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Classical EDS is a heritable disorder of connective tissue. Patients are affected with joint hypermobility, skin hyperextensibilty, and skin fragility leading to atrophic scarring and significant bruising. These clinical features suggest consideration of the diagnosis which then needs to be confirmed, preferably by genetic testing. The most recent...
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... hyperextensibility has been shown to be a reliable and reproducible feature of classical EDS [Remvig et al., 2010]. This group confirmed that patients with classical EDS show extensibility beyond the normal range (Fig. 1). However, they found skin consistency to be an unreliable test and concluded that skin consistency should not be included in the diagnostic criteria for classical EDS. Other reports have also found skin hyperextensibility to be a good indicator for classical EDS, as it quite specific to this diagnosis [Heidbreder et al., 2008;Catala-P ...
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Ehlers–Danlos syndrome (EDS) is a heritable connective tissue disorder characterized by a varying degree of skin hyperextensibility and joint hypermobility. EDS is classified into 13 subtypes according to the most recent classification. These subtypes are clinically and genetically heterogenous. The spondylodysplastic subvariety of EDS (spEDS) is c...
The Ehlers–Danlos syndromes comprise a clinically and genetically heterogeneous group of heritable connective tissue disorders, which are characterized by joint hypermobility, skin hyperextensibility, and tissue friability. In the Villefranche Nosology, six subtypes were recognized: The classical, hypermobile, vascular, kyphoscoliotic, arthrochalas...
Classical Ehlers-Danlos syndrome (cEDS) is a rare inherited autosomal dominant connective tissue disorder with core clinical features including skin hyperextensibility, abnormal scarring, and generalized joint hypermobility. Classical EDS is predominantly caused by small pathogenic variants in the genes COL5A1 and COL5A2 and occasionally by a COL1A...
Ehlers-Danlos syndrome (EDS) is a group of clinically and genetically heterogeneous heritable connective tissue disorders (Yeowell and Pinnell 1993) affecting the skin, ligaments, joints, blood vessels, and internal organs. EDS is characterized by skin extensibility, joint hypermobility (JHM), and tissue fragility. EDS results from mutations in gen...
Ehlers–Danlos syndrome (EDS) is a clinically and genetically heterogeneous group of heritable connective tissue disorders (HCTDs) defined by joint laxity, skin alterations, and joint hypermobility. The latest EDS classification recognized 13 subtypes in which the clinical and genetic phenotypes are often overlapping, making the diagnosis rather dif...
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... While the contingencies of disease pattern will never match the controlled insights from experimental study, a holistic documentation of symptoms and their translation into the pathogenetic mechanism can allow us to focus on molecular investigation. Such is the case when the full panoply of tissue laxity [4][5][6][7][8], autonomic [9][10][11], and neuromuscular [12,13] findings are ascertained in connective tissue dysplasias [8], whereby the appreciation of Ehlers-Danlos syndrome (EDS) is linked with its genetic variation to central articulo-autonomic dysplasia mechanisms [2,[9][10][11] instead of peripheral phenotypes [4][5][6][7][8]. ...
... While the contingencies of disease pattern will never match the controlled insights from experimental study, a holistic documentation of symptoms and their translation into the pathogenetic mechanism can allow us to focus on molecular investigation. Such is the case when the full panoply of tissue laxity [4][5][6][7][8], autonomic [9][10][11], and neuromuscular [12,13] findings are ascertained in connective tissue dysplasias [8], whereby the appreciation of Ehlers-Danlos syndrome (EDS) is linked with its genetic variation to central articulo-autonomic dysplasia mechanisms [2,[9][10][11] instead of peripheral phenotypes [4][5][6][7][8]. ...
... Clinical and molecular analyses of the 1899 patients diagnosed with EDS over a 10-year period from 2011 to 2020 are summarized in Table 1, expanded from preliminary reports [2,11] as described in Methods. Table S1 shows frequencies of 80 history and 40 history findings systematically assessed on checklist forms, which included 12 history, 7 physical categories, and 28 consensus findings of EDS [4,6,58]. Although this observational data on 1261 patients are biased by referral to a medical geneticist focused on EDS, a common profile for EDS patients that transcends type or molecular change is suggested by similar finding frequencies in patients referred from orthopedic, rheumatologic, or cardiology subspecialists (manuscript in preparation- [11,56]). ...
