scholarly journals Identification of the novel COL5A1 c.3369_3431dup, p.(Glu1124_Gly1144dup) variant in a patient with incomplete classical Ehlers–Danlos syndrome: The importance of phenotype‐guided genetic testing

2020 ◽  
Vol 8 (10) ◽  
Author(s):  
Marco Ritelli ◽  
Valeria Cinquina ◽  
Marina Venturini ◽  
Marina Colombi
Keyword(s):  
Genetic Testing ◽  
The Novel ◽  
Ehlers Danlos Syndrome ◽  
Danlos Syndrome

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 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 Twin pregnancy with untyped Ehlers-Danlos syndrome requiring prompt genetic testing: A case report

2022 ◽  
pp. e00384
Author(s):  
Shiori Ogawa ◽  
Tasuku Mariya ◽  
Yuya Fujibe ◽  
Marie Ogawa ◽  
Keiko Ikeda ◽  
...  
Keyword(s):  
Case Report ◽  
Genetic Testing ◽  
Twin Pregnancy ◽  
Ehlers Danlos Syndrome ◽  
Danlos Syndrome

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 Accuracy of Clinical Diagnostic Criteria for Patients With Vascular Ehlers-Danlos Syndrome in a Tertiary Referral Centre

2019 ◽  
Vol 12 (3) ◽  
Author(s):  
Pierrick Henneton ◽  
Juliette Albuisson ◽  
Salma Adham ◽  
Anne Legrand ◽  
Jean Michael Mazzella ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Diagnostic Accuracy ◽  
Negative Predictive Value ◽  
Diagnostic Criteria ◽  
Predictive Value ◽  
Odds Ratio ◽  
Diagnostic Odds Ratio ◽  
Tertiary Referral ◽  
Ehlers Danlos Syndrome ◽  
Danlos Syndrome

Background: Vascular Ehlers-Danlos syndrome is a rare inherited connective tissue disease secondary to mutations within the COL3A1 gene. The diagnosis of vascular Ehlers-Danlos syndrome is challenging, and patient selection for genetic testing relies on diagnostic criteria, which have never been evaluated. Methods: All patients seen at a dedicated tertiary referral center for a suspicion of vascular Ehlers-Danlos syndrome between January 2001 and March 2016 were retrospectively included in a diagnostic accuracy study. Major and minor diagnostic criteria of the Villefranche classification were tested for sensitivity, specificity, positive and negative predictive values, according to results of genetic testing. Results: N=519 patients were eligible for analysis dividing into n=384 probands and n=135 relatives. A pathogenic COL3A1 variant was identified in n=165 (31.8%) patients. The Villefranche criteria were met for n=248 patients with a sensitivity of 79% (95% CI, 0.72–0.85) and a negative predictive value of 87% (95% CI, 0.83–0.91). Diagnostic accuracy was highest for symptomatic probands (sensitivity 92%; negative predictive value 95%) with limited specificity (60%). Probands ≤25 years had the worst diagnostic performance. The revised diagnostic Criteria (2017) were less accurate than the Villefranche classification (overall diagnostic odds-ratio, 4.17 versus 7.8; probands diagnostic odds-ratio, 4.04 versus 18.1; and probands ≤25 years diagnostic odds-ratio, 2.36 versus 5.1) mainly due to a lack of sensitivity. Conclusions: The Villefranche criteria provide accurate detection of symptomatic probands in specialized practice but have limited specificity. The revised diagnostic criteria for vascular Ehlers-Danlos syndrome have increased specificity, but its overall performance is poorer. The early clinical diagnosis of probands without family history is not addressed by both diagnostic classifications.

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 Spontaneous Coronary Artery Dissection as Presenting Feature of Vascular Ehlers-Danlos Syndrome

2021 ◽  
Vol 11 (3) ◽  
pp. 129-131
Author(s):  
J. Bos ◽  
E. Overwater ◽  
M.T. Dirksen ◽  
S. Simsek ◽  
S. Demirdas ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Chest Pain ◽  
Coronary Artery ◽  
Sudden Onset ◽  
Artery Dissection ◽  
Spontaneous Coronary Artery Dissection ◽  
Coronary Artery Dissection ◽  
Ehlers Danlos Syndrome ◽  
Danlos Syndrome

A spontaneous coronary artery dissection as the sole presenting feature of vascular Ehlers-Danlos syndrome is an uncommon finding. We present a 33-year-old woman with sudden onset chest pain caused by a spontaneous coronary artery dissection. Genetic testing revealed vascular Ehlers-Danlos syndrome as the underlying cause. Specifically, we show the value of genetic testing, which in some patients may be the only way of establishing a diagnosis.

Ehlers-Danlos Syndrome, Kyphoscoliotic Type (Formerly Type VI) as Differential Diagnosis to Neuromuscular Diseases

2016 ◽  
Vol 47 (S 01) ◽  
Author(s):  
M. Schroth ◽  
C. Reihle ◽  
M. Wachowsky ◽  
L. Travan ◽  
M. Buob ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Neuromuscular Diseases ◽  
Ehlers Danlos Syndrome ◽  
Danlos Syndrome
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