Symptoma

Ehlers-Danlos Syndrome

The Ehlers-Danlos syndrome refers to a group of rare, inherited connective tissue disorders that affect collagen structure and function, marked by hyperplasticity of skin, tissue fragility and hyper-flexible joints.

In the classic type, the skin is hyperelastic, fragile and smooth and velvety to touch. Skin is prone to rupturing even after minor trauma. The joints are hyperextendable. Joint dislocations are common. Wound healing is impaired. Other signs and symptoms include:

In hypermobility type, grotesque contortions are seen, such as bending the thumb backwards to touch the forearm or bending the knee almost at a right angle. Chronic pain, joint dislocations and joint hypermobility are other manifestations. Bowel disorders might also be seen.

The vascular type manifests as

In kyphoscoliosis type, the manifestations are:

In arthrochalasia variant, the following findings are present.

The dermatosparaxis type shows up as:

  • Easy Bruising

    Skin hyperextensibility, easy bruising, tissue fragility, atrophic scars, loss of muscle tone, Kyphoscoliosis, and osteopenia (bones which are less dense than normal) are also possible clinical manifestations. [rarediseases.about.com]

    Ehlers-Danlos syndrome (EDS) is associated with easy bruising and bleeding complications in the majority. [ncbi.nlm.nih.gov]

    Easy bruising. Wide atrophic scars. Joint hypermobility.Lesser effect on internal organs Autosomal dominant COL5A1 EDS II Same as EDS I but milder COL5A2 Hypermobility type EDS III Soft, smooth and velvety skin. [laeknabladid.is]

    Possible diagnosis of EDS type VIII: Clinical features of EDS VIII such as hyperextensible joints, atrophic scarring, and easy bruising can often overlap with other forms of EDS. [uwcpdx.org]

  • Chronic Fatigue Syndrome

    There is overlap in the symptoms and findings of EDS and chronic fatigue syndrome. A proportion of those with CFS likely have EDS that has not been identified. [ncbi.nlm.nih.gov]

    EDS is considered an “invisible disability” and is often misdiagnosed as other conditions including hypochondriasis, depression, and chronic fatigue syndrome. [diseaseinfosearch.org]

    He specializes in the evaluation and treatment of adolescents and young adults with conditions characterized by chronic fatigue, including chronic fatigue syndrome, orthostatic intolerance, and joint hypermobility. [doi.org]

  • Marfanoid Habitus

    Homocystinuria also results in a Marfanoid habitus but presents with inferior and medial displacement of the lens ( downward and inward )! [amboss.com]

    habitus" which is characterized by long, slender fingers (arachnodactyly); unusually long limbs; and a sunken chest (pectus excavatum) or protruding chest (pectus carinatum) majority of patients with kEDS harbor biallelic mutations in PLOD1; recently [gpnotebook.com]

    Other common features include a "marfanoid habitus" which is characterized by long, slender fingers (arachnodactyly); unusually long limbs; and a sunken chest (pectus excavatum) or protruding chest (pectus carinatum). [rarediseases.info.nih.gov]

  • Mitral Valve Prolapse

    valve prolapse and others) Other types of EDS The other types of EDS are extremely rare. [web.archive.org]

    If mitral valve prolapse is diagnosed, monitoring and screening are indicated to address subacute bacterial endocarditis precautions. [emedicine.medscape.com]

    valve prolapse in the ecocardiographic study. [ncbi.nlm.nih.gov]

    Results of consultations in ophthalmology and cardiology eliminated the possibility of detached retina or mitral valve prolapse. The genetics and rheumatology consults confirmed a diagnosis of EDS type II or III. [cda-adc.ca]

  • Blue Sclera

    sclerae, small jaw, hypertrichosis Dominant COL1A1, COL1A2 Arthrochalasia, type VII A/B (Exon 6 COL1A1/2 ) Dermatosparaxis Type (EDS type VIIC) Soft and very thin, fragile skin (tearing of the skin), stretchy skin, easy bruising, joint hypermobility [uwcpdx.org]

    Other eye symptoms may include nearsightedness ( myopia ), a blueish tint in the white part of the eyes (blue sclera), and retinal detachment. [rarediseases.info.nih.gov]

    Blue sclera. Thin, translucient, fragile skin. Easy bruising. Pes planus. Recurrent joint dislocation.Chronic joint pains. Easy brushing. Varicose veins. Intestinal rupture. Pelvic adhesions. [laeknabladid.is]

    Functional bowel disorders (functional gastritis, irritable bowel syndrome) Gastroparesis Nerve compression disorders (carpal tunnel syndrome, acroparesthesia, neuropathy) Vascular skin conditions: Raynaud's phenomenon, Livedo reticularis Blue sclera [medicalmarijuana.com]

