Diagnosis of vascular Ehlers-Danlos syndrome in Italy: Clinical findings and novel COL3A1 mutations

AbstractEhlers–Danlos syndrome (EDS) is a genetic disease leading to abnormalities in mechanical properties of different tissues. Here we quantify corneal biomechanical properties in an adult classic EDS mouse model using two different measurement approaches suited for murine corneal mechanical characterization and relate differences to stromal structure using Second Harmonic Generation (SHG) microscopy. Quasi-static Optical Coherence Elastography (OCE) was conducted non-invasively during ambient pressure modulation by − 3 mmHg. 2D-extensometry measurements was conducted invasively consisting of a pre-conditioning cycle, a stress-relaxation test and a rupture test. In a total of 28 eyes from a Col5a1+/− mouse model and wild-type C57BL/6 littermates (wt), Col5a1+/− corneas were thinner when compared to wt, (125 ± 11 vs 148 ± 10 μm, respectively, p < 0.001). Short-term elastic modulus was significantly increased in OCE (506 ± 88 vs 430 ± 103 kPa, p = 0.023), and the same trend was observed in 2D-extensometry (30.7 ± 12.1 kPa vs 21.5 ± 5.7, p = 0.057). In contrast, in stress relaxation tests, Col5a1+/− corneas experienced a stronger relaxation (55% vs 50%, p = 0.01). SHG microscopy showed differences in forward and backward scattered signal indicating abnormal collagen fibrils in Col5a1+/− corneas. We propose that disturbed collagen fibril structure in Col5a1+/− corneas affects the viscoelastic properties. Results presented here support clinical findings, in which thin corneas with global ultrastructural alterations maintain a normal corneal shape.

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REHABILITASI MEDIK PADA SINDROM EHLERS-DANLOS

JURNAL BIOMEDIK (JBM) ◽

10.35790/jbm.6.2.2014.5549 ◽

2014 ◽

Vol 6 (2) ◽

Author(s):

Ivan A. Chandra ◽

Engeline Angliadi

Keyword(s):

Daily Living ◽

Weight Bearing ◽

Joint Hypermobility ◽

Clinical Findings ◽

Joint Stability ◽

Connective Tissue Disorders ◽

Ehlers Danlos Syndrome ◽

Dna Test ◽

Comprehensive Rehabilitation ◽

Danlos Syndrome

Abstract: Ehlers-Danlos syndrome is a group of inherited connective tissue disorders that manifests as hypermobility joint, hyperextensibility of the skin, and tissue fragility. There are 6 variants of this syndrome as follows: hypermobility, classic, vascular, kyphoscoliosis, athroclasia, and dermatosparaxis. The clinical manifestation of Ehlers-Danlos syndrome is often related to joint and skin. However, it rarely manifests as fragility or rupture of artery, scoliosis, and mitral valve disorder. The diagnosis of Ehlers-Danlos syndrome is based on clinical findings, family history with this syndrome, and additional tests inter alia DNA test. The management of Ehlers-Danlos syndrome could be medication, surgery, and rehabilitation. This rehabilitation is focused on increasing the joint stability, prohibiting for excessive burden to weight bearing joints, and using modified device to support activites of daily living without worsening the symptoms as well as supporting the psychological and medical social aspects of the patient. Keywords: Ehlers-Danlos syndrome, joint hypermobility, comprehensive rehabilitation Abstrak: Sindrom Ehlers-Danlos (SED) adalah sekelompok gangguan pada jaringan penyambung yang bersifat diturunkan dan bermanifestasi sebagai hipermobilitas sendi, hiperekstensibilitas kulit, dan kerapuhan jaringan. Terdapat 6 jenis SED yaitu: hipermobilitas, klasik, vaskuler, kifoskoliosis, artrokalasia, dan dermatosparaksis. Manifestasi klinis SED sering berkaitan dengan sendi dan kulit. Manifestasi lain yang lebih jarang ditemukan antara lain kerapuhan atau ruptur pembuluh darah arteri, skoliosis, serta gangguan katup mitral. Diagnosis SED ditegakkan berdasarkan penemuan klinis, riwayat keluarga dengan SED, serta pemeriksaan penunjang antara lain tes DNA. Penanganan SED terdiri dari medikasi, operasi, dan rehabilitasi. Penanganan rehabilitasi difokuskan pada peningkatan stabilitas sendi, pencegahan beban berlebih pada sendi yang weight bearing, serta penggunaan modifikasi alat untuk membantu aktifitas sehari-hari tanpa memperberat gejala. Selain itu, rehabilitasi medik juga berperan penting terhadap aspek psikologik maupun sosial medik pasien SED. Kata kunci: sindroma Ehlers-Danlos, hipermobilitas sendi, rehabilitasi komprehensif

