Classical-like Ehlers–Danlos syndrome: a clinical description of 20 newly identified individuals with evidence of tissue fragility

Green, Claire; Ghali, Neeti; Akilapa, Rhoda; Angwin, Chloe; Baker, Duncan; Bartlett, Marion; Bowen, Jessica; Brady, Angela; Brock, Joanna; Chamberlain, Erin; Cheema, Harveer; McConnell, Vivienne; Crookes, Renarta; Kazkaz, Hanadi; Johnson, Diana; Pope, F. Michael; Vandersteen, Anthony; Sobey, Glenda; Dijk, Fleur S van

doi:10.1038/s41436-020-0850-1

Cited by 18 publications

(21 citation statements)

References 27 publications

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“…Classical-like EDS (clEDS) is a rare autosomal recessive condition, characterized by generalized joint hypermobility and skin hyperextensibility with easy bruising but without atrophic scarring. Patients harbor biallelic mutations in the TNXB gene, resulting in complete absence of the corresponding tenascin-X (TNX) protein ( Brady et al, 2017 ; Green et al, 2020 ). TNX is a glycoprotein with an architectural function in the ECM and has been shown to localize with collagen fibrils in tendon and dermis ( Valcourt et al, 2015 ).…”

Section: Animal Models Mimicking Ehlers–danlos Syndromesmentioning

confidence: 99%

Animal Models of Ehlers–Danlos Syndromes: Phenotype, Pathogenesis, and Translational Potential

et al. 2021

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The Ehlers–Danlos syndromes (EDS) are a group of heritable connective tissues disorders mainly characterized by skin hyperextensibility, joint hypermobility and generalized tissue fragility. Currently, 14 EDS subtypes each with particular phenotypic features are recognized and are caused by genetic defects in 20 different genes. All of these genes are involved in the biosynthesis and/or fibrillogenesis of collagens at some level. Although great progress has been made in elucidating the molecular basis of different EDS subtypes, the pathogenic mechanisms underlying the observed phenotypes remain poorly understood, and consequentially, adequate treatment and management options for these conditions remain scarce. To date, several animal models, mainly mice and zebrafish, have been described with defects in 14 of the 20 hitherto known EDS-associated genes. These models have been instrumental in discerning the functions and roles of the corresponding proteins during development, maturation and repair and in portraying their roles during collagen biosynthesis and/or fibrillogenesis, for some even before their contribution to an EDS phenotype was elucidated. Additionally, extensive phenotypical characterization of these models has shown that they largely phenocopy their human counterparts, with recapitulation of several clinical hallmarks of the corresponding EDS subtype, including dermatological, cardiovascular, musculoskeletal and ocular features, as well as biomechanical and ultrastructural similarities in tissues. In this narrative review, we provide a comprehensive overview of animal models manifesting phenotypes that mimic EDS with a focus on engineered mouse and zebrafish models, and their relevance in past and future EDS research. Additionally, we briefly discuss domestic animals with naturally occurring EDS phenotypes. Collectively, these animal models have only started to reveal glimpses into the pathophysiological aspects associated with EDS and will undoubtably continue to play critical roles in EDS research due to their tremendous potential for pinpointing (common) signaling pathways, unveiling possible therapeutic targets and providing opportunities for preclinical therapeutic interventions.

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Section: Animal Models Mimicking Ehlers–danlos Syndromesmentioning

confidence: 99%

Animal Models of Ehlers–Danlos Syndromes: Phenotype, Pathogenesis, and Translational Potential

et al. 2021

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“…vascular type); however, intrauterine death and miscarriages have been reported in 7.7-26.3%, and obstetric complications, including post-partum haemorrhage, perineal tear, and uterine/vaginal prolapse, were relatively increased compared with normal individuals. 2,4,5 Our case also had a normal full-term pregnancy course and vaginal delivery without any life-threatening complications.…”

mentioning

confidence: 54%

“…Gastrointestinal manifestations, including gastrointestinal bleeding, rectal prolapse, diverticulitis, and hemorrhoids, have also been reported. 2,4 Because clEDS was newly classified by separation from the hypermobile type of EDS (former classification type III), 1 the statistical insight into the pregnancy in the patient with clEDS was limited.…”

mentioning

confidence: 99%

Novel gross deletion mutation c.‐105_4042+498del in the TNXB gene in a Japanese woman with classical‐like Ehlers–Danlos syndrome: A case of uneventful pregnancy and delivery

Watanabe

Ito

Samura

et al. 2021

The Journal of Dermatology

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“…It has also been reported that clEDS patients exhibit rectal prolapse (18%) and diverticulosis or diverticulitis (18%) as gastrointestinal complications (72). Currently, these gastrointestinal complications are considered to be more common in clEDS patients (73,74).…”

Section: Cleds Caused By Tnx Deficiencymentioning

confidence: 99%

The Roles of Tenascins in Cardiovascular, Inflammatory, and Heritable Connective Tissue Diseases

Matsumoto

Aoki

2020

Front. Immunol.

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Tenascins are a family of multifunctional extracellular matrix (ECM) glycoproteins with time- and tissue specific expression patterns during development, tissue homeostasis, and diseases. There are four family members (tenascin-C, -R, -X, -W) in vertebrates. Among them, tenascin-X (TNX) and tenascin-C (TNC) play important roles in human pathologies. TNX is expressed widely in loose connective tissues. TNX contributes to the stability and maintenance of the collagen network, and its absence causes classical-like Ehlers-Danlos syndrome (clEDS), a heritable connective tissue disorder. In contrast, TNC is specifically and transiently expressed upon pathological conditions such as inflammation, fibrosis, and cancer. There is growing evidence that TNC is involved in inflammatory processes with proinflammatory or anti-inflammatory activity in a context-dependent manner. In this review, we summarize the roles of these two tenascins, TNX and TNC, in cardiovascular and inflammatory diseases and in clEDS, and we discuss the functional consequences of the expression of these tenascins for tissue homeostasis.

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Classical-like Ehlers–Danlos syndrome: a clinical description of 20 newly identified individuals with evidence of tissue fragility

Cited by 18 publications

References 27 publications

Animal Models of Ehlers–Danlos Syndromes: Phenotype, Pathogenesis, and Translational Potential

Animal Models of Ehlers–Danlos Syndromes: Phenotype, Pathogenesis, and Translational Potential

Novel gross deletion mutation c.‐105_4042+498del in the TNXB gene in a Japanese woman with classical‐like Ehlers–Danlos syndrome: A case of uneventful pregnancy and delivery

The Roles of Tenascins in Cardiovascular, Inflammatory, and Heritable Connective Tissue Diseases

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