    Osteopenia/osteoporosis, blue sclerae, hernia, pectus deformity, marfanoid habitus, clubfoot, and refractive errors are also frequently observed and form the minor criteria. In comparison, blue sclerae are also observed in LDS. [annalscts.com]

  • Acrogeria

    A slightly extensible, thin and translucent skin, associated with dysmorphic facies, acrogeria, multiple ecchymoses, hypermobility of the small joints, dorsal kyphosis, genu valgum, flat feet, elongated upper limbs, and low muscle tone were all evident [ncbi.nlm.nih.gov]

    Disease definition Ehlers-Danlos syndrome type IV, also known as the vascular type of Ehlers-Danlos syndrome (EDS), is an inherited connective tissue disorder defined by characteristic facial features (acrogeria) in most patients, translucent skin with [orpha.net]

    Other manifestations that may be found in the Vascular Type include: acrogeria (premature aging of the skin of the hands and feet); early onset varicose veins; arteriovenousfistula (an opening between an artery and vein), carotid-cavernousfistula (abnormal [tadcoalition.org]

  • Cutis Laxa

    KEYWORDS: ATP6V0A2-related cutis laxa; Ehlers-Danlos-like skin lesions; autosomal recessive cutis laxa; type 2A (ARCL2A) [ncbi.nlm.nih.gov]

    […] recessive 1B EFEMP2 Del Dup NGS Cutis laxa, autosomal recessive IC LTBP4 Del Dup NGS Cutis laxa, autosomal recessive IIA ATP6V0A2 Del Dup NGS Cutis laxa, autosomal recessive IIIA ALDH18A1 Del Dup NGS Cutis laxa, autosomal recessive, type IIB & type IIIB [ctgt.net]

    Chernogubow: Über einen Fall von Cutis laxa. (Presentation at the first meeting of Moscow Dermatologic and Venerologic Society, Nov 13, 1891.) Monatshefte für praktische Dermatologie, Hamburg, 1892, 14: 76. E. L. Ehlers: Cutis laxa. [whonamedit.com]

    For example, in cutis laxa the skin is loose, hanging, and wrinkled. In cutis hyperelastica, the skin can be pulled away from the body but it does not tear. In Marfan syndrome, the joints are very mobile. [web.archive.org]

    laxa AR 14 16 ELN Cutis laxa, Supravalvular aortic stenosis AD 78 113 FBLN5 Cutis laxa, Macular degeneration, age-related AD/AR 13 22 FBN1 MASS syndrome, Marfan syndrome, Acromicric dysplasia, Geleophysic dysplasia 3 AD 1465 2679 FBN2 Congenital contractural [blueprintgenetics.com]

  • Thin Skin

    skin Dominant C1S, C1R Peridontal, Type VIII Musculocontractural Type Craniofacial dysmorphism, congenital contractures of thumbs and fingers, clubfeet, severe kyphoscoliosis, hypotonia, thin skin, easy bruising, atrophic scarring, joint hypermobility [uwcpdx.org]

    skin transparent skin thin nose protruding eyes thin lips sunken cheeks small chin collapsed lung heart valve problems Doctors may use a series of tests to diagnose EDS (except for hEDS), or rule out other similar conditions. [healthline.com]

    The vascular type manifests as Thin skin Arterial or uterine rupture Bruising Small joint hyperextensibility In kyphoscoliosis type, the manifestations are: Hypotonia Joint laxity Congenital scoliosis Ocular fragility In arthrochalasia variant, the following [symptoma.com]

    Symptoms include: Skin that bruises very easily, thin skin with visible small blood vessels, particularly on the upper chest and legs fragile blood vessels that can bulge or tear, resulting in serious internal bleeding, a risk of organ problems, such [metro.co.uk]

  • Delayed Wound Healing

    Patients with vascular EDS are at higher risk for uterine rupture and postpartum hemorrhage. 8 Some further complications of delivery in EDS include abnormal fetal presentations, delayed wound healing, uterus atonia, hemorrhage, pelvic prolapse, deep [rheumatologyadvisor.com]

    History revealed skin hyperextensibility since early childhood, presence of easy bruisability & delayed wound healing but there was no dislocation of joints or relevant family history. His development milestones were apparently normal. [ncbi.nlm.nih.gov]

    The oral manifestations include increased mucosal fragility, delayed wound healing, early onset generalized periodontitis and temporomandibular joint hypermobility. [jdrr.org]

    wound healing with atrophic scarring. [3] Depending on the type, EDS can be diagnosed through laboratory studies or clinical examination. [emedicine.medscape.com]