A substantial fraction of the 15% with double-jointedness or hypermobility have the traditionally ascertained joint-skeletal, cutaneous, and cardiovascular symptoms of connective tissue dysplasia and its particular manifestation as Ehlers-Danlos syndrome (EDS). The holistic ascertainment of 120 findings in 1261 EDS patients added neuro-autonomic symptoms like headaches, muscle weakness, brain fog, chronic fatigue, dyspnea, and bowel irregularity to those of arthralgia and skin laxity, 15 of these symptoms shared with those of post-infectious SARS-CoV-2 (long COVID-19). Underlying articulo-autonomic mechanisms guided a clinical qualification protocol that qualified DNA variants in 317 genes as having diagnostic utility for EDS, six of them identical (F2-LIFR-NLRP3-STAT1-T1CAM1-TNFRSF13B) and eighteen similar to those modifying COVID-19 severity/EDS, including ADAMTS13/ADAMTS2-C3/C1R-IKBKG/IKBKAP-PIK3C3/PIK3R1-POLD4/POLG-TMPRSS2/TMPRSS6-WNT3/WNT10A. Also, contributing to EDS and COVID-19 severity were forty and three genes, respectively, impacting mitochondrial functions as well as parts of an overlapping gene network, or entome, that are hypothesized to mediate the cognitive-behavioral, neuro-autonomic, and immune-inflammatory alterations of connective tissue in these conditions. The further characterization of long COVID-19 natural history and genetic predisposition will be necessary before these parallels to EDS can be carefully delineated and translated into therapies.
... 6 Patient education is essential to avoid traumatic activities that could provoke injuries. 8 Genetic counselling is also recommended to the Classical EDS, as the affected individuals have a 50% chance of passing on the disease in each pregnancy. 8 Considering the skin changes and the negative impact on the quality of life associated with these manifestations, we performed a microfocused ultrasound on the patient described to improve his skin complaints. ...
... 8 Genetic counselling is also recommended to the Classical EDS, as the affected individuals have a 50% chance of passing on the disease in each pregnancy. 8 Considering the skin changes and the negative impact on the quality of life associated with these manifestations, we performed a microfocused ultrasound on the patient described to improve his skin complaints. Due to the vascular fragility and high risk of bleeding in the EDS, we avoided the collagen stimulation through injectable products and have focused on a non-invasive treatment for skin laxity. ...
... The discolouration may represent post-inflammatory hyperpigmentation after injury or inflammatory disorder of the skin. However, the symmetrical distribution seen in 14/17 (82%) individuals and level of hyperpigmentation is not in keeping with a purely trauma related process post-injury as is seen in other rare EDS types such as classical EDS (Bowen et al., 2017). Some individuals do not recall significant trauma to their lower limbs in the pattern of discolouration. ...
... Vitamin C use has been recommended as a method to possibly reduce bruising in different types of EDS. It is known to be involved and potentially increase collagen production by fibroblasts (Tajima and Pinnell, 1996;Bowen et al., 2017), however there is no current clinical evidence that it reduces bruising frequency or severity. Given that the pathophysiological mechanism of pEDS remains unclear, the role for this supplement in pEDS related bruising is unknown. ...
Introduction: Periodontal Ehlers-Danlos Syndrome (pEDS) is a rare autosomal dominant type of EDS characterised by severe early-onset periodontitis, lack of attached gingiva, pretibial plaques, joint hypermobility and skin hyperextensibility as per the 2017 International EDS Classification. In 2016, deleterious pathogenic heterozygous variants were identified in C1R and C1S , which encode components of the complement system.
Materials and Methods: Individuals with a clinical suspicion of pEDS were clinically and molecularly assessed through the National EDS Service in London and Sheffield and in genetic services in Austria, Sweden and Australia. Transmission electron microscopy and fibroblast studies were performed in a small subset of patients.
Results: A total of 21 adults from 12 families were clinically and molecularly diagnosed with pEDS, with C1R variants in all families. The age at molecular diagnosis ranged from 21–73 years (mean 45 years), male: female ratio 5:16. Features of easy bruising (90%), pretibial plaques (81%), skin fragility (71%), joint hypermobility (24%) and vocal changes (38%) were identified as well as leukodystrophy in 89% of those imaged.
Discussion: This cohort highlights the clinical features of pEDS in adults and contributes several important additional clinical features as well as novel deleterious variants to current knowledge. Hypothetical pathogenic mechanisms which may help to progress understanding and management of pEDS are also discussed.
... The most commonly described issues include joint hypermobility, skin elasticity, and musculoskeletal manifestations. The most common subtypes of EDS are classical, classical-like, hypermobile, cardio-valvular, and vascular creating a prevalence of one in 5,000 people worldwide [1,2,3,4,5,6]. Treatment for EDS is often limited to supportive measures with medications targeting pain, anti-inflammatory, and cardiovascular symptoms, as well as complications [7,8,9,10]. ...
... This may be due to recent improvements in awareness and diagnoses, as well as possible contraindications related to hypermobility and tissue fragility. The goal of OMT is to restore physiologic motion and function, and it may be particularly beneficial in patients prone to structural restrictions from atypical connective tissues [1,2,3,6,11]. This case report aims to describe the response of an EDS patient to outpatient OMT conducted in a series of three visits. ...
