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The Ehlers-Danlos syndromes (EDS) are a group of hereditary disorders of connective tissue that are varied in the ways they affect the body and in their genetic causes. The underlying concern is the abnormal structure or function of collagen and certain allied connective tissue proteins.
They are generally characterized by joint hypermobility (joints that move further than normal range), joint instability (subluxation [partial separation of the articulating surfaces of a joint]) and dislocations (full separation of the surfaces of a joint), scoliosis, and other joint deformities, skin hyperextensibility (skin that can be stretched further than normal) and abnormal scarring, and other structural weakness such as hernias and organ prolapse through the pelvic floor. In the rarer types of EDS, there is also weakness of specific tissues that can lead, for example, to major gum and dental disease, eye disease, cardiac valve and aortic root disorders, and life-threatening abdominal organ, uterine, or blood vessel rupture.
The Ehlers-Danlos syndromes are currently classified into thirteen types. In all but the hypermobile subtype (hEDS) genetics variants have been identified as the cause for the disorder and are part of the diagnostic criteria. Since the publication of the 2017 criteria for EDS a couple of other genes have been identified describing additional new types. In particular, these include AEBP1-related EDS, and a COL1A1/A2 gene variant causing overlap between EDS and Osteogenesis Imperfecta.
Each EDS type has a set of clinical criteria that help guide diagnosis; a patient’s physical signs and symptoms can be matched up to the major and minor criteria to identify the type that is the most complete fit. That said, there can be substantial overlap between the EDS types.
Sometimes a “provisional clinical diagnosis” of an EDS type is made. This can occur when a person meets a minimal clinical requirement but has no access to molecular confirmation or whose genetic testing shows one or more gene variants of uncertain significance. These individuals should be followed clinically, and alternative diagnoses and expanded molecular testing, skin histology (microscope examination of a skin biopsy), and testing of possibly affected family members should be considered.
Please remember that an individual’s experience with EDS is their own and may not necessarily be the same as another person’s experience. Diagnostic criteria are meant solely to distinguish an EDS from other hereditary disorders of connective tissue, and there are many more symptoms for each EDS than there are in the diagnostic criteria. What are the signs and symptoms of Ehlers-Danlos syndromes?
Pain and fatigue are almost universal in the Ehlers-Danlos syndromes. Clinical manifestations of an EDS are typically joint and skin related and may include:
Joints
Joint pain (arthralgia) and deformity; muscle pain (myalgia), and nerve pain (neuralgia); loose/unstable joints which are prone to frequent dislocations and/or subluxations and injury; muscle tension and weakness; weakness of the voice box and larynx; hernias; pelvic floor weakness and prolapses of the rectum, bladder or vaginal wall and uterus; and nerve disorders (neuropathy) from cord and nerve entrapment or sensory nerve damage.
Skin
Soft velvety-like skin; variable skin hyper-extensibility; fragile skin that tears or bruises easily (bruising may be severe including clots under the skin (hematoma)); severe scarring; slow and poor wound healing; development of molluscoid pseudo tumours (fleshy lesions associated with scars over pressure areas).
Less Common
Arterial/intestinal/uterine fragility or rupture (usually associated with the vascular type of EDS, vEDS); scoliosis at birth and scleral fragility (associated with the Kyphoscoliotic Type, kEDS); congenital hip dislocations; poor muscle tone; and severe gum disease.
Co-morbidities
Several disorders are associated with EDS and in particular the hypermobile variant (hEDS). Among the most common of these are upper and lower gastrointestinal tract complications such as swallow difficulties and sluggish stomach and large bowel, causing nausea, vomiting, acid reflux, bloating, pain, and absorption and food intolerance concerns; autonomic disturbances of heart rate and blood pressure, bowel and bladder function, and temperature regulation; anxiety, depression, and phobias; and organ / systemic inflammation related to mast cell activation.
What causes Ehlers-Danlos syndrome?
Connective tissue is everywhere in the body. It provides support and structure to other tissues and organs including bone, ligaments, tendons, blood vessels, lymphatic vessels, the tissue that holds the gastrointestinal tract in place, etc.
There are many proteins in connective tissue. One of the key proteins is collagen. In the Ehlers-Danlos syndromes, there are faults in the genes that determine how the body makes collagen, and/or in some subtypes other proteins that work alongside collagen. This leads to the connective tissue becoming weaker. Different tissues and organs can be affected in diverse ways depending on the genetic fault. This explains why there are several subtypes of EDS.
The genetic basis for hypermobile EDS (hEDS) is still unknown, so an hEDS diagnosis rests on the criteria and what your doctor finds during your examination.