  • Petechiae

    (B) Petechiae on the skin after hair removal treatment. (C) Closeup of the skin petechiae, pinpoint non blanching spots. [laeknabladid.is]

    CFIDS / SEID) Fibromyalgia (already mentioned, and very very common, usually an under-diagnosis for HEDS, may be worsened by comorbid occult MCAD of any kind too) EMF sensitivity – and tendency to “blow” nearby electronics Ganglion cysts, Baker’s cysts Petechiae [ohtwist.com]

    압점에 Molluscoid pseudotumors,[17] Petechia[18] 피하 spheroids Livedo reticularis ( 탁해지는 동공, 수정체의 확장) Piezogenic papules[19] 심혈관[편집] 동맥 파열 수술 도중에 혈관이 파열되는 현상[20] 오름 대동맥의 팽창 및 파열[21] 자세 직립성 빈맥 증후군 레이노 현상 정맥류 마음 중심 전도 이상 다른 표현[편집] Hiatial 탈장 위식도역류 위장관 운동 장애 [ko.wikipedia.org]

  • Joint Dislocation

    Joint dislocations are common. Wound healing is impaired. [symptoma.com]

    Causes generalized joint hypermobility, frequent joint dislocations, skin hyperelasticity, easy bruising, tissue fragility, low muscle tone and low bone mineral density. [gillettechildrens.org]

    Symptoms of EDS include: Back pain Double-jointedness Easily damaged, bruised, and stretchy skin Easy scarring and poor wound healing Flat feet Increased joint mobility, joints popping, early arthritis Joint dislocation Joint pain Premature rupture of [nlm.nih.gov]

    […] any time from large vessel rupture Kyphoscoliosis or ocular Type VI 2% of all cases Eye involvement Scoliosis common (curved spine) Arthrochalasia Type VII A and B 3% of all cases Noticeable joint hypermobility but less skin involvement Spontaneous joint [dermnetnz.org]

  • Osteoporosis

    […] prevalent in hypermobile EDS, shows a higher prevalence in a study of patients with hypermobility.2 Its correlation has been demonstrated with chronic fatigue syndrome, fibromyalgia7 anxiety, depression, panic attacks, agoraphobia2,6,8 dysautonomia and osteoporosis [reumatologiaclinica.org]

    Examples include early onset arthritis, osteoporosis, and an inability to stand for more than a few minutes. In extreme cases, patients simply cannot stand unassisted and require a cane or wheelchair for mobility. [massroots.com]

    Soft, hyperextensible skin; joint hypermobility; bruising; normal scar formation Dominant (rare recessives) COL5A1 and COL5A2 Classical EDS Classical-like, 2 Joint and skin laxity, osteoporosis, osteoarthritis, abnormal scarring, joint dislocations Recessive [uwcpdx.org]

    EDS spondylodysplastic type 2 is characterized by kyphoscoliosis, tapered fingers, osteoporosis, aortic aneurysma, and problems with the lungs. [themedicalbiochemistrypage.org]

  • Hyperextensible Joints

    Ehlers-Danlos syndrome (EDS) is a group of heritable disorders characterised by vast clinical heterogeneity ranging from the classic constellation of symptoms including skin hyperextensibility, joint hypermobility and skin fragility to the exceedingly [ncbi.nlm.nih.gov]

    Ehlers-Danlos syndrome (EDS) is a rare hereditary disorder that results in skin hyperextensibility, joint hypermobility, and tissue fragility. This syndrome is caused by a gene defect which results in faulty collagen synthesis. [medcomic.com]

    Clinical manifestations of EDS are most often joint and skin related and may include: Joints Joint hypermobility; loose/unstable joints which are prone to frequent dislocations and/or subluxations; joint pain; hyperextensible joints (they move beyond [ednf.org]

    Both children manifested hyperelastic velvety skin, hyperextensible joints, papyraceous scars, flat feet and ectopic bone formation. [jclinepi.com]

    J Clin Invest. 2001; 107: 1063–1069 Crossref PubMed Scopus (136) Google ScholarSee all References The current classification of Ehlers-Danlos syndrome distinguishes the classic type with skin hyperextensibility, joint hypermobility, and tissue fragility [jpeds.com]

  • Arthralgia

    Arthralgia is a predominant chief complaint that might lead to a diagnosis of HEDS patients. Similarly, arthralgia is also a major complaint in many rheumatological conditions (i.e. [nature.com]