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Erratum to “Letter to the Editor – Diagnosis of vascular Ehlers-Danlos syndrome in Italy: Clinical findings and novel COL3A1 mutations” [J. Dermatol. Sci. 64 (2011) 237–248]

Journal of Dermatological Science ◽

10.1016/j.jdermsci.2011.11.008 ◽

2012 ◽

Vol 65 (1) ◽

pp. 77 ◽

Cited By ~ 1

Author(s):

Bruno Drera ◽

Nicoletta Zoppi ◽

Marco Ritelli ◽

Gianluca Tadini ◽

Marina Venturini ◽

...

Keyword(s):

Clinical Findings ◽

Ehlers Danlos Syndrome ◽

Letter To The Editor ◽

Danlos Syndrome

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Aortic Disease in the Young: Genetic Aneurysm Syndromes, Connective Tissue Disorders, and Familial Aortic Aneurysms and Dissections

International Journal of Vascular Medicine ◽

10.1155/2013/267215 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 15

Author(s):

Marcelo Cury ◽

Fernanda Zeidan ◽

Armando C. Lobato

Keyword(s):

Aortic Disease ◽

Clinical Findings ◽

Aortic Aneurysms ◽

Genetic Syndromes ◽

Ehlers Danlos Syndrome ◽

Thoracic Aortic Aneurysms ◽

Abdominal Aortic ◽

Autosomal Dominant Polycystic Kidney ◽

Thoracic And Abdominal ◽

Danlos Syndrome

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.

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Expanding the Clinical and Mutational Spectrum of Recessive AEBP1-Related Classical-Like Ehlers-Danlos Syndrome

Genes ◽

10.3390/genes10020135 ◽

2019 ◽

Vol 10 (2) ◽

pp. 135 ◽

Cited By ~ 7

Author(s):

Marco Ritelli ◽

Valeria Cinquina ◽

Marina Venturini ◽

Letizia Pezzaioli ◽

Anna Formenti ◽

...

Keyword(s):

Missense Variant ◽

Causal Variant ◽

Joint Hypermobility ◽

Clinical Findings ◽

Ehlers Danlos Syndrome ◽

Pathogenic Variants ◽

Fibrillar Collagens ◽

Atrophic Scars ◽

Minor Criteria ◽

Danlos Syndrome

Ehlers-Danlos syndrome (EDS) comprises clinically heterogeneous connective tissue disorders with diverse molecular etiologies. The 2017 International Classification for EDS recognized 13 distinct subtypes caused by pathogenic variants in 19 genes mainly encoding fibrillar collagens and collagen-modifying or processing proteins. Recently, a new EDS subtype, i.e., classical-like EDS type 2, was defined after the identification, in six patients with clinical findings reminiscent of EDS, of recessive alterations in AEBP1, which encodes the aortic carboxypeptidase–like protein associating with collagens in the extracellular matrix. Herein, we report on a 53-year-old patient, born from healthy second-cousins, who fitted the diagnostic criteria for classical EDS (cEDS) for the presence of hyperextensible skin with multiple atrophic scars, generalized joint hypermobility, and other minor criteria. Molecular analyses of cEDS genes did not identify any causal variant. Therefore, AEBP1 sequencing was performed that revealed homozygosity for the rare c.1925T>C p.(Leu642Pro) variant classified as likely pathogenetic (class 4) according to the American College of Medical Genetics and Genomics (ACMG) guidelines. The comparison of the patient’s features with those of the other patients reported up to now and the identification of the first missense variant likely associated with the condition offer future perspectives for EDS nosology and research in this field.

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