Ehlers-Danlos Syndrome Caused by Tenascin-X Deficiency

Last update 01 Nov 2024

Basic Info

Synonyms

Classical-like EDS type 1, Classical-like Ehlers-Danlos syndrome type 1, EDS DUE TO TNX DEFICIENCY

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Introduction

A type of Ehlers-Danlos syndrome characterized by generalized joint hypermobility, skin hyperextensibility and easy bruising without atrophic scarring. Other common features include foot and hand deformities (piezogenic papules, pes planus, broad forefeet, brachydactyly, and acrogenic skin of hands), severe fatigue and neuromuscular symptoms including muscle weakness and myalgia. Caused by homozygous or heterozygous mutation in the tenascin-XB gene on chromosome 6p21.

100 Clinical Results associated with Ehlers-Danlos Syndrome Caused by Tenascin-X Deficiency

100 Translational Medicine associated with Ehlers-Danlos Syndrome Caused by Tenascin-X Deficiency

0 Patents (Medical) associated with Ehlers-Danlos Syndrome Caused by Tenascin-X Deficiency

Literatures (Medical) associated with Ehlers-Danlos Syndrome Caused by Tenascin-X Deficiency

01 Jan 2023·Frontiers in genetics

Case report: further delineation of AEBP1-related Ehlers-Danlos Syndrome (classical-like EDS type 2) in an additional patient and comprehensive clinical and molecular review of the literature.

Author: Hayashi, Shujiro ; Motegi, Sei-Ichiro ; Nagai, So ; Yamaguchi, Tomomi ; Kosho, Tomoki ; Uchiyama, Akihiko ; Fujikawa, Tomomi ; Takiguchi, Yuri

The Ehlers-Danlos Syndromes (EDS), a group of hereditary connective tissue disorders, were classified into 13 subtypes in the 2017 International Classification. Recently, a new subtype of EDS called classical-like EDS type 2 (clEDS2), which is caused by biallelic variants in the adipocyte enhancer binding protein 1 (AEBP1) gene, was identified. We describe the 11th patient (9th family) with clEDS2, who was complicated by a critical vascular event (superior mesenteric artery aneurysm and rupture). A next-generation sequencing panel-based analysis revealed compound heterozygous variants in AEBP1: NM_001129.5:c.[2296G>T]; [2383dup], p.[(Glu766*)]; [(Glu795Glyfs*3)]. Light microscopic analyses showed increased interfibrillar spaces in the reticular dermis, a disorganized arrangement of collagen fibers, and decreased collagen content. An electron microscopic analysis showed the presence of collagen fibrils with irregular contours (flower-like appearance) and small collagen fibrils. A biochemical analysis showed reduced secretion of type I and type III procollagen. Clinical and molecular features of the current patient and all previously reported patients were reviewed comprehensively. Manifestations noted in most cases (>80%) included skin features (hyperextensibility, atrophic scars, easy bruising, excessive skin/skin folding, delayed wound healing, translucency, piezogenic papules), skeletal features (generalized joint hypermobility, dislocations/subluxations, pes planus), dental abnormalities, and neuromuscular abnormalities. Critical complications, each occurring in a single case, included superior mesenteric artery multiple aneurysm and rupture, aortic root dilation requiring surgery, and bowel rupture. Most AEBP1 variants were predicted or experimentally confirmed to lead to nonsense-mediated mRNA decay, whereas one variant resulted in a protein that was retained intracellularly and not secreted. Clinical, molecular, pathological, and biochemical features of the current patient, as well as a review of all previously reported patients, suggest the importance of the aortic carboxypeptidase-like protein encoded by AEBP1 in collagen fibrillogenesis.

01 Jan 2023·Frontiers in genetics

Case report: Two individuals with AEBP1-related classical-like EDS: Further clinical characterisation and description of novel AEBP1 variants.