... Recently, patients with EDS have been presenting with increased difficulty breathing and GI dysfunction. The disruption of collagen integrity brings about systemic disease as described in the literature, requiring increased interdisciplinary approaches to treatment [1,2,5]. Current treatment protocols include physical therapy, occupational therapy, pain management, and symptomatic treatment. ...
Ehlers-Danlos syndrome (EDS) is a disorder affecting connective tissue throughout the body. Inherited through several different genetic mutations, the EDS symptoms of hyperextensibility, hypermobility, and fragility cause significant somatic and visceral issues in those affected. Chronic somatic dysfunction, pain, and systemic involvement create lifelong comorbidities and discomfort for these patients. One in every 5,000 individuals is burdened with EDS worldwide; in the US, the range has been reported to be 1/2,500-1/5,000 people. Very few patients with EDS in the literature have been documented and treated with osteopathic manipulative treatment (OMT). The objective of this case report is to describe the response of an EDS patient to outpatient OMT over a series of three office visits. The patient has verbally consented to OMT at each encounter. A combination of soft tissue manipulation, muscle energy, Still's technique, counterstrain, and high-velocity low-amplitude (HVLA) was performed in the head and neck, thoracic, lumbar, ribs, and lower extremity regions. During the three clinic visits of this patient, OMT was performed in the same regions by the student physician under the supervision of the attending physician. At each visit, the patient was asked to report their pain levels pre- and post-treatment and assess symptom improvement using a one to 10 pain scale, as well as any subjective symptoms they are experiencing. Following each treatment, as well as at each follow-up encounter, the patient reported marked pain and symptom improvement. The objective of this case report is to describe the benefits that one patient experienced from three clinic visits. These results showed that subjective improvement in respiratory, gastrointestinal, and musculoskeletal symptoms secondary to the longstanding history of EDS may be possible through the use of OMT.
... EDS is a group of connective tissue disorders characterized by defective structure or processing of collagen types I, III, and V, whose hallmark clinical features include skin hyperelasticity, joint hypermobility, tissue fragility, easy bruising, and abnormal healing. 1 EDS can be subdivided in at least 13 subtypes, of which the most common are the classic subtype, characterized by significant tissue fragility, and the hypermobile subtype, characterized by significant joint hypermobility. [1][2][3] Of particular importance to surgeons is the vascular subtype, which carries an increased risk of severe perioperative bleeding. 4 Although literature documents relative success and low rates of complications for patients with EDS undergoing elective facial plastic surgery, 4 we present the first report of septorhinoplasty in a patient with EDS. ...
... Such comparisons are expected to enable early detection of the changes in biomechanical properties associated with keratoconus and to aid clinical diagnosis. Some systemic connective tissue diseases that manifest in the eye as keratoconus, as well as keratoconus as a complication of refractive surgery, may also be associated with this pathogenesis [83]. To reduce the probability of keratoconus as a complication refractive surgery, most current refractive procedures restrict postoperative corneal stromal bed thickness to a minimum of 250μm [84]. ...
In early corneal examinations, the relationships between the morphological and biomechanical features of the cornea were unclear. Although consistent links have been demonstrated between the two in certain cases, these are not valid in many diseased states. An accurate assessment of the corneal biomechanical properties is essential for understanding the condition of the cornea. Studies on corneal biomechanics in vivo suggest that clinical problems such as refractive surgery and ectatic corneal disease are closely related to changes in biomechanical parameters. Current techniques are available to assess the mechanical characteristics of the cornea in vivo. Accordingly, various attempts have been expended to obtain the relevant mechanical parameters from different perspectives, using the air-puff method, ultrasound, optical techniques, and finite element analyses. However, a measurement technique that can comprehensively reflect the full mechanical characteristics of the cornea (gold standard) has not yet been developed. We review herein the in vivo measurement techniques used to assess corneal biomechanics, and discuss their advantages and limitations to provide a comprehensive introduction to the current state of technical development to support more accurate clinical decisions.
... Among possible dislocations in EDS, a particularly menacing complication involves the atlantoaxial joint. Instability in the latter can potentially complicate all forms of EDS and has been associated with quadriparesis [21][22][23]. Furthermore, fatigue, muscle hypotonia, (kypho)scoliosis, joint instability, and pain are major determinants of disability, which significantly deteriorates the quality of life of patients with EDS [20]. ...