    […] walking Osteopenia (low bone density) Stretchy ligaments and tendons Tearing of tendons or muscles Deformities of the spine, such as: Scoliosis (curvature of the spine), Kyphosis ( thoracic hump), tethered spinal cord syndrome Myalgia (muscle pain) and arthralgia [fmcpaware.org]

    Migraines and headaches, including postural headaches from spontaneous intracranial hypontension Fibromyalgia symptoms: Myalgia and arthralgia Other, less common signs and complications may include: Osteopenia (low bone density) Talipes equinovarus (club [medicalmarijuana.com]

    Correspondence to: R Grahame rodney.grahame{at}uclh.nhs.uk Joint hypermobility syndrome (JHS), previously known as benign joint hypermobility syndrome (BJHS), is a heritable disorder of connective tissue that comprises symptomatic hypermobility predisposing to arthralgia [doi.org]

The clinical evaluation and family history are important diagnostic tools. The qualitative and quantitative analysis, sequencing and biochemical testing can establish the type of Ehlers Danlos syndrome present in the patients. Deletion and duplication testing can also be done to pinpoint the mutations that have occurred. Prenatal diagnosis pre implantation genetic diagnosis (PGD) for at-risk pregnancies can also be done.

  • Platelet Aggregation Abnormal

    ROTEM ), platelet aggregation abnormalities can be expected in about 26% of patients [[ 21 ]]. New measures of platelet function such as PFA-100 or Multiplate show normal values and should not be used routinely. [ncbi.nlm.nih.gov]

    ROTEM ), platelet aggregation abnormalities can be expected in about 26% of patients [[21]]. New measures of platelet function such as PFA-100 or Multiplate show normal values and should not be used routinely. [ojrd.biomedcentral.com]

Conservative treatment of Ehlers Danlos syndrome is possible with the following:

Symptomatic treatment of bone, gastrointestinal, dental, and hematologic manifestation should be done accordingly [9] [10].

The surgical treatment is delayed in favor of physiotherapy for as long as possible. Long-term improvement in shoulder stability with Achilles tendon allograft reconstruction of the joint capsule has been reported.

The prognosis is poor for the patients suffering from the vascular variety of Ehlers Danlos syndrome. Complications leading to morbidity and sudden death are often seen.

Prognosis is better for the other types of Ehlers Danlos syndrome, although there is reduced quality of life.

Based on the clinical and molecular patterns, Ehlers Danlos syndrome has been subdivided into six clinical forms.

Classical

Genes other than those coding for collagen have been hypothesized to be involved in the classical type of Ehlers Danlos syndrome. In 30 to 50% of these cases, mutations in the genes COL5A1 AND COL5A2 that encode type V collagen have been observed [4] [5]. It is autosomal dominant.

Hypermobility

It is also an autosomal dominant disorder. The gene involved in its causation has not been detected as yet.

Vascular

An autosomal dominant disorder, the vascular type arises due to the mutations in COL31A gene encoding the type III collagen [6].

Kyphoscoliosis

Inherited as an autosomal recessive trait, kyphoscoliosis type arises due to the mutations in the genes encoding lysyl hydroxylase, an enzyme responsible for hydroxylation of lysine residues during collagen synthesis.

Arthrochalasia

Having an autosomal dominant pattern of inheritance, the arthrochalasia variant of Ehlers Danlos syndrome arises due to the mutations in COL1A1 or COL1A2 genes, resulting in formation of structurally abnormal pro α 1 or pro α 2 chains that resist cleavage of N-terminal peptides, a crucial step in type I collagen synthesis.

Dermatosparaxis

It is an autosomal recessive disorder, caused by defect in the conversion of procollagen to collagen.

Being a genetic disorder, the incidence of Ehlers Danlos syndromes, worldwide is 1:5,000 people worldwide. The hypermobility and classical variants are more common. Hypermobility Ehlers Danlos syndrome affects 1 in 10,000 to 15,000 while classical type occurs in as many as 1 in 20,000 to 40,000 people worldwide. Other forms of Ehlers Danlos syndrome are even rarer.

The disease is equally prevalent in all races. Ehlers Danlos syndrome is inherited in autosomal pattern [7]. It occurs without the involvement of sex chromosomes, therefore both sexes are equally affected. Although present at birth, it becomes apparent much later.

Median life expectancy for patients with vascular type Ehlers Danlos syndrome is 50 years. Average life span of patients with Ehlers Danlos syndrome is 50 years. Only the spontaneous rupturing of vessels and intestines can pose life threatening risks. Uterine rupture during pregnancy can also endanger maternal and neonatal life.

