scholarly journals Az Ehlers–Danlos-szindrómák korszerű osztályozása és multidiszciplináris tünettana

2019 ◽  
Vol 160 (16) ◽  
pp. 603-612
Author(s):  
Fanni Virág Ralovich ◽  
Norbert Kiss ◽  
Krisztina Horváth ◽  
Sarolta Kárpáti ◽  
Márta Medvecz
Keyword(s):  
Clinical Care ◽  
Joint Hypermobility ◽  
Point Of View ◽  
Clinical Aspects ◽  
The Novel ◽  
Ehlers Danlos Syndrome ◽  
Large Populations ◽  
Leading Symptom ◽  
Danlos Syndrome

Abstract: In this review article, the authors summarize the clinical aspects of the novel classification of Ehlers–Danlos syndrome, which is a group of rare, hereditary connective tissue disorders. The leading symptom of the Ehlers–Danlos syndrome group is joint hypermobility, skin hyperextensibility and generalized tissue fragility. Ehlers–Danlos syndrome displays a high clinical and genetic heterogeneity and harbors many multidisciplinary properties. Certain subtypes only affect the quality of life, while other forms may lead to severe, even fatal vascular or intestinal complications. Last year, based on the data of various international genotype-phenotype correlation studies of large populations, a new classification of the syndrome’s clinical subtypes was introduced. The novel international nosology of Ehlers–Danlos syndromes published in 2017 delineates 13 clinical subtypes, describes their genetic background and defines major and minor diagnostic criteria for each subtype. We gathered the complex, multidisciplinary symptoms of Ehlers–Danlos syndromes in a table to assist the diagnosis from a differential diagnostic point of view. In the clinical practice, the proper diagnosis of patients affected by the Ehlers–Danlos syndrome group is essential to give optimal clinical care and to prevent the development of severe complications. Orv Hetil. 2019; 160(16): 603–612.

scholarly journals Novel TNXB Variants in Two Italian Patients with Classical-Like Ehlers-Danlos Syndrome

Genes ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 967 ◽  
Author(s):  
Lucia Micale ◽  
Vito Guarnieri ◽  
Bartolomeo Augello ◽  
Orazio Palumbo ◽  
Emanuele Agolini ◽  
...  
Keyword(s):  
Complex Structure ◽  
Joint Hypermobility ◽  
Null Alleles ◽  
Molecular Testing ◽  
The Novel ◽  
Ehlers Danlos Syndrome ◽  
Novel Variants ◽  
Brachial Vein ◽  
Italian Women ◽  
Danlos Syndrome

TNXB-related classical-like Ehlers-Danlos syndrome (TNXB-clEDS) is an ultrarare type of Ehlers-Danlos syndrome due to biallelic null variants in TNXB, encoding tenascin-X. Less than 30 individuals have been reported to date, mostly of Dutch origin and showing a phenotype resembling classical Ehlers-Danlos syndrome without atrophic scarring. TNXB-clEDS is likely underdiagnosed due to the complex structure of the TNXB locus, a fact that complicates diagnostic molecular testing. Here, we report two unrelated Italian women with TNXB-clEDS due to compound heterozygosity for null alleles in TNXB. Both presented soft and hyperextensible skin, generalized joint hypermobility and related musculoskeletal complications, and chronic constipation. In addition, individual 1 showed progressive finger contractures and shortened metatarsals, while individual 2 manifested recurrent subconjunctival hemorrhages and an event of spontaneous rupture of the brachial vein. Molecular testing found the two previously unreported c.8278C > T p.(Gln2760*) and the c.(2358 + 1_2359 − 1)_(2779 + 1_2780 − 1)del variants in Individual 1, and the novel c.1150dupG p.(Glu384Glyfs*57) and the recurrent c.11435_11524+30del variants in Individual 2. mRNA analysis confirmed that the c.(2358 + 1_2359 − 1)_(2779 + 1_2780 − 1)del variant causes a frameshift leading to a predicted truncated protein [p.(Thr787Glyfs*40)]. This study refines the phenotype recently delineated in association with biallelic null alleles in TNXB, and adds three novel variants to its mutational repertoire. Unusual digital anomalies seem confirmed as possibly peculiar of TNXB-clEDS, while vascular fragility could be more than a chance association also in this Ehlers-Danlos syndrome type.

scholarly journals Gonosomal Mosaicism for a Novel COL5A1 Pathogenic Variant in Classic Ehlers-Danlos Syndrome

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1928
Author(s):  
Lucia Micale ◽  
Thomas Foiadelli ◽  
Federica Russo ◽  
Luigia Cinque ◽  
Francesco Bassanese ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Sanger Sequencing ◽  
Digital Pcr ◽  
Connective Tissue Disorder ◽  
Joint Hypermobility ◽  
The Novel ◽  
Ehlers Danlos Syndrome ◽  
Targeted Ngs ◽  
Next Generation Sequencing Ngs ◽  
Danlos Syndrome

