Change in gliding properties of the iliotibial tract in hypermobile Ehlers-Danlos Syndrome.

PURPOSE: Fascial changes in hypermobile Ehlers-Danlos syndrome (hEDS), a heritable connective tissue disorder, can be used visualized with sonoelastography. The purpose of this study was to explore the inter-fascial gliding characteristics in hEDS. METHODS: In 9 subjects, the right iliotibial tract was examined with ultrasonography. Tissue displacements of the iliotibial tract were estimated from ultrasound data using cross-correlation techniques. RESULTS: In hEDS subjects, shear strain was 46.2%, lower than those with lower limb pain without hEDS (89.5%) and in control subjects without hEDS and without pain (121.1%). CONCLUSION: Extracellular matrix changes in hEDS may manifest as reduced inter-fascial plane gliding.

ANATOMIC AND TOPOGRAPHIC CHANGES OF ANTERIOR SEGMENT STRUCTURES IN EHLERS-DANLOS SYNDROME PATIENTS WITH MYOPIA.

OBJECTIVE: The aim: Determination of anatomical and topographical relationships of the eyeball anterior segment structures to assess possible glaucoma development risk factors in SED patients with myopic refraction. PATIENTS AND METHODS: Materials and methods: Patients, aged from 10 to 34, have been examined since 2009. All the patients have undergone required medic and genetic examination as well as generally accepted ophthalmological one. Ultrasound biomicroscopy (UBM) has been performed using the VuMax II apparatus (Sonomed, USA) with a sensor frequency of 50 MHz. RESULTS: Results: Biomicroscopy found no symptoms such as pigment dispersion on the iris stroma, in the chamber anterior angle, iris transillumination and "Krukenberg's Spindle", which are characteristic for the ultrasound picture in pigment dispersion syndrome. CONCLUSION: Conclusions: 1. Clinical and functional study with the eyeballs mandatory ultrasound biomicroscopy have revealed functional space limitations for the structures of the iridociliary zone in patients with myopic type of eye structure in SED. 2. Detected congenital changes in the anterior segment structures (iridociliary cystic formations and residual mesodermal tissue) can lead to the emergence of intraocular blocks. 3. The research has identified conducive anatomical and topographic changes, which are likely to induce pigment dispersion syndrome or lead to the development of pigmentary glaucoma. 4. In our opinion, the UBM role in the early diagnosing and monitoring patients with SED syndrome is quite significant in terms of assessing the stability or dynamics of the changes received and possible complications. Ultrasound biomicroscopic scanning should be added to the list of necessary early diagnostic examinations to determine the markers and features of structures in SED.

Temporomandibular disorders, bite force and osseous changes of the temporomandibular joints in patients with hypermobile Ehlers-Danlos syndrome compared to a healthy control group.

BACKGROUND: Ehlers-Danlos syndrome (EDS) is a hereditary disorder that affects the connective tissue and collagen structures in the body characterised by joint hypermobility, skin hyperextensibility and tissue fragility. OBJECTIVE: The aim was to investigate temporomandibular disorders (TMD), bite force, teeth in occlusal contact and osseous changes of the temporomandibular joints (TMJs) in 26 patients with hypermobile EDS (hEDS), differentiated by a genetic test, compared to 39 healthy controls. METHODS: Clinical examination according to Diagnostic Criteria for Temporomandibular Disorders (DC/TMD), radiological examinations of the TMJs by cone-beam-computed tomographic (CBCT) scans, registration of bite force and teeth in occlusal contact was performed. Statistical analyses included Fisher's Exact Test, multiple logistic and linear regression models adjusted for age, gender and Body Mass Index (BMI). RESULTS: Single symptoms and signs of TMD occurred significantly more often in hEDS (p = .002; p = .001; p = .003; p = <.0001; p = .012) and maximum mouth opening was significantly smaller in hEDS compared to controls (p = <.0001). The DC/TMD diagnosis myalgia, myofascial pain with referral, arthralgia, headache attributed to TMD, disc displacement disorders and degenerative joint disease occurred significantly more often in hEDS compared to controls (p = .000; p = .008; p = .003; p = .000; p = <.0001; p = .010, respectively). No significant differences were found in bite force and in teeth in occlusal contact between the groups (p > .05). On CBCT of the TMJs, subcortical sclerosis occurred significantly more often in hEDS compared to controls (p = .005). CONCLUSION: Symptoms and signs of TMD and osseous changes of the TMJs occurred significantly more often in hEDS. Bite force and teeth in occlusal contact were comparable to controls.