Collagen is an integral part of the connective tissue. Faulty synthesis and functioning can give rise to hyperextensibility of the skin. As a result, grotesque deformities arise. Joint dislocations become common. Skin becomes lax and prone to injuries.

Collagen deficiency in arterial wall causes thinning of vascular walls which can rupture spontaneously. Being a part of scar tissue, fault in the laying down of scars after injury can lead to delayed wound healing and easy bruising even after minor injuries.

Type I collagen is present in muscles. Its deficiency leads to impairment of motor functions and difficulty in starting and carrying out the movements (hypotonia). Cramps, easy fatigability and malaise ensue. Being part of the connective tissue of the valves, deficient and faulty collagen can also lead to dysfunction of the valves.

The vitreous humor of eye also contains collagen, the deficiency of which can lead to visual disturbances. Being part of the bone and cartilage, deficiency of collagen also induces bony deformities like scoliosis.

Constant surveillance of at risk population with family history of Ehlers Danlos syndrome should be done as a primary preventive measure. Resistance exercise can increase muscle tone. High impact activities should be avoided. Crutches, canes, and walkers should be used but with caution, as they tend to exert pressure on the upper extremities.

Secondary interventions, like calcium and vitamin D supplementation should also be done.

Ehlers Danlos syndromes are a genetically inherited, heterogeneous group of disorders that arise due to abnormality of collagen fibers [1]. There are several different types of Ehlers Danlos syndrome depending upon the type of the abnormality [2][3]. The abnormality may arise in the structure or synthesis of collagen or in the proteins that closely interact with collagen. The defect may also arise in one of the proteins closely associated with collagen, like those taking part in its post transcriptional modification.

Collagen provides basic structural support to the connective tissue and is found in tendons, ligaments, vascular wall, cornea, cartilage, bone, gut, muscles and in the skin in abundance. Therefore, the changes in the structure and functions of collagen can lead to the manifestation of a wide range of clinical symptoms.

Ehlers Danlos syndrome is a syndrome in which anomalies arise in skin and other soft tissues of the body. The basic fault lies in the genetic makeup of the individual therefore, Ehlers Danlos syndrome tends to run in families.

As basic structural support of organs is lost in Ehlers Danlos syndrome, therefore, patient experiences signs such as thin and fragile skin, ability to bend the joints to degrees that are not normally possible, easy dislocation of joints, easy bruising even after minor injuries, bursting of blood vessels, difficulty in starting and maintaining movements, easy fatigability and delayed wound healing.

  1. Patel AB, Renge RL. Ehler-Danlos syndrome. Indian pediatrics. Aug 2002;39(8):784-785.
  2. Parikh F, Sivaramakrishnan A, Pai-dhungat JV. Type VI Ehler Danlos Syndrome. The Journal of the Association of Physicians of India. Aug 2004;52:631.
  3. Ciarloni L, Perrigouard C, Lipsker D, Cribier B. [Ehler-Danlos syndrome type VIII]. Annales de dermatologie et de venereologie. Mar 2010;137(3):194-197.
  4. Wenstrup RJ, Florer JB, Willing MC, et al. COL5A1 haploinsufficiency is a common molecular mechanism underlying the classical form of EDS. American journal of human genetics. Jun 2000;66(6):1766-1776.
  5. Wenstrup RJ, Florer JB, Davidson JM, et al. Murine model of the Ehlers-Danlos syndrome. col5a1 haploinsufficiency disrupts collagen fibril assembly at multiple stages. The Journal of biological chemistry. May 5 2006;281(18):12888-12895.
  6. Eder J, Laccone F, Rohrbach M, et al. A new COL3A1 mutation in Ehlers-Danlos syndrome type IV. Experimental dermatology. Mar 2013;22(3):231-234.
  7. Araki T, Samejima T, Sako T. [Ehler-Danlos syndrome occurring in a family]. Seikeigeka. Orthopedic surgery. Oct 1966;17(10):822-826.
  8. Bathen T, Hangmann AB, Hoff M, Andersen LO, Rand-Hendriksen S. Multidisciplinary treatment of disability in ehlers-danlos syndrome hypermobility type/hypermobility syndrome: A pilot study using a combination of physical and cognitive-behavioral therapy on 12 women. American journal of medical genetics. Part A. Dec 2013;161A(12):3005-3011.
  9. Bergqvist D, Bjorck M, Wanhainen A. Treatment of vascular Ehlers-Danlos syndrome: a systematic review. Annals of surgery. Aug 2013;258(2):257-261.
  10. Jones ML. Orthodontic treatment in Ehlers-Danlos syndrome. British journal of orthodontics. Jul 1984;11(3):158-162.

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