A homozygous
            
              ADAMTS
              2
            
            nonsense mutation in a Doberman Pinscher dog with Ehlers Danlos syndrome and extreme skin fragility

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.

Download Full-text

Multifocal periapical cement dysplasia in Ehlers-Danlos Typ VIII combined with leukoencephalopathy in de novo-mutation of c.890G>A, G297D [pEDS]

10.22541/au.163406388.82809286/v1 ◽

2021 ◽

Author(s):

Manfred Nilius ◽

MInou Nilius ◽

Charlotte Mueller ◽

Guenter Lauer ◽

Berit Koch ◽

...

Keyword(s):

De Novo ◽

De Novo Mutation ◽

Joint Mobility ◽

Syndrome Type ◽

Ehlers Danlos Syndrome ◽

Type Viii ◽

Attached Gingiva ◽

Skin Fragility ◽

Danlos Syndrome

Periodontal Ehlers-Danlos syndrome type VIII (pEDS) is rare and caused by mutation in complement 1 subunit. Lack of attached gingiva, pretibial plaques, joint mobility, skin fragility, and easy bruising consolidate the diagnosis. We describe a case of de novo-mutation of pEDS with generalized periapical cemento dysplasia (PCD) and leukoencephalopathy.

Download Full-text

Cutaneous Asthenia in a Domestic Cat (Felis silvestris catus)

Acta Scientiae Veterinariae ◽

10.22456/1679-9216.110142 ◽

2021 ◽

Vol 49 ◽

Author(s):

Ana Cláudia De Souza Andrade ◽

Laisa Marina Rosa Rey ◽

Isabela Carvalho dos Santos ◽

Sarah Gabriella Delallo Charnovski ◽

Diogo Czornobai ◽

...

Keyword(s):

Diabetes Mellitus ◽

Rare Disease ◽

Clinical Signs ◽

The Body ◽

Domestic Cat ◽

Ehlers Danlos Syndrome ◽

Veterinary Clinic ◽

Skin Fragility ◽

History Of ◽

Danlos Syndrome

Background: Cutaneous asthenia or Ehlers-Danlos syndrome is an inherited and rare disease. This infirmity is from an autosomal mutation that influences the collagen synthesis of the carrier. Thus, its skeleton, formed of fibers, is structurally defective. The disease is characterized by hyperelasticity and skin fragility, leading to lesions throughout the skin. The lesions may manifest in specific places or in a generalized way, being more frequent in the limbs, neck, and back. This disease does not have a specific treatment, only management care to avoid new traumas.Case: A 3-year-old male castrated, no defined race cat, was attended at one veterinary clinic with a history of intense itching. The rapid tests for feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) were negative. On physical examination, infestation by fleas, lesions all over the body, and skin hyperelasticity were observed. Topical treatment for ectoparasites as well as for body wounds was established. After the treatment, he returned without itching, but with the complaints of new lesions that did not heal. The patient underwent a total shearing to facilitate the treatment of the skin, and then he underwent blood tests, biochemistry, hormonal tests, and ultrasound, which showed no suggestive changes for hyperadrenocorticism and diabetes mellitus. His clinical signs, besides not matching with these diseases, also did not indicate skin fragility due to his history of age and balanced diet. The confirmation of the cutaneous asthenia syndrome was acquired through biopsy of skin fragment, in which it was observed disarray of collagen fibers, hypertrophy, and fibroblast hyperplasia, together with the rate of extensibility of the skin where the value reached the mark of 27.5%. Throughout the hospitalization, it was noted the progression of the disease with the appearance of new lesions, where there was no bleeding and they appeared even with the patient wearing padded clothes. Its progression lasted one year until the patient's euthanasia.Discussion: For the disposal of diabetes mellitus and hyperadrenocorticism as causes of the appearance of lesions by the body in the patient, he was submitted to the suppression tests with dexamethasone, in which he presented normality, in the biochemical examination it was dosed with fructosamine and glucose. The fructosamine was in the reference value, but the glucose was slightly altered, this increase may have been a result of stress at the time of blood collection. In addition to the patient not showing specific clinical signs such as polyphagia, polyuria, polydipsia, and weight loss, these are characteristic clinical signs of the disease. For the diagnosis of Ehlers-Danlos syndrome, histological examination, and calculation of the skin extensibility index were used, where the results obtained confirmed the suspicion. This genetic anomaly has no treatment, being progressive, so only environmental management is done to mitigate the appearance of the lesions and provide animal welfare. This case report contributes to aggregating the scientific literature in the area of veterinary medicine since skin asthenia is a rare disease and when its extent is total it becomes even more atypical. The availability of this article will provide a vision of palliative treatment for other cases, demonstrating the progressive nature of the lesions and the methods of diagnosis. Keywords: cat, collagen deficiency, ehlers-danlos syndrome, hyperelastic, skin.

Download Full-text

Systematic investigation of the skin in Chst14−/− mice: A model for skin fragility in musculocontractural Ehlers–Danlos syndrome caused by CHST14 variants (mcEDS-CHST14)

Glycobiology ◽

10.1093/glycob/cwaa058 ◽

2020 ◽

Author(s):

Takuya Hirose ◽

Shuji Mizumoto ◽

Ayana Hashimoto ◽

Yuki Takahashi ◽

Takahiro Yoshizawa ◽

...

Keyword(s):

Chondroitin Sulfate ◽

Anion Exchange ◽

Dermatan Sulfate ◽

Systematic Investigation ◽

Exchange Chromatography ◽

Collagen Fibrils ◽

Loss Of Function ◽

Ehlers Danlos Syndrome ◽

Skin Fragility ◽

Danlos Syndrome

Abstract Loss-of-function variants in CHST14 cause a dermatan 4-O-sulfotransferase deficiency named musculocontractural Ehlers–Danlos syndrome-CHST14 (mcEDS-CHST14), resulting in complete depletion of the dermatan sulfate moiety of decorin glycosaminoglycan (GAG) chains, which is replaced by chondroitin sulfate. Recently, we uncovered structural alteration of GAG chains in the skin of patients with mcEDS-CHST14. Here, we conducted the first systematic investigation of Chst14 gene-deleted homozygote (Chst14−/−) mice. We used skin samples of wild-type (Chst14+/+) and Chst14−/− mice. Mechanical fragility of the skin was measured with a tensile test. Pathology was observed using light microscopy, decorin immunohistochemistry and electron microscopy (EM) including cupromeronic blue (CB) staining. Quantification of chondroitin sulfate and dermatan sulfate was performed using enzymatic digestion followed by anion-exchange HPLC. In Chst14−/− mice, skin tensile strength was significantly decreased compared with that in Chst14+/+ mice. EM showed that collagen fibrils were oriented in various directions to form disorganized collagen fibers in the reticular layer. Through EM-based CB staining, rod-shaped linear GAG chains were found to be attached at one end to collagen fibrils and protruded outside of the fibrils, in contrast to them being round and wrapping the collagen fibrils in Chst14+/+ mice. A very low level of dermatan sulfate disaccharides was detected in the skin of Chst14−/− mice by anion-exchange chromatography. Chst14−/− mice, exhibiting similar abnormalities in the GAG structure of decorin and collagen networks in the skin, could be a reasonable model for skin fragility of patients with mcEDS-CHST14, shedding light on the role of dermatan sulfate in maintaining skin strength.

Download Full-text

Classification, nosology and diagnostics of Ehlers-Danlos syndrome

Journal of Biomedicine and Translational Research ◽

10.14710/jbtr.v5i2.4531 ◽

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.

Download Full-text

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

Animals ◽

10.3390/ani10112002 ◽

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.

Download Full-text