Dysautonomia in hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorders is associated with exercise intolerance and cardiac atrophy.

Dysautonomia is a recognized manifestation in patients with joint hypermobility (JH) disorders. Symptoms can be highly debilitating and commonly include physical deconditioning and poor aerobic fitness. In this study, the prevalence of dysautonomia, range of associated symptoms, patient-reported physical activity levels, and echocardiographic features were assessed retrospectively in a cohort of 144 patients (94% female) with hypermobile Ehlers-Danlos syndrome (hEDS) or hypermobility spectrum disorder (HSD). Echocardiographic parameters of left ventricular size and function were compared between patients with and without dysautonomia as well as to reported values from healthy controls. Dysautonomia was identified in 65% of female and 44% of male subjects and was associated with a high burden of symptomatology, most commonly exercise intolerance (78%). Exercise capacity was limited by dysautonomia, often postural symptoms, in half of all patients. We observed a reduction in physical activity following the onset or significant flare of hEDS/HSD, most strikingly noting the proportion of dysautonomic patients with sedentary lifestyle, which increased from 44% to 85%. JH-related dysautonomia was associated with smaller cardiac chamber sizes, consistent with the previous reports in positional orthostatic tachycardia syndrome. Dysautonomia is prevalent in patients with hEDS/HSD, and exercise intolerance is a key feature and leads to drastic decline in physical activity. Unfavorable cardiac geometry may underlie dysautonomia symptoms and may be due to cardiac atrophy in the setting of aerobic deconditioning.

Endovascular Repair of Postdissection Thoracoabdominal Aortic Aneurysm in Patients With Vascular Ehlers-Danlos Syndrome.

PURPOSE: To report endovascular repair of postdissection thoracoabdominal aortic aneurysm (TAAA) in 2 patients with vascular Ehlers-Danlos syndrome (vEDS). CASE REPORTS: Case 1. A 56-year-old vEDS male patient with a 50-mm type III TAAA [history of aortic root repair, hemiarch replacement, and thoracic endovascular aortic repair (TEVAR) for acute type A aortic dissection (TAAD) 7 years ago] was treated by a 2-stage procedure; first, cervical debranching of the left subclavian artery and second TEVAR and t-branch. The postoperative course was uneventful. Follow-up computed tomography angiography (CTA) 3.5 years postoperatively demonstrated aortic remodeling with patency of targeted visceral vessels and no endoleak. Case 2. A 47-year-old vEDS male patient presented with a TAAA (diameter of 67 mm). The patient had a history of aortic valve and arch replacement with elephant trunk for acute TAAD, and consequently a TEVAR and candy-plug procedure after a ruptured false lumen (FL) aneurysm of the descending thoracic aorta. He also had a surgical repair by an aorto-bi-iliac graft. Two years later, CTA demonstrated aneurysmal FL dilatation distally to the candy-plug and he was treated with fenestrated EVAR (F-EVAR). CONCLUSION: Endovascular repair of postdissection TAAA was feasible and safe with good short-term outcome in 2 patients with vEDS.

Ehlers-Danlos syndrome: what the radiologist needs to know.

Ehlers-Danlos syndrome is a real diagnosis that is erroneously used to explain multiple fractures in suspected child abuse. This paper reviews the clinical and molecular diagnostic criteria for Ehlers-Danlos syndrome. This knowledge can help prevent misdiagnosis and support clinicians when evaluating infants and young children with multiple fractures.

Vascular Ehlers-Danlos syndrome (vEDS): CT and histologic findings of pleural and lung parenchymal damage.