(1) Background: Classic Ehlers-Danlos syndrome (cEDS) is a heritable connective tissue disorder characterized by joint hypermobility and skin hyperextensibility with atrophic scarring. Many cEDS individuals carry variants in either the COL5A1 or COL5A2 genes. Mosaicism is relatively common in heritable connective tissue disorders but is rare in EDS. In cEDS, a single example of presumed gonosomal mosaicism for a COL5A1 variant has been published to date. (2) Methods: An 8-year-old girl with cEDS was analyzed by next-generation sequencing (NGS). Segregation was performed by Sanger sequencing in her unaffected parents. In the father, the mosaicism of the variant was further analyzed by targeted NGS and droplet digital PCR (ddPCR) in the blood and by Sanger sequencing in other tissues. (3) Results: The NGS analysis revealed the novel germline heterozygous COL5A1 c.1369G>T, p.(Glu457*) variant in the proband. Sanger chromatogram of the father’s blood specimen suggested the presence of a low-level mosaicism for the COL5A1 variant, which was confirmed by NGS and estimated to be 4.8% by ddPCR. The mosaicism was also confirmed by Sanger sequencing in the father’s saliva, hair bulbs and nails. (4) Conclusions: We described the second case of cEDS caused by paternal gonosomal mosaicism in COL5A1. Parental mosaicism could be an issue in cEDS and, therefore, considered for appropriate genetic counseling.

scholarly journals The first case report of Kyphoscoliotic Ehlers-Danlos syndrome of chinese origin with a novel PLOD1 gene mutation

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaolin Ni ◽  
Chenxi Jin ◽  
Yan Jiang ◽  
Ou Wang ◽  
Mei Li ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Clinical Manifestations ◽  
Joint Hypermobility ◽  
Minor Trauma ◽  
X Rays ◽  
Ehlers Danlos Syndrome ◽  
Chinese Origin ◽  
First Case ◽  
Blue Sclerae ◽  
Danlos Syndrome

Abstract Background Kyphoscoliotic Ehlers-Danlos syndrome (kEDS) is a rare autosomal recessive connective tissue disorder characterized by progressive kyphoscoliosis, congenital muscular hypotonia, marked joint hypermobility, and severe skin hyperextensibility and fragility. Deficiency of lysyl hydroxylase 1 (LH1) due to mutations of PLOD1 (procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1) gene has been identified as the pathogenic cause of kEDS (kEDS-PLOD1). Up to now, kEDS-PLOD1 has not been reported among Chinese population. Case presentation A 17-year-old Chinese male patient presenting with hypotonia, joint hypermobility and scoliosis was referred to our hospital. After birth, he was found to have severe hypotonia leading to delayed motor development. Subsequently, joint hypermobility, kyphoscoliosis and amblyopia were found. Inguinal hernia was found at age 5 years and closed by surgery. At the same time, he presented with hyperextensible and bruisable velvety skin with widened atrophic scarring after minor trauma. Dislocation of elbow joint was noted at age of 6 years. Orthopedic surgery for correction of kyphoscoliosis was performed at age 10 years. His family history was unremarkable. Physical examination revealed elevated blood pressure. Slight facial dysmorphologies including high palate, epicanthal folds, and down-slanting palpebral fissures were found. He also had blue sclerae with normal hearing. X-rays revealed severe degree of scoliosis and osteopenia. The Echocardiography findings were normal. Laboratory examination revealed a slightly elevated bone turnover. Based on the clinical manifestations presented by our patient, kEDS was suspected. Genetic analysis revealed a novel homozygous missense mutation of PLOD1 (c.1697 G > A, p.C566Y), confirming the diagnosis of kEDS-PLOD1. The patient was treated with alfacalcidol and nifedipine. Improved physical strength and normal blood pressure were reported after 12-month follow-up. Conclusions This is the first case of kEDS-PLOD1 of Chinese origin. We identified one novel mutation of PLOD1, extending the mutation spectrum of PLOD1. Diagnosis of kEDS-PLOD1 should be considered in patients with congenital hypotonia, progressive kyphoscoliosis, joint hypermobility, and skin hyperextensibility and confirmed by mutation analysis of PLOD1.

scholarly journals Ehlers-Danlos syndrome presenting with primary nocturnal enuresis

2020 ◽  
Vol 13 (2) ◽  
pp. e231977
Author(s):  
Margarida Cunha ◽  
Mafalda Matias ◽  
Inês Marques
Keyword(s):  
Genetic Testing ◽  
Nocturnal Enuresis ◽  
Bladder Dysfunction ◽  
Connective Tissue Disorder ◽  
Joint Hypermobility ◽  
Urinary Urgency ◽  
Beighton Score ◽  
Ehlers Danlos Syndrome ◽  
Primary Nocturnal Enuresis ◽  
Danlos Syndrome