How prevalent are Ehlers-Danlos syndromes?
The overall prevalence of the Ehlers-Danlos syndromes is between 1 in 3,500 to 1 in 5,000 people. The hypermobile variant (hEDS) is by far the most common type and may be more common than that as it may be missed or misdiagnosed as something else.
Most are rare e.g., 1 in 40,000 – 200,000 and some are ultrarare i.e., less than 1 in a million people. Individuals of all racial and ethnic backgrounds are affected by EDS which can present with complications from birth and progress over time.
How are Ehlers-Danlos syndromes inherited?
The two known inheritance patterns for the Ehlers-Danlos syndromes are autosomal dominant and autosomal recessive.
What is hypermobility spectrum disorder (HSD)?
Some people have joint hypermobility, joint instability, injury, and pain in their joints and muscles that is identical in its mechanism to that seen in EDS. However, they do not have other connective tissue problems like those described above (skin, gums, bowel, and blood vessel rupture, etc) and therefore do not have signs of EDS or any other of the hypermobility-related disorders of connective tissue such as Marfan syndrome or Loeys-Dietz syndrome, etc. In this situation where there is no other explanation for hypermobility, instability, and joint and muscle injury, the term hypermobility spectrum disorder (HSD) is used.
Like EDS, HSD is associated with several co-morbidities. Among the most common of these are nausea, vomiting, acid reflux, bloating, pain, and absorption and food intolerance concerns; autonomic disturbances of heart rate and blood pressure, bowel and bladder function, and temperature regulation; anxiety, depression, and phobias; and organ / systemic inflammation related to mast cell activation.
The prevalence of HSD may be in the order of 1 in 500 to 1 in 600 based on a large population study of medical records. HSD may be more common than that as it may be missed or misdiagnosed as something else.
How is an EDS or HSD diagnosed?
If you think you might have one of the Ehlers-Danlos syndromes or hypermobility spectrum disorders, and particularly if someone in your immediate family has been diagnosed, ask your doctor if a diagnosis fits your symptoms. If they choose to, any doctor who can diagnose a disease is able to diagnose EDS and HSD, but it is more likely that you will be given a referral to a specialist in a discipline such as Rheumatology or Clinical Geneticist: someone adept at distinguishing between these diseases, and able to do the testing necessary to differentiate EDS and HSD from the more than 200 other heritable connective tissue disorders.
A diagnosis is important because, although EDS and HSD are not curable, they are treatable. Knowing the type of EDS or HSD gives you and your medical team some idea of where problems might come from and why they are happening. And as more people are diagnosed, EDS and HSD gain the attention needed to increase care provision, education, research into these conditions leading to better health outcomes.
Your path to an EDS or HSD diagnosis starts with the doctor taking a full history of your concerns and then a physical examination that should look at your joints, skin, and any other parts of the body that might be affected. Your family medical history may also hold valuable information.
Diagnosis of an EDS subtype comes by finding the one that most matches your symptoms and the diagnostic criteria. Your signs and symptoms will be matched up to the major and minor criteria to identify the subtype that is the most complete fit. There is substantial symptom overlap between the EDS subtypes and the other connective tissue disorders including HSD, as well as a lot of variability between them. So, a definitive diagnosis for all the EDS subtypes—except for hypermobile EDS (hEDS)—also calls for confirmation by gene testing to identify the responsible variant for the gene affected in each subtype.
What is the prognosis of someone with an Ehlers-Danlos Syndrome?
While there is no cure for the Ehlers-Danlos syndromes, there is treatment for symptoms, and there are preventative measures that are helpful for most.
There can be a wide range of severity of symptoms and concerns within a family, and each person’s case of Ehlers-Danlos syndrome will be unique. The prognosis depends on the type of Ehlers-Danlos syndrome and the individual. Organ and vessel rupture can lead to early death in those with vascular EDS (vEDS), and some other rare types of EDS. Severe restriction of breathing due to marked scoliosis for example may increase the risk of lung disease and reduce life expectancy. In some cases, gastrointestinal failure may lead to other organ failure and death. However, for most people the life expectancy is normal.
For some people, their concerns worsen over time, for example, joint pain and instability leading to reduced function and quality of life. This might occur because they have not received the right advice, or treatments have not been effective, or treatments have only been able to slow down a natural tendency in that person for their condition to worsen.
For other people, treatment can significantly improve their well-being, function, and quality of life, or hold them in a steady state so that they no longer feel they are deteriorating and are able to better manage their concerns.
Taken from: ehlers-danlos.com |
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Swindon Group - Annie: 0208 736 5604
Helpline: 0800 907 8518
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