Kyphoscoliotic Ehlers–Danlos syndrome and 17p13.3 microduplication share multiple clinical features such as muscle hypotonia, cleft palate, and growth impairment. This paper describes a patient who was first diagnosed with the duplication and a decade later also with FKBP14-kEDS. The latter was initially overlooked due to the pathogenic significance attributed to the duplication and to the fact that, at the time of the first diagnosis, this specific form of kEDS had yet to be discovered. The patient’s progressive kyphoscoliosis and severe joint laxity were the clinical features that prompted the patient’s physiatrist to reassess the genetic work-up. This extreme latency caused inaccurate management in the patient’s follow-up program, which ultimately may have resulted in preventable clinical complications. This report underlines the importance of remaining up-to-date with patient status, reviewing old cases, and relying on specialist advice to reach a correct diagnosis.
... Connective tissue disorders are characterized by alterations in the function of the extracellular matrix (ECM), caused by mutation in collagen genes, collagen redoxmodifying enzymes, and/or inflammation (7,8). These ECM factors have been also been associated with mitochondrial function (9)(10)(11)(12). ...
Mitochondrial dysfunction can be associated with a range of clinical manifestations. Here, we report a family with a complex phenotype including combinations of connective tissue, neurological, and metabolic symptoms that were passed on to all surviving children. Analysis of the maternally inherited mtDNA revealed a novel genotype encompassing the haplogroup J - defining mitochondrial DNA (mtDNA) ND5 m.13708G>A (A458T) variant arising on the mtDNA haplogroup H7A background, an extremely rare combination. Analysis of transmitochondrial cybrids with the 13708A-H7 mtDNA revealed a lower mitochondrial respiration, increased reactive oxygen species production (mROS), and dysregulation of connective tissue gene expression. The mitochondrial dysfunction was exacerbated by histamine, explaining why all eight surviving children inherited the dysfunctional histidine decarboxylase allele (W327X) from the father. Thus, certain combinations of common mtDNA variants can cause mitochondrial dysfunction, mitochondrial dysfunction can affect extracellular matrix gene expression, and histamine-activated mROS production can augment the severity of mitochondrial dysfunction. Most important, we have identified a previously unreported genetic cause of mitochondrial disorder arising from the incompatibility of common, nonpathogenic mtDNA variants.
... Although bleeding is related to capillary fragility rather than a clotting disorder, Vasopressin can help in the case of bruising or epistaxis. 18 The differential diagnosis of EDS includes Marfan's syndrome, generalized familial joint hypermobility syndrome, cutis laxa, pseudoxanthoma elasticum, osteogenesis imperfecta, Loeys-Dietz syndrome, Larsen's syndrome, and other congenital connective tissue diseases. 19 ...
Ehlers–Danlossyndrome (EDS) is a group of non-inflammatory hereditary connective tissue diseases that impair collagen and elastin metabolism, resulting in collagen defects and/or disordered deposition in tissues, and can cause a variety of multisystemic symptoms. It has a wide range of genetic origins, molecular abnormalities, and connective tissue ultrastructure (CT). EDS is caused by changes in over 19 genes that are present at birth. The kind of EDS is determined by the gene that is impacted. EDS has been divided into 13 subtypes, with a fourteenth variant reported in 2018. One of the most prevalent manifestations is the hypermobile version (EDSH). Hippocrates first described EDS in the 4thcentury B.C. The syndromes are named after two physicians who described them around the start of the twentieth century: Edvard Ehlers and Henri-Alexandre Danlos. The altered mechanical functions of the involved tissues cause a variety of cutaneous (hyper elasticity, fragility, and atrophy), rheumatological (joint laxity and hypermobility), and vascular (vessel wall fragility and easy bruise) changes. The diagnosis is usually made using a combination of clinical criteria, skin biopsies, and genetic studies. EDS is normally diagnosed at birth or in early childhood, but symptoms can sometimes appear in adolescence or young adulthood. Some gynecologic and obstetric problems are frequent among women. When a patient is identified, a thorough examination of all family members is required. Aortic dissection and joint dislocations are two major complications that can occur.
... Ehlers-Danlos syndrome (EDS) is a connective tissue disorder characterized as impaired collagen metabolism, predominantly involving joints, skin, and blood vessel wall [1]. EDS can be classified into 13 different types based on 20 unique gene mutations, and varying clinical presentations. ...
... EDS can be classified into 13 different types based on 20 unique gene mutations, and varying clinical presentations. The most common clinical presentation includes hypermobility of the joints, hyperelasticity of the skin, and a varying degree of tissue fragility [1]. Vascular complications can arise from EDS, more commonly with vascular EDS (Type IV), and can include rupture of major blood vessels and organs [2]. ...
A 36-year-old woman with Ehlers-Danlos syndrome (EDS) presents with a painful and enlarging right lower extremity mass prompting imaging work up. Herein we present a case report of an uncommon complication and a unique treatment option of a large right anterior tibial artery pseudoaneurysm caused by repetitive microtrauma in a patient with EDS and a congenital club foot.