OBJECTIVES: To describe CT features of lung involvement in patients with vascular Ehlers-Danlos syndrome (vEDS), a rare genetic condition caused by pathogenic variants within the COL3A1 gene, characterized by recurrent arterial, digestive, and pulmonary events. MATERIAL AND METHODS: All consecutive vEDS patients referred to the national tertiary referral center for vEDS, between 2004 and 2016, were included. Chest CT scans obtained during the initial vascular work-up were reviewed retrospectively by two chest radiologists for lung involvement. Five surgical samples underwent histologic examination. RESULTS: Among 136 enrolled patients (83 women, 53 men; mean age 37 years) with molecularly confirmed vEDS, 24 (17.6%) had a history of respiratory events: 17 with pneumothorax, 4 with hemothorax, and 3 with hemoptysis that required thoracic surgery in 11. CT scans detected lung parenchymal abnormalities in 78 (57.3%) patients: emphysema (mostly centrilobular and paraseptal) in 44 (32.3%), comparable for smokers and non-smokers; clusters of calcified small pulmonary nodules in 9 (6.6%); and cavitated nodules in 4 (2.9%). Histologic examination of surgical samples found arterial abnormalities, emphysema with alveolar ruptures in 3, accompanied by diffuse hemorrhage and increased hemosiderin resorption. CONCLUSION: In vEDS patients, identification of lung parenchymal abnormalities is common on CT. The most frequently observed CT finding was emphysema suggesting alveolar wall rupture which might facilitate the diagnostic screening of the disease in asymptomatic carriers of a genetic COL3A1 gene mutation. The prognostic value and evolution of these parenchymal abnormalities remain to be evaluated. KEY POINTS: • Patients with vEDS can have lung parenchymal changes on top of or next to thoracal vascular abnormalities and that these changes can be present in asymptomatic cases. • The presence of these parenchymal changes is associated with a slightly higher incidence of respiratory events (although not statistically significant). • Identification of the described CT pattern by radiologists and chest physicians may facilitate diagnostic screening.

Audit of Gastrointestinal Manifestations in Patients with Loeys-Dietz Syndrome and Vascular Ehlers-Danlos Syndrome.

OBJECTIVES: Loeys-Dietz syndrome (LDS) and vascular Ehlers-Danlos Syndrome (vEDS) are genetically heterogeneous heritable disorders of connective tissue. Both are multi-system disorders with dominant vascular pathology and associated gastrointestinal manifestations. AIM: To summarize the abdominal manifestations found in these two disorders in a cohort of patients seen at Mayo Clinic during a period of 25 years. METHODS: Data were collected via the advanced cohort explorer (ACE) of Mayo Clinic records from 1994 to 2018 in patients with vEDS or LDS confirmed by genetic testing and/or medical genetics consultation. We extracted information concerning gastrointestinal symptoms, abdominal hernias, and vascular manifestations or complications. RESULTS: We identified and reviewed records of 68 vEDS and 13 LDS patients. Patients were similar in age at diagnosis and gender distribution. Gastrointestinal symptoms were frequently reported in both disorders and largely similar, although altered bowel function was more prevalent in LDS patients. Hernias were present in similar proportions of patients with vEDS and LDS; however, ventral hernias were more frequent and more likely to be postoperative in vEDS than LDS. LDS patients had more arterial aneurysms overall (76.9% LDS vs. 58% vEDS, p = 0.02) and a higher proportion required arterial repair (69.2% LDS vs. 32.7% vEDS S, p = 0.03). Co-morbidities of autonomic dysfunction, psychopathology (most commonly anxiety, depression, adjustment disorder), and allergy were more prevalent in LDS than vEDS. CONCLUSION: Patients with vEDS and LDS had a propensity for gastrointestinal symptoms, abdominal hernias, and aneurysm formation, but repair for arterial rupture was more prevalent in LDS than EDS.

Republished: Successful treatment of direct carotid-cavernous fistula in a patient with Ehlers-Danlos syndrome type IV without arterial puncture: the transvenous triple-overlay embolization (TAILOREd) technique.

We report successful transvenous treatment of direct carotid-cavernous fistula in a patient with Ehlers-Danlos syndrome type IV using a novel triple-overlay embolization (TAILOREd) technique without the need for arterial puncture, which is known to be highly risky in this patient group. The TAILOREd technique allowed for successful treatment using preoperative MR angiography as a three-dimensional overlay roadmap combined with cone beam CT and live fluoroscopy, precluding the need for an arterial puncture.

A Novel Recurrent COL5A1 Genetic Variant Is Associated With a Dysplasia-Associated Arterial Disease Exhibiting Dissections and Fibromuscular Dysplasia.

