What is Ehlers-Danlos Syndrome?
Ehlers Danlos syndrome (EDS) is a group of inherited disorders related to connective tissue, the material that provides structure and support to our skin, joints and blood vessels. People with EDS experience very flexible skin, joints that can move beyond the normal range, easy bruising, and blood vessels that are easily broken. The condition is diagnosed mostly through physical examination, but a genetic test may also be performed to identify the specific type of EDS a person has by looking for changes in the genes responsible for collagen production. Collagen is a protein that gives our skin, bones, and connective tissues strength and elasticity.
In 2017, scientists proposed a classification system that recognizes 13 different forms of EDS. This is a complex condition with many variations, each caused by different changes at the genetic level influencing collagen production. Some of the different types of EDS include the classical, vascular, hypermobile, arthrochalasis, kyphoscoliotic, and dermatosparaxis types.
People with EDS may not always show symptoms. However, common signs include extra-flexible joints (known as joint hypermobility), pain that lasts a long time, problems with the autonomic nervous system (the part of the nervous system responsible for controlling bodily functions like heart rate and digestion), stomach and bowel problems, oversensitive immune responses, and issues with anxiety or fear.
It’s important for doctors to recognize the specific type of EDS a person has because each type can have different health issues. For instance, people with the vascular type of EDS have a bigger risk of arteries or organs bursting or tearing, which can be life-threatening. Understanding these risks can help guide proper medical care and advice for patients with this condition.
What Causes Ehlers-Danlos Syndrome?
Ehlers-Danlos syndrome, or EDS, is a group of inherited disorders that affect collagen and extracellular matrix protein (proteins that provide support to the surrounding cells). These disorders can present in different ways, making EDS quite diverse.
EDS is often passed down from parents to their children. However, in half of the cases, patients might have a new mutation – meaning they might be the first in their family with the disorder.
Researchers have used various methods to categorize EDS over the years. The system used was updated in 1997 and is called the Villefranche classification. But in 2017, the International EDS Consortium introduced a new system because the ways EDS can present tend to overlap and are quite diverse.
13 different types are covered in the 2017 classification. However, we’ll focus on the top five most important based on how often they occur and their causes.
The first type, Classical EDS, comes from either the COL5A1 or COL1A1 genes, which are responsible for making type V and Type I collagen, respectively. It generally presents with thin and fragile skin that heals poorly, overly flexible joints, and other signs like easy bruising, hernias, and small, hard, movable lumps under the skin.
Classical-like EDS is a result of mutations in the TNXB gene. This type doesn’t result in poor healing but has similar symptoms to Classical EDS, such as overly flexible skin and joints, and easy bruising. Additional symptoms can include swelling in the legs, muscle weakness, hand and foot muscle shrinkage, nerve disorders in the limbs, foot deformities, and organ prolapse (when organs like the uterus, vagina, or rectum drop down or slip out of place).
Cardiac-valvular EDS implicates mutations in COL1A2 and/or NMD genes. It shares the same symptoms as the previous two types, but it is also associated with progressive problems with the heart valves. Additionally, this type can lead to foot deformities, chest wall deformities, joint dislocations, and hernias around the groin.
Vascular EDS stems from mutations in the COL3A1 and/or COL1A1 genes. It’s associated with a high risk of severe complications like early artery rupture, uterine rupture during the third trimester of pregnancy, and the formation of an abnormal connection between the arteries and spaces in the skull without trauma. People with this type may also have a higher likelihood of hip dislocation at birth and spontaneous collapse of the lung.
Hypermobile EDS is diagnosed based on clinical symptoms only. Researchers haven’t identified any specific genetic mutation associated with this EDS type as of the 2017 classification system. This type’s diagnosis relies on meeting three strict criteria.
Risk Factors and Frequency for Ehlers-Danlos Syndrome
Ehlers-Danlos syndrome (EDS), a condition that affects connective tissues, has varying prevalence rates depending upon the specific subtype of the syndrome. Estimates suggest that it might affect anywhere between one in 5,000 to one in 100,000 people, but this likely falls short of the actual numbers. The exact prevalence of the different EDS subtypes is still unclear. Recent literature reviews haven’t been hugely helpful due to changes in how the syndrome is classified and diagnosed.
- The hypermobility type of EDS is the most common, affecting between one in 10,000 and one in 15,000 people.
- The classical type is also fairly common, affecting somewhere between one in 10,000 to one in 20,000 people.
- Other EDS subtypes are extremely rare. For example, the EDS kyphoscoliotic type has been identified in only about 60 people worldwide, and the EDS dysfibronectinemic type is known to only affect one single family.
It’s crucial to remember that these numbers may not reflect the true prevalence of EDS. This is because milder cases of EDS, where joint or skin symptoms are minimal, may not be clinically significant or may not seek medical attention. Even if they do, diagnosing EDS can be challenging due to the subtlety of signs and symptoms, and genetic testing is not always indicated or pursued.
Signs and Symptoms of Ehlers-Danlos Syndrome
Ehlers-Danlos Syndrome (EDS) is a condition that affects the body’s connective tissues, such as skin and joints. It’s there from birth because it’s in the body’s collagen, but it often isn’t noticeable right away. People presenting with EDS often have particularly stretchy skin and hyperflexible joints.
Skin symptoms are the main signs of EDS, and they can include increased stretchiness, smooth and soft texture, weak skin, slow wound healing, and thin, atrophic scars after wounds have healed. Often, a dislocated shoulder is the first sign of EDS. This variety of skin features helps doctors diagnose EDS.
