scholarly journals A Heterozygous Missense Variant in the COL5A2 in Holstein Cattle Resembling the Classical Ehlers–Danlos Syndrome

Animals ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 2002
Author(s):  
Joana G. P. Jacinto ◽  
Irene M. Häfliger ◽  
Inês M. B. Veiga ◽  
Anna Letko ◽  
Cinzia Benazzi ◽  
...  
Keyword(s):  
Clinical Investigation ◽  
Missense Variant ◽  
Causal Variant ◽  
Connective Tissue Disorder ◽  
Joint Hypermobility ◽  
Large Animal Model ◽  
Large Animal ◽  
Ehlers Danlos Syndrome ◽  
Skin Fragility ◽  
Danlos Syndrome

Classical Ehlers–Danlos syndrome (cEDS) is a heritable connective tissue disorder characterized by variable degrees of skin hyperextensibility and fragility, atrophic scarring, and generalized joint hypermobility. The purpose of this study was to characterize the clinicopathological phenotype of a cEDS-affected Holstein calf and to identify the causative genetic variant associated with the disorder by whole-genome sequencing (WGS). A 3-day-old female Holstein calf was referred because of easily induced skin detachment and hyperextensibility in the neck. A complete clinical investigation was performed in the calf, dam, and maternal-grandmother. The calf and dam showed hyperextensibility of the neck skin and atrophic scarring; additionally, the calf presented skin fragility. Moreover, the histopathology of biopsies from the calf and its dam showed that the collagen bundles in affected skin areas were wavy, short, thin, and surrounded by edema and moderate to severe acute hemorrhages. Genetic analysis revealed a private heterozygous missense variant in COL5A2 (c.2366G>T; p.Gly789Val) that was present only in the calf and dam. This confirmed the diagnosis of cEDS and represents the first report of a causal variant for cEDS in cattle and the first COL5A2-related large animal model.

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

Genes ◽  
2019 ◽  
Vol 10 (2) ◽  
pp. 135 ◽  
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.

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 Considerations for lactation with Ehlers-Danlos syndrome: a narrative review

2022 ◽  
Vol 17 (1) ◽  
Author(s):  
Jimi Francis ◽  
Darby D. Dickton
Keyword(s):  
Connective Tissue ◽  
Human Milk ◽  
Joint Hypermobility ◽  
Narrative Review ◽  
Diagnostic Methods ◽  
Care Providers ◽  
Ehlers Danlos Syndrome ◽  
Lack Of Information ◽  
Skin Fragility ◽  
Danlos Syndrome

Abstract Background Ehlers-Danlos syndrome (EDS) is a rare genetic connective tissue condition that is poorly understood in relation to lactation. As diagnostic methods improve, prevalence has increased. EDS, a disorder that impacts connective tissue, is characterized by skin extensibility, joint hypermobility, and fragile tissue which can affect every organ and body system leading to complications during pregnancy, delivery, and the postpartum period. Traits of this disease can cause mild to severe physiologic and functional obstacles during lactation. Unfortunately, there is little clinical evidence and minimal guidance for lactation management, and providers may feel uncomfortable and hesitant to address these concerns with patients due to a lack of readily available resources on the subject and inexperience with such patients. This narrative review describes and discusses the types of EDS, identifying symptoms, considerations, and precautions for care providers to implement during lactation and breastfeeding. Methods An electronic search of relevant citations was conducted using the databases Cochrane, PubMed, and Google Scholar from 1 January 2000 to 1 November 2021. Search terms used were Ehlers-Danlos syndrome, Hypermobility Syndrome, breastfeeding, lactation, breastmilk expression, breastmilk collection, human milk expression, human milk collection, and infant feeding. The search of these databases yielded zero results. As no research articles on EDS were directly related to lactation, this narrative review includes articles found that related to the health of mothers relevant to maternal function during lactation. Discussion For the healthcare provider, identifying characteristics of EDS can improve the management of lactation challenges. Mothers may experience generalized symptoms from gastrointestinal distress to fatigue or chronic pain, while they also may suffer from more specific joint complaints and injuries, such as dislocations / subluxations, or skin fragility. Such obstacles can generate impediments to breastfeeding and create unique challenges for breastfeeding mothers with EDS. Unfortunately, new mothers with these symptoms may have them overlooked or not addressed, impacting a mother’s ability to meet her breastfeeding intentions. While there are some published research manuscripts on EDS and pregnancy, there is a lack of information regarding breastfeeding and lactation. Additional research is needed to help guide EDS mothers to achieve their breastfeeding intentions.

scholarly journals Carpometacarpal Arthroplasty and Ulnar Collateral Ligament Reconstruction in a Patient with Suspected Ehlers-Danlos Syndrome: A Case Report and Review of the Literature

2019 ◽  
Vol 12 (S 01) ◽  
pp. S64-S66
Author(s):  
Scott Samona ◽  
Michelle Palazzo
Keyword(s):  
Ligament Reconstruction ◽  
Ulnar Collateral Ligament ◽  
Metacarpophalangeal Joint ◽  
Connective Tissue Disorder ◽  
Joint Hypermobility ◽  
Collateral Ligament ◽  
Ehlers Danlos Syndrome ◽  
History Of ◽  
Thumb Carpometacarpal ◽  
Danlos Syndrome