OBJECTIVE: While rare variants in the COL5A1 gene have been associated with classical Ehlers-Danlos syndrome and rarely with arterial dissections, recurrent variants in COL5A1 underlying a systemic arteriopathy have not been described. Monogenic forms of multifocal fibromuscular dysplasia (mFMD) have not been previously defined. Approach and Results: We studied 4 independent probands with the COL5A1 pathogenic variant c.1540G>A, p.(Gly514Ser) who presented with arterial aneurysms, dissections, tortuosity, and mFMD affecting multiple arteries. Arterial medial fibroplasia and smooth muscle cell disorganization were confirmed histologically. The COL5A1 c.1540G>A variant is predicted to be pathogenic in silico and absent in gnomAD. The c.1540G>A variant is on a shared 160.1 kb haplotype with 0.4% frequency in Europeans. Furthermore, exome sequencing data from a cohort of 264 individuals with mFMD were examined for COL5A1 variants. In this mFMD cohort, COL5A1 c.1540G>A and 6 additional relatively rare COL5A1 variants predicted to be deleterious in silico were identified and were associated with arterial dissections (P=0.005). CONCLUSIONS: COL5A1 c.1540G>A is the first recurring variant recognized to be associated with arterial dissections and mFMD. This variant presents with a phenotype reminiscent of vascular Ehlers-Danlos syndrome. A shared haplotype among probands supports the existence of a common founder. Relatively rare COL5A1 genetic variants predicted to be deleterious by in silico analysis were identified in ≈2.7% of mFMD cases, and as they were enriched in patients with arterial dissections, may act as disease modifiers. Molecular testing for COL5A1 should be considered in patients with a phenotype overlapping with vascular Ehlers-Danlos syndrome and mFMD.

Bilateral carotid artery dissection due to Eagle syndrome in a patient with vascular Ehlers-Danlos syndrome: a case report.

BACKGROUND: Patients with vascular Ehlers-Danlos syndrome (EDS) occasionally suffer from arterial dissection. Eagle syndrome, which is caused by an elongated styloid process and also causes arterial dissection, is difficult to diagnose and could sometimes be overlooked. Little is known of the coexistence of these two diseases, and treatment strategy is not established. Here, we present a case of bilateral internal carotid artery (ICA) dissection due to Eagle syndrome in a patient with vascular EDS. CASE PRESENTATION: A 30-year-old man was admitted to our hospital because of sudden onset of mild sensory disturbance in his left limbs. He had a history of Ehlers-Danlos syndrome (EDS) and also had left cervical internal carotid artery (ICA) dissection 3 years before. Diffusion-weighted imaging showed acute cerebral infarcts in the right hemisphere. Cervical computed tomography angiography (CTA) revealed the right ICA narrowing at the cervical portion in addition to the previous left cervical ICA dissection. Cervical magnetic resonance imaging (MRI) revealed double-lumen and intramural hematoma at the narrowing portion of the right cervical ICA, which indicates arterial dissection. CT also revealed bilateral elongated styloid processes which are close to each side of cervical ICA. We diagnosed him as bilateral ICA dissection due to bilateral Eagle syndrome. Considering vascular complications due to vascular EDS, we performed closer follow-up with transoral carotid ultrasonography (TOCU). In 4 months, his right ICA dissection gradually improved without stroke recurrence or deterioration of dissection. CONCLUSIONS: Since patients with vascular EDS easily develop arterial dissection, Eagle syndrome may be overlooked. Clinicians should consider Eagle syndrome in the case of vascular EDS with extracranial ICA dissection and close follow-up should be prioritized in cases of Eagle syndrome with vascular EDS.

A review of Ehlers-Danlos syndrome.

Ehlers-Danlos syndrome (EDS) describes a group of heritable disorders of connective tissue comprising mutations in the genes involved in the structure and/or biosynthesis of collagen. Thirteen EDS subtypes are recognized, with a wide degree of symptom overlap among subtypes and with other connective tissue disorders. The clinical hallmarks of EDS are tissue fragility, joint hypermobility, and skin hyperextensibility. Appropriate diagnosis of EDS is important for correct multidisciplinary management and is associated with better clinical outcomes for patients.

The effect of five isometric exercises on glenohumeral translations in healthy subjects and patients with the hypermobility type of the ehlers-danlos syndrome (heds) or hypermobility spectrum disorder (hsd) with multidirectional shoulder instability: an observational study.