Ehlers-Danlos syndrome (EDS), hypermobility type, is probably the most common EDS type, as well as the most common heritable connective tissue disorder. Bladder dysfunction is a rare clinical manifestation of EDS and manifests itself as primary nocturnal enuresis. We present a 10-year-old boy referred to the paediatrics nephrology consultation due to primary nocturnal enuresis and day time symptoms of urinary urgency. During the appointment, a tendency to joint hypermobility was noted. On evaluation the skin was hyperextensible and the Beighton score was positive. The genetic testing revealed a variant of the COL5A1 gene not yet described in the literature.

scholarly journals Increased augmentation index in patients with Ehlers-Danlos syndrome

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Maurice Roeder ◽  
Sira Thiel ◽  
Frederic Baumann ◽  
Noriane A. Sievi ◽  
Marianne Rohrbach ◽  
...  
Keyword(s):  
Arterial Stiffness ◽  
Augmentation Index ◽  
Positive Association ◽  
Joint Hypermobility ◽  
Applanation Tonometry ◽  
Classical Type ◽  
Healthy Controls ◽  
Ehlers Danlos Syndrome ◽  
Vascular Type ◽  
Danlos Syndrome

Abstract Background Ehlers-Danlos Syndrome (EDS) comprises a heterogeneous group of diseases characterized by joint hypermobility, connective tissue friability, and vascular fragility. Reliable prognostic factors predicting vascular disease progression (e.g. arterial aneurysms, dissections, and ruptures) in EDS patients are still missing. Recently, applanation tonometry derived augmentation index (AIx), an indirect marker of arterial stiffness, has shown to be positively associated with progression of aortic disease in Marfan syndrome. In this study, we assessed aortic AIx in patients with EDS and matched healthy controls. Methods We performed noninvasive applanation tonometry in 61 adults with EDS (43 women and 18 men aged 39.3 ± 14.6 years) and 61 age-, gender-, height-, and weight-matched healthy controls. Radial artery pulse waveforms were recorded and analyzed using the SphygmoCor System (AtCor Medical, Sydney, NSW, Australia). Calculated AIx was adjusted to a heart rate of 75/min. Groups were compared and association between AIx and EDS was determined by univariate and multivariate regression analysis. Results EDS patients were categorized in classical type EDS (34%), hypermobile type EDS (43%), vascular type EDS (5%), or remained unassignable (18%) due to overlapping features. EDS patients showed a significantly increased aortic AIx compared to healthy controls (22.8% ± 10.1 vs 14.8% ± 14.0, p < 0.001). EDS showed a positive association with AIx; independent of age, sex, height, blood pressure, medication, and pack years of smoking. Conclusions Patients with EDS showed elevated AIx, indicating increased arterial stiffness when compared to healthy controls. Further investigations are needed in order to assess the prognostic value of increased AIx for cardiovascular outcomes in patients with EDS.

Low tendon stiffness and abnormal ultrastructure distinguish classic Ehlers‐Danlos syndrome from benign joint hypermobility syndrome in patients

2014 ◽  
Vol 28 (11) ◽  
pp. 4668-4676 ◽  
Author(s):  
Rie Harboe Nielsen ◽  
Christian Couppé ◽  
Jacob Kildevang Jensen ◽  
Morten Raun Olsen ◽  
Katja Maria Heinemeier ◽  
...  
Keyword(s):  
Joint Hypermobility ◽  
Hypermobility Syndrome ◽  
Joint Hypermobility Syndrome ◽  
Ehlers Danlos Syndrome ◽  
Tendon Stiffness ◽  
Benign Joint Hypermobility Syndrome ◽  
Danlos Syndrome

scholarly journals Dermal Ultrastructure in Low Beighton Score Members of 17 Families with Hypermobile-Type Ehlers-Danlos Syndrome

2012 ◽  
Vol 2012 ◽  
pp. 1-3 ◽  
Author(s):  
Trinh Hermanns-Lê ◽  
Marie-Annick Reginster ◽  
Claudine Piérard-Franchimont ◽  
Philippe Delvenne ◽  
Gérald E. Piérard ◽  
...  
Keyword(s):  
Clinical Parameter ◽  
Joint Hypermobility ◽  
Elastic Fibers ◽  
Hypermobility Syndrome ◽  
Beighton Score ◽  
Joint Hypermobility Syndrome ◽  
Ehlers Danlos Syndrome ◽  
Transmission Electron ◽  
Asymptomatic Subjects ◽  
Danlos Syndrome

The distinction between the Ehlers-Danlos syndrome hypermobile type (EDSH) and the benign joint hypermobility syndrome (BJHS) is unclear. The aim of the present study was to compare skin ultrastructural abnormalities of EDSH and BJHS among different families. Skin of 23 EDSH, 27 BJHS, and 41 asymptomatic subjects from 17 families was examined using transmission electron microscopy. Similar ultrastructural abnormalities were found irrespective of the Beighton score. Flower-like collagen fibrils represented the key change and elastic fibers were altered as well. Beighton score is a clinical parameter rating joint mobility that appeared unrelated to quantitative and qualitative collagen ultrastructural alterations in the skin. Some EDSH family members fit with BJHS diagnosis. BJHS possibly represents a mild variant of EDSH.

Sign in / Sign up

Export Citation Format

Share Document