasive treatment should be considered when hypertension cannot be controlled with antihypertensive drugs and in patients with impaired renal function or ischemic nephropathy. PTRA has become the treatment of choice and normally yields good results, especially in unifocal disease and young patients. Pressure gradients are normally completely abolished, and there is no indication for stent placement. Surgical revascularization is indicated after PTRA complications; thrombosis, perforation, progressive dissection, repeated PTRA failure or restenosis. Centralization of handling is recommended.

• arterial hypertension
• fibromuscular dysplasia
• percutaneous transluminal renal angioplasty
• renal artery stenosis
• renal artery surgery

• Arterial dissection
• Arterial rupture
• Axial CT
• Back pain
• Collagen vascular disease
• Common iliac artery dissection
• Ectasia
• Ehlers-Danlos Syndrome
• Elastin
• Hypovolemic shock
• Iliac artery
• Perforation
• Retroperitoneal hematoma
• Retroperitoneal hemorrhage
• Vascular fragility
• Vascular imaging
• Vascular type Ehlers-Danlos Syndrome

• Adult
• Diagnosis, Differential
• Ehlers-Danlos Syndrome/complications
• Ehlers-Danlos Syndrome/genetics
• Ehlers-Danlos Syndrome/pathology
• Fatal Outcome
• Hemorrhage/etiology
• Humans
• Iliac Artery/diagnostic imaging
• Iliac Artery/pathology
• Iliac Artery/surgery
• Imaging, Three-Dimensional
• Male
• Prognosis
• Recurrence
• Retroperitoneal Space
• Rupture, Spontaneous/complications
• Rupture, Spontaneous/diagnostic imaging
• Rupture, Spontaneous/surgery
• Tomography, X-Ray Computed

• Angiography
• Coil
• Dissection
• Fistula
• Vein

• Ehlers-Danlos syndrome
• Type III
• chronic pain
• connective tissue disorders
• disability
• hypermobility
• joint laxity
• lived experience

• Ehlers–Danlos syndrome
• iliac artery aneurysm
• spontaneous arterial dissection

• Aneurysm
• Aorta
• Gene
• Mechanotransduction
• Mutation

Carotid cavernous sinus fistulas are abnormal communications between the carotid system and the cavernous sinus. Several classification schemes have described carotid cavernous sinus fistulas according to etiology, hemodynamic features, or the angiographic arterial architecture. Increased pressure within the cavernous sinus appears to be the main factor in pathophysiology. The clinical features are related to size, exact location, and duration of the fistula, adequacy and route of venous drainage and the presence of arterial/venous collaterals. Noninvasive imaging (computed tomography, magnetic resonance, computed tomography angiography, magnetic resonance angiography, Doppler) is often used in the initial work-up of a possible carotid cavernous sinus fistulas. Cerebral angiography is the gold standard for the definitive diagnosis, classification, and planning of treatment for these lesions. The endovascular approach has evolved as the mainstay therapy for definitive treatment in situations including clinical emergencies. Conservative treatment, surgery and radiosurgery constitute other management options for these lesions.

• Cavernous sinus
• Carotid cavernous sinus fistula
• Endovascular treatment

There are many genetic syndromes associated with the aortic aneurysmal disease which include Marfan syndrome (MFS), Ehlers-Danlos syndrome (EDS), Loeys-Dietz syndrome (LDS), familial thoracic aortic aneurysms and dissections (TAAD), bicuspid aortic valve disease (BAV), and autosomal dominant polycystic kidney disease (ADPKD). In the absence of familial history and other clinical findings, the proportion of thoracic and abdominal aortic aneurysms and dissections resulting from a genetic predisposition is still unknown. In this study, we propose the review of the current genetic knowledge in the aortic disease, observing, in the results that the causative genes and molecular pathways involved in the pathophysiology of aortic aneurysm disease remain undiscovered and continue to be an area of intensive research.