AbstractEhlers-Danlos syndrome (EDS) is a disorder that presents with a heterogeneous constellation of symptoms, ranging from clinically silent to rapidly deteriorating. It is a multisystemic connective tissue disorder that may result in any number of manifestations, with joint hypermobility being a classic manifestation. We present a case of a 58-year-old woman, with suspected EDS, who presented with several years’ history of bilateral thumb pain, with imaging and physical examination findings consistent with bilateral thumb carpometacarpal (CMC) arthritis with metacarpophalangeal joint (MPJ) hypermobility. The Beighton hypermobility score was consistent with suspected EDS. Our patient underwent thumb CMC arthroplasty with ulnar collateral ligament (UCL) reconstruction.

scholarly journals Report of two siblings with spondylodysplastic Ehlers-Danlos syndrome and B4GALT7 deficiency

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Delia Lorenz ◽  
Wolfram Kress ◽  
Ann-Kathrin Zaum ◽  
Christian P. Speer ◽  
Helge Hebestreit
Keyword(s):  
Connective Tissue ◽  
Short Stature ◽  
Connective Tissue Disorder ◽  
Joint Hypermobility ◽  
Compound Heterozygous ◽  
Ehlers Danlos Syndrome ◽  
Craniofacial Features ◽  
Chain Synthesis ◽  
Compound Heterozygous Variants ◽  
Danlos Syndrome

Abstract Background The spondylodysplastic Ehlers-Danlos subtype (OMIM #130070) is a rare connective tissue disorder characterized by a combination of connective tissue symptoms, skeletal features and short stature. It is caused by variants in genes encoding for enzymes involved in the proteoglycan biosynthesis or for a zinc transporter. Presentation of cases We report two brothers with a similar phenotype of short stature, joint hypermobility, distinct craniofacial features, developmental delay and severe hypermetropia indicative for a spondylodysplastic Ehlers-Danlos subtype. One also suffered from a recurrent pneumothorax. Gene panel analysis identified two compound heterozygous variants in the B4GALT7 gene: c.641G > A and c.723 + 4A > G. B4GALT7 encodes for galactosyltransferase I, which is required for the initiation of glycosaminoglycan side chain synthesis of proteoglycans. Conclusions This is a first full report on two cases with spondylodysplastic Ehlers-Danlos syndrome and the c.723 + 4A > G variant of B4GALT7. The recurrent pneumothoraces observed in one case expand the variable phenotype of the syndrome.

scholarly journals Ehlers-Danlos Syndrome, Hypermobility Type, Is Linked to Chromosome 8p22-8p21.1 in an Extended Belgian Family

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Delfien Syx ◽  
Sofie Symoens ◽  
Wouter Steyaert ◽  
Anne De Paepe ◽  
Paul J. Coucke ◽  
...  
Keyword(s):  
Rare Variants ◽  
Missense Variant ◽  
Joint Hypermobility ◽  
Joint Hypermobility Syndrome ◽  
Ehlers Danlos Syndrome ◽  
Genome Wide ◽  
Whole Exome ◽  
A Genome ◽  
Hereditary Conditions ◽  
Danlos Syndrome

Joint hypermobility is a common, mostly benign, finding in the general population. In a subset of individuals, however, it causes a range of clinical problems, mainly affecting the musculoskeletal system. Joint hypermobility often appears as a familial trait and is shared by several heritable connective tissue disorders, including the hypermobility subtype of the Ehlers-Danlos syndrome (EDS-HT) or benign joint hypermobility syndrome (BJHS). These hereditary conditions provide unique models for the study of the genetic basis of joint hypermobility. Nevertheless, these studies are largely hampered by the great variability in clinical presentation and the often vague mode of inheritance in many families. Here, we performed a genome-wide linkage scan in a unique three-generation family with an autosomal dominant EDS-HT phenotype and identified a linkage interval on chromosome 8p22-8p21.1, with a maximum two-point LOD score of 4.73. Subsequent whole exome sequencing revealed the presence of a unique missense variant in theLZTS1gene, located within the candidate region. Subsequent analysis of 230 EDS-HT/BJHS patients resulted in the identification of three additional rare variants. This is the first reported genome-wide linkage analysis in an EDS-HT family, thereby providing an opportunity to identify a new disease gene for this condition.

scholarly journals Classification, nosology and diagnostics of Ehlers-Danlos syndrome

2019 ◽  
Vol 5 (2) ◽  
pp. 34-46
Author(s):  
Ben C J Hamel
Keyword(s):  
New York ◽  
Connective Tissue ◽  
Joint Hypermobility ◽  
Multidisciplinary Teams ◽  
Connective Tissue Disorders ◽  
Joint Hypermobility Syndrome ◽  
Ehlers Danlos Syndrome ◽  
Skin Fragility ◽  
Danlos Syndrome ◽  
Heritable Connective Tissue Disorders