OBJECTIVES: To examine whether patients, diagnosed with the hypermobility type of the Ehlers-Danlos syndrome (hEDS) or Hypermobility Spectrum Disorder (HSD), with multidirectional shoulder instability (MDI) have increased humeral head translations compared to healthy controls and to describe the direction of the humeral translations during five exercises. DESIGN: Observational study. SETTING: Ghent University Hospital. PARTICIPANTS: Twenty-seven female patients (aged mean (SD) 35 (13) years) with hEDS/HSD and MDI and 20 female healthy controls (aged 34 (11) years) participated in this study. INTERVENTIONS: The acromiohumeral (AHD) and humeralglenoid distance (HGD) were measured using ultrasound during five isometric exercises: shoulder external rotation, shoulder extension, shoulder flexion, elbow extension and holding a 2kg dumbbell. MAIN OUTCOME MEASURES: Ultrasound measures of the AHD and HGD. RESULTS: During isometric shoulder extension, elbow extension and dumbbell loading, patients had a significantly larger change in AHD compared to controls. In patients, the AHD was significantly smaller during isometric shoulder flexion, extension and elbow extension compared to the AHD measured in rest. By contrast, the AHD was significantly larger during isometric external rotation and dumbbell loading compared to the AHD measured in rest. Regarding the HGD, no significant differences between patients and controls were observed. However, significantly smaller HGD values were found in patients during isometric shoulder flexion compared to the HGD in rest. CONCLUSIONS: Isometric external rotation and holding a 2kg dumbbell caused an inferior translation in patients with hEDS/HSD and MDI, whereas isometric shoulder flexion and shoulder/elbow extension respectively led to an anterior-superior and superior translation.

Síndrome de Ehlers-Danlos clásico: hallazgos clínicos y ecográficos / Classic Ehlers-Danlos Syndrome: Clinical and Ultrasound Findings

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A family with Classical Ehlers-Danlos Syndrome (cEDS), mild bone fragility and without vascular complications, caused by the p.Arg312Cys mutation in COL1A1.

The Ehlers-Danlos syndromes (EDS) are heritable disorders of connective tissue (HDCT) with joint hypermobility, skin hyperextensibility and tissue fragility, which were recently re-classified (2017 International Classification). Most patients (>90%) with Classical Ehlers-Danlos syndrome (cEDS) have a mutation in the COL5A1 or COL5A2 genes encoding type V procollagen. A small number of patients with the p.Arg312Cys mutation in COL1A1 have been reported with overlapping features of both cEDS and vascular EDS (vEDS). In this report, we describe two patients from a large family with this mutation and clinical features consistent with cEDS without vascular complications. The proband presented with congenital hip dislocation (previously reported in one patient), the mother of the proband with multiple fractures in childhood, and dental defects (novel findings). The small number of patients reported with this mutation and proportion with vascular complications suggests that vascular surveillance should still be recommended.

Current and Emerging Imaging Techniques in Patients with Genetic Aortic Syndromes. / Aktuelle Bildgebungs-Strategien bei genetisch bedingten Erkrankungen der Aorta.

BACKGROUND: Patients with genetic aortic syndromes such as Marfan or Loeys-Dietz syndrome have a decreased life expectancy due to the risk of aortic dissection and rupture. Imaging plays an important role in the acute setting but also in the initial diagnosis and image-based monitoring. In this article, we provide an overview of the most common genetic aortic syndromes and recommended imaging strategies. Furthermore, we highlight modern imaging methods allowing for the quantification of hemodynamic changes in aortic disease. METHOD: This is a narrative review article on genetic aortic syndromes and recommended imaging strategies, where we take into account expert opinions and standard-of-care practices from our own center. RESULTS AND CONCLUSION: Radiological imaging plays a key role in the initial diagnosis and surveillance of patients with genetic aortic syndromes. Radiologists contribute significantly to the multi-disciplinary setting of genetic aortic syndromes with knowledge of special features and recommended imaging methods. Accurate measurement of the aorta is crucial, particularly in terms of diameter-based surgical treatment algorithms. Modern imaging methods like 4D-flow MRI and pulse wave velocity have a potential to further improve individualized risk stratification in patients with genetic aortic syndromes. KEY POINTS: · The risk for cardiovascular complications such as acute aortic syndrome is increased in patients with genetic aortic syndromes.. · Recommended time intervals between image-based monitoring depend on the underlying aortic disease.. · CT-angiography should be used only in the acute setting.. · Non-contrast MR-angiography is adequate for screening and image-based monitoring of patients with genetic aortic syndromes.. CITATION FORMAT: · Weinrich JM, Lenz A, Girdauskas E et al. Current and Emerging Imaging Techniques in Patients with Genetic Aortic Syndromes. Fortschr Röntgenstr 2020; 192: 50 - 58.