Written by Santi Farghali
Edited by Anirudh Koneru
Published on 12/31/2020
Ehlers-Danlos syndromes (EDS) are a group of related genetic disorders caused by an inefficiency in the functioning of collagen within the body.
Click HERE to watch a video summarizing EDS.
There are approximately thirteen subtypes of EDS, which are characterized by subtle genetic differences between them. Some examples of these subtypes are cardiac-valvular, hypermobile EDS and brittle cornea syndrome.
The inheritance pattern of EDS is dependent on the subtype, and is either autosomal recessive or autosomal dominant. Other forms of this disease exist, but they are extremely rare and so few exist in literature that they are not very well understood.
The problems faced by patients with EDS can be due to one of two factors, both related to the normal functioning of collagen in the body. Collagen is a glycoprotein that serves many purposes in the body, specifically in providing structural support by binding together layers of cells and tissues in various locations in the body, especially the blood vessels, heart, skin, muscles, and joints, all of which are negatively impacted as a result of EDS.
The first issue encountered in EDS is that collagen in the body is very weak, and does not have the strength to perform its necessary functions. The second issue involves a lack of sufficient collagen, because production of this protein is very low. As a result of this ineffectiveness of collagen in the body, patients with EDS often experience complications involving the skin, muscles, bones, joints, and blood vessels.
The skin of EDS patients is often described as "loose" or "velvety" as a result of inefficient collagen, and they often face problems with healing wounds and often develop "paper-thin" scars. They also have a feature of hypermobility in joints that dislocate easily if not taken careful care of. In addition to experiencing frequent and easy bruising, fragile blood vessels, which is another characteristic of EDS, can increase the tendency to serious episodes of bleeding.
Signs and Symptoms:
Each Subtype has its own symptoms. Below are the signs and symptoms of the most common type of Ehlers-Danlos syndrome include:
Overly flexible joints: Because the related tissue that holds joints together is looser, the joints can move far past the conventional range of motion. Joint pain and dislocations are common.
Stretchy skin: Weakened related tissue allows the skin to stretch rather more than usual. A pinch of the skin can be pulled up off from the flesh, but it'll snap right into place after the person yields. The skin may also feel exceptionally soft and velvety.
Fragile skin: Damaged skin often doesn't heal well. For instance, the stitches closing a wound will often tear out and leave a gaping scar. These scars may look thin and crinkly.
Symptom severity can vary from person to person. For example, some people with Ehlers-Danlos syndrome will have overly flexible joints, but few or none of the skin symptoms.
Hypermobile EDS:
People with hEDS may experience:
Joint hypermobility
Loose, unstable joints that dislocate easily
Joint pain and clicking joints
Extreme tiredness (fatigue)
Skin that bruises easily
Digestive problems, like heartburn and constipation
Dizziness and an increased pulse rate after standing up
Problems with internal organs, like bicuspid valve prolapse or organ prolapse
Problems with bladder control (stress incontinence)
In recent times the term “hypermobile EDS” is defined more strictly, with many forms of EDS now classified on a hypermobility spectrum.
Classical EDS:
Classical EDS (cEDS) is less frequent than hypermobile EDS and tends to affect the skin more.
People with cEDS may experience:
Joint hypermobility
Loose, unstable joints that dislocate easily
Stretchy skin
Fragile skin that may split easily, especially over the forehead, knees, shins, and elbows
Smooth, velvety skin that bruises easily
Slow-healing wounds that leave wide scars
Hernias and organ prolapse
Vascular EDS:
Vascular EDS (vEDS) is a rare form of EDS and is considered to be the most serious.
It affects the internal organs, especially blood vessels, causing them to open much wider than is considered normal. As a result, life-threatening bleeding takes place.
People with vEDS may experience:
Skin that bruises very easily
Visible small blood vessels within thin skin, especially on the upper chest and legs
Fragile blood vessels that will tear or bulge, leading to significant internal bleeding
Organ problems risk such as the bowel tearing, the womb tearing (in late pregnancy), and the lungs are partially collapsing
Hypermobile toes and fingers, unusual appearances (such as a skinny nose and lips, large eyes and tiny earlobes), varicose veins, and delayed wound healing
Kyphoscoliotic EDS:
Kyphoscoliotic EDS (kEDS) is another rare form of EDS.
People with kEDS may have:
Curvature of the spine – this starts in babyhood and infrequently gets worse within the teenage years
Joint hypermobility
Loose, unstable joints that dislocate easily
Weak muscular tonus from childhood (hypotonia) – this could cause a delay in sitting and walking, or difficulty walking if symptoms intensify
Fragile eyes which will easily be damaged
Soft, velvety skin that's stretchy, bruises easily and scars
Etiology:
Ehlers-Danlos syndromes (EDS) are genetic disorders that are caused by mutations in several different genes, including COL5A1, COL5A2, COL1A1, COL3A1, TNXB, PLOD1, COL1A2, FKBP14, and ADAMTS2.
Some families cannot determine the underlying genetic cause of the disease, which can be due to changes in the structure, production, or processing of collagen. As collagen provides structure and strength to connective tissues throughout the body, a defect in this protein by a mutation can weaken the related tissues inside the skin, bones, blood vessels, and organs. This results in the symptoms and signs of EDS.