Ehlers-Danlos syndrome (EDS) comprises a group of heritable connective tissue disorders which has as cardinal features varying degrees of skin hyperextensibility, joint hypermobility, easy bruising and skin fragility. The 2017 New York nosology distinguishes 13 types of EDS, which all, except hypermobile EDS, have a known molecular basis. Hypermobile EDS is recognized as a common and often disabling disorder, incorporating benign joint hypermobility syndrome. EDS needs to be differentiated from other connective tissue disorders, in particular Marfan syndrome, Loeys-Dietz syndrome and cutis laxa. The frequent types of EDS can be diagnosed after careful history taking and clinical examination, but for definite diagnosis molecular confirmation is needed in all types. Management for EDS patients preferably is provided by multidisciplinary teams in expertise centres. After diagnosing EDS genetic counselling is an essential part of the management of patients and their family.

scholarly journals Ehlers-Danlos Syndrome, Hypermobility Type: An Underdiagnosed Hereditary Connective Tissue Disorder with Mucocutaneous, Articular, and Systemic Manifestations

2012 ◽  
Vol 2012 ◽  
pp. 1-22 ◽  
Author(s):  
Marco Castori
Keyword(s):  
Connective Tissue ◽  
Correct Diagnosis ◽  
Connective Tissue Disorder ◽  
Joint Hypermobility ◽  
Joint Hypermobility Syndrome ◽  
Ehlers Danlos Syndrome ◽  
Point Of Interest ◽  
Wide Range ◽  
Systemic Manifestations ◽  
Danlos Syndrome

Ehlers-Danlos syndrome, hypermobility type, constituting a phenotypic continuum with or, perhaps, corresponding to the joint hypermobility syndrome (JHS/EDS-HT), is likely the most common, though the least recognized, heritable connective tissue disorder. Known for decades as a hereditary condition with predominant rheumatologic manifestations, it is now emerging as a multisystemic disorder with widespread manifestations. Nevertheless, the practitioners’ awareness of this condition is generally poor and most patients await years or, perhaps, decades before reaching the correct diagnosis. Among the various sites of disease manifestations, skin and mucosae represent a neglected organ where the dermatologist can easily spot diagnostic clues, which consistently integrate joint hypermobility and other orthopedic/neurologic manifestations at physical examination. In this paper, actual knowledge on JHS/EDS-HT is summarized in various sections. Particular attention has been posed on overlooked manifestations, including cutaneous, mucosal, and oropharyngeal features, and early diagnosis techniques, as a major point of interest for the practicing dermatologist. Actual research progresses on JH/EDS-HT envisage an unexpected link between heritable dysfunctions of the connective tissue and a wide range of functional somatic syndromes, most of them commonly diagnosed in the office of various specialists, comprising dermatologists.

scholarly journals Effects of Rhythmic Sensory Stimulation on Ehlers–Danlos Syndrome: A Pilot Study

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Veronica Vuong ◽  
Abdullah Mosabbir ◽  
Denise Paneduro ◽  
Larry Picard ◽  
Hanna Faghfoury ◽  
...  
Keyword(s):  
Pilot Study ◽  
Sensory Stimulation ◽  
Connective Tissue Disorder ◽  
Joint Hypermobility ◽  
Pain Interference ◽  
Depression Symptoms ◽  
Open Label ◽  
Ehlers Danlos Syndrome ◽  
Low Frequencies ◽  
Danlos Syndrome

Ehlers–Danlos syndrome (EDS) is a connective tissue disorder characterized by joint hypermobility and skin extensibility and is often accompanied by chronic pain. Rhythmic sensory stimulation (RSS) can be defined as the stimulation of the senses in a periodic manner within a range of low frequencies. Music plus sound delivered through a vibroacoustic device is a form of RSS and has demonstrated utility in managing pain. In this current study, we conducted an open-label pilot study of 15 patients with hypermobile EDS using RSS as the intervention. Posttreatment improvements were seen in 11 of the 15 patients (73%), whereas 3 of the 15 patients (20%) experienced worse outcomes. Of the 14 patients that completed the experiment, 6 participants (43%) were classified as “responders” to the device while 8 participants (57%) were classified as “nonresponders.” Responders demonstrated significant improvements in pain interference (51.5 ± 16 preintervention vs. 43.5 ± 16.4 postintervention BPI score) and depression symptoms (34.0 ± 15.9 preintervention vs. 26.8 ± 12.1 postintervention CESD score). Poststudy interviews confirm the improvements of pain interference, mood, and bowel symptoms. Furthermore, analysis of medical conditions within the responder group indicates that the presence of depression, anxiety, irritable bowel syndrome, and fibromyalgia may indicate a greater likelihood for patients to benefit with vibroacoustic applications. These results indicate a possible potential for RSS, delivered using a vibroacoustic device, in managing pain-related symptoms. Further research is necessary to elucidate the exact mechanism behind the physiological benefits of RSS.

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.

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