Author: van Dijk, Fleur Stephanie ; Angwin, Chloe ; Ghali, Neeti

Introduction: AEBP1-related classical-like EDS (clEDS type 2) is a rare type of Ehlers-Danlos syndrome (EDS) that was first reported in 2016. There are overlapping clinical features with TNXB-related classical-like EDS (or clEDS type 1), including skin hyperextensibility, joint hypermobility, and easy bruising. There are currently nine reported individuals with AEBP1-related clEDS type 2. This report confirms previous findings and provides additional clinical and molecular data on this group of individuals. Materials and methods: Two individuals (P1 and P2), with features of a rare type of EDS, were clinically assessed in the London national EDS service and underwent genetic testing. Results: Genetic testing in P1 revealed likely pathogenic AEBP1 variants: c.821del:p. (Pro274Leufs*18) and c.2248T>C:p. (Trp750Arg). In P2 pathogenic AEBP1 variants, c.1012G>T:p. (Glu338*) and c.1930C>T:p. (Arg644*) were identified. Discussion: These two individuals increased the reported number of individuals with AEBP1-related clEDS to 11 (six females and five males). There are shared features with previously reported individuals, including hypermobility (11/11), skin hyperextensibility (11/11), presence of atrophic scarring (9/11), and easy bruising (10/11). In P1, a chronic right vertebral artery dissection, mild dilatation of the splenic artery, aberrant subclavian artery, and tortuous iliac arteries were observed at the age of 63 years. Cardiovascular disease has been reported, including mitral valve prolapse (4/11), peripheral arterial disease (1/11), and aortic root aneurysm requiring surgical intervention (1/11). Hair loss has been reported in 6/11 individuals (five females and one male), only one of which was documented to have a formal diagnosis of androgenetic alopecia, while other individuals were described as having thinning of hair, male pattern hair loss, or unspecified alopecia. Conclusion: The clinical features of individuals with AEBP1-related EDS have not been fully elucidated yet. Hair loss is present in 6/11 individuals with AEBP1-related clEDS and appears to be a feature of this condition. This is the first time hair loss has been formally reported as a characteristic feature in a rare type of EDS. Cardiovascular surveillance seems warranted in this condition because 2/11 individuals have evidence of arterial aneurysm and/or dissection. Further descriptions of affected individuals are necessary to update diagnostic criteria and management guidelines.

01 Jan 2021·Advances in Experimental Medicine and BiologyQ4 · MEDICINE

Connective Tissue Disorders in Domestic Animals

Q4 · MEDICINE

Article

Author: Roberts, Jennifer Hope ; Halper, Jaroslava

Though soft tissue disorders have been recognized and described to some detail in several types of domestic animals and small mammals for some years, they remain uncommon. Because of their low prevalence, not much progress has been made not only in improved diagnosis but also in our understanding of the biochemical basis and pathogenesis of these diseases in animals. Ehlers-Danlos syndrome (EDS) described in dogs already in 1943 and later in cats has only minor impact on the well-being of the dog as its effects on skin of these animals are rather limited. The involved skin is thin and hyperextensible with easily inflicted injuries resulting in hemorrhagic wounds and atrophic scars. Joint laxity and dislocation common in people are less frequently found in dogs. No systemic complications, such as organ rupture or cardiovascular problems which have devastating consequences in people have been described in cats and dogs. The diagnosis is based on clinical presentation and on light or electron microscopic features of disorganized and fragmented collagen fibrils. Several case of bovine and ovine dermatosparaxis analogous to human Ehlers-Danlos syndrome type VIIC were found to be caused by mutations in the procollagen I N-proteinase (pnPI) or ADAMTS2 gene, though mutations in other sites are likely responsible for other types of dermatosparaxis. Cattle suffering from a form of Marfan syndrome (MFS) were described to have aortic dilatation and aneurysm together with ocular abnormalities and skeletal involvement. As in people, mutations at different sites of bovine FBN1 may be responsible for Marfan phenotype. Hereditary equine regional dermal asthenia (HERDA), or hyperelastosis cutis, has been recognized in several horse breeds as affecting primarily skin, and, occasionally, tendons. A mutation in cyclophilin B, a chaperon involved in proper folding of collagens, has been identified in some cases. Warmblood fragile foal syndrome (WFFS) is another Ehlers-Danlos-like disorder in horses, affecting primarily Warmbloods who present with skin fragility and joint hyperextensibility. Degenerative suspensory ligament desmitis (DSLD) affects primarily tendons and ligaments of certain horse breeds. Data from our laboratory showed excessive accumulation of proteoglycans in organs with high content of connective tissues. We have identified increased presence of bone morphogenetic protein 2 (BMP2) in active foci of DSLD and an abnormal form of decorin in proteoglycan deposits. Our most recent data obtained from next generation sequencing showed disturbances in expression of genes for numerous proteoglycans and collagens.

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Ehlers-Danlos Syndrome Caused by Tenascin-X Deficiency

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