Diagnosis:
A diagnosis of Ehlers-Danlos syndromes (EDS) is regularly supported by the presence of characteristic signs and symptoms. Family history of the disease is also important in supporting a diagnosis based on symptomatology alone. Depending on the subtype suspected, a number of the subsequent tests could also be ordered to support the diagnosis:
Collagen typing can be performed to diagnose EDS. On a skin biopsy, it is performed to help in the diagnosis of the dermatosparaxis type, vascular type, and arthrochalasia type. People with EDS often have abnormalities of certain forms of collagen.
Genetic testing is on the market for several subtypes of EDS; however, it's not an option for many families with the hypermobility type.
Imaging studies like CT scan, MRI, ultrasound, and angiography could also be useful in identifying definite features of the condition.
Urine tests to detect deficiencies in certain enzymes that are important for collagen formation could also help diagnose the kyphoscoliosis type.
Treatments/Therapies:
There is no medical therapy that can cure EDSs. The treatment of patients with EDSs primarily entails preventing, monitoring, and treating EDS-associated complications. Protecting the skin is an important step to prevent worsening of the condition, for which regular use of sunscreen and mild soaps is recommended. Vitamin C supplementation can assist with bruising, and physical therapy aims to prevent joint injuries by making the supporting muscles of these joints stronger.
However, because EDS patients have weak joints, it is recommended that they avoid strenuous physical activity that can lead to joint injuries, including high impact exercise, contact sports, and heavy lifting. Keeping blood pressure low is also an important therapeutic goal, because individuals with EDS have more fragile blood vessels, and high blood pressure has the potential to lead to serious internal bleeding.
Certain experimental therapies are available as well, including drugs such as Edsivo, aimed at treating vEDS by promoting collagen production in blood vessels, Excallagen, which is a topical therapy that aims to assist in wound healing, and Prolotherapy, which is a medication that is injected into the body to assist with joint development, particularly in hypermobile EDS.
For the facial plastic and reconstructive surgeon, the treatment of those patients should be individualized supported by the patient’s chief concern, manifestations, and subtype of EDS. Herein, doctors and scientists discuss recommendations within the treatment of patients with EDSs for facial plastic surgeons.
There are also ring splits, that resemble rings, to help manage hypermobility in fingers.
Prevention is not possible for this condition, but genetic counselling can be beneficial in allowing a couple to decide whether or not they wish to have a biological child.
Rarity:
Previous estimates report EDS at 1 in 5000 births, with classical and hypermobile EDS accounting for roughly 90% of cases. These estimates predate the newer diagnostic criteria, which might reduce the prevalence of hypermobile EDS considerably.
The prevalence of vascular EDS is estimated to be 1 in 90 000, and that of classical EDS is 1 in 20,000. Joint hypermobility is common and hypothetically occurs in 10-30% of the population worldwide.
Resources for patients and caregivers:
Organizations:
Facebook Groups:
There are currently two clinical trials studying Ehlers-Danlos Syndrome that are recruiting participants.
The first, Evaluation of the Effect of Custom Compression Garments on Standing Static Balance on Ehlers Danlos Syndrome, is located in France.
For more information on this study, click here.
The other study, Validity of Somatosensori Remediation for Postural Control in the Treatment of Ehlers-Danlos Syndrome Hypermobility Type, is also located in France, and is testing the effectiveness of compressive garments and somatosensori remediation for EDS.
For more information on this study, click here.
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References:
GARD Genetic and Rare Disease Information Center. (2017, April 20). Ehlers-Danlos syndromes. GARD. https://rarediseases.info.nih.gov/diseases/6322/ehlers-danlos-syndromes
National Organization For Rare Disorders. (n.d.). Ehlers Danlos Syndromes. NORD. Retrieved September 4, 2020, from https://rarediseases.org/rare-diseases/ehlers-danlos-syndrome/
Mayo Clinic Staff. (2017, October 13). Mayo Clinic. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/ehlers-danlos-syndrome/symptoms-causes/syc-20362125
Ghali, N., Sobey, G., & Burrows, N. (2019). Ehlers-Danlos syndromes. BMJ, 366, l4966, From https://www.bmj.com/content/366/bmj.l4966
Joseph, A. W., Joseph, S. S., Francomano, C. A., & Kontis, T. C. (2018). Characteristics, diagnosis, and management of Ehlers-Danlos syndromes: A review. JAMA facial plastic surgery, 20(1), 70-75. From https://jamanetwork.com/journals/jamafacialplasticsurgery/article-abstract/2660015
NHS. (2019, February 6). Ehlers-Danlos syndromes. https://www.nhs.uk/conditions/ehlers-danlos-syndromes/
SilverRing™ Splint Company. (2019, September 13). Ehlers-Danlos Syndrome - EDS: Connective tissue disorder causing joint hypermobility. Retrieved December 31, 2020, from https://www.silverringsplint.com/problems-addressed/eds/
XpertDox. (2018, Oct 02). What is Ehlers Danlos Syndrome?. YouTube. https://www.youtube.com/watch?v=cPpl2cxjBuA
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