Children with EDS may have a range of symptoms:
- Issues with regulating the body’s responses (orthostatic intolerance)
- Diarrhea
- Unintentional urination
- Balance problems
- Pain
- Fatigue
- Issues with muscle strength leading to falls and sometimes difficulty in walking
Despite these physical challenges, mental development is normally unaffected.
People with EDS can also have dental issues, such as missing permanent teeth, late tooth growth, and abnormal tooth structure. Even a lack of gum tissue could be a feature of EDS. So, regular dental check-ups can be vital for people with EDS.
The excessive flexibility in EDS patients leads to frequent joint dislocations, early onset of arthritis, and chronic pain. At birth, a baby might have hip dislocations. Patients may also experience recurring fractures.
EDS also affects the body’s internal organs, making them susceptible to spontaneous and trauma-induced ruptures. Another common symptom is the occurrence of hernias and rectal prolapse.
On physical examination, the skin of EDS patients often appears white and soft, showing underlying blood vessels easily. The skin feels doughy and stretches easily, but returns to its original position instantly. Small, spongy outgrowths (Molluscoid pseudotumors) could be seen on scars and pressure points, particularly in patients with Type I EDS.
Under the skin, small, deep nodules can often be felt. These nodules could be seen in the arms and over the tibia, and a radiography may show calcification. The skin is often fragile, with frequent bruises and cuts. The joints are overly flexible, but this can vary from person to person. This excessive joint movement is most common in the fingers, but all joints can be affected.
Testing for Ehlers-Danlos Syndrome
If a doctor believes that a patient may have Ehlers-Danlos syndrome, or EDS, they will generally make their diagnosis based on a collection of symptoms. They will look at any specific complaints the patient has, and they will examine those areas of the body to see if the issues align with EDS. From there, they will try to figure out how much of the body is affected by the syndrome.
A common approach for diagnosing the classical type of EDS involves a thorough examination of the skin. They might also check the patient’s ability to flex their joints beyond the normal range, which is known as the Beighton criteria. For infants and children, their motor development may need to be assessed. Doctors can also recommend a baseline heart ultrasound for kids under age 10. Lastly, if the patient bruises easily, doctors will check their clotting factors to see if they have another bleeding disorder.
Testing for the syndrome is done by stretching the skin to see if it immediately reverts back to normal when released. This helps differentiate EDS from other conditions that cause the skin to be loose.
If EDS is in the picture, doctors can use CT scans, MRI scans, and echocardiography (heart ultrasounds) to see if the patient has any heart problems commonly found in EDS patients, such as mitral valve prolapse or aortic dilatation. These tests can also check for appearances of white spots in the brain that are associated with the condition.
Although blood work doesn’t usually assist in diagnosing EDS, in some cases specialized lab tests can be beneficial. It should be noted, however, that patients showing signs of easy bruising and bleeding often have normal bleeding times and coagulation studies, unless there’s another underlying disorder at play.
Eventually, for an accurate diagnosis, the doctor may refer the patient to a genetic specialist who can conduct genetic tests. A tissue biopsy can also be performed, where an electron microscope is used to look for abnormalities in the collagen (a protein that strong fibers for the skin, tendons, ligaments and many other parts in the body), although this technique isn’t used regularly. Further evaluations are based on the patient’s symptoms. For example, if a patient complaining of pre-fainting and has a negative cardiovascular test result, a tilt table test may be done to check for related disorders like postural orthostatic tachycardia syndrome (POTS) or other dysautonomia (a diseases or malfunctions affecting the autonomic nervous system).
Extra care is needed for patients with EDS who’ve experienced trauma as they have a higher risk of joint dislocation and vessel and organ rupture. It’s important to bear in mind that symptoms may be more severe than the trauma would suggest, especially in young patients. It’s also crucial to rule out any non-accidental injuries.
Treatment Options for Ehlers-Danlos Syndrome
If you have Ehlers-Danlos syndrome (EDS), your medical team should be well-aware of the many complications your condition may cause, as well as ways to help prevent these issues. EDS doesn’t have a cure – so, the focus of treatment is on stopping the disease from getting worse and avoiding complications.
When it comes to managing your EDS, your treatment will involve a team of specialists. Each expert will address specific issues related to the parts of your body most affected by EDS. For example, if you have heart problems, you’ll see a cardiologist (a doctor specializing in heart health). If EDS is causing issues with your muscles and bones, an orthopedist (a specialist in the skeletal system) will monitor and treat those concerns. A geneticist or a family medicine provider might act as your main doctor and refer you to specialists based on your specific needs.
Because EDS affects your body’s collagen – the protein that gives structure to your skin, bones, and other tissues – it becomes difficult for your skin to heal wounds, as they may break open (a complication known as dehiscence). To limit this risk, whenever you have a cut or surgical incision, it’s essential that wound repair is done very carefully. This preservation process may include using deep closures (stitches that close multiple layers of tissue together), and keeping the stitches in place significantly longer than usual.
EDS can also cause your joints to be hypermobile – meaning they move beyond their normal range. This puts you at a higher risk of joint subluxation (partial dislocation) and dislocation. Since each injury raises your risk of more recurrences and complications – like osteoarthritis (a type of joint disease) – prevention is vital. Your medical team may advise you against high-risk activities like contact sports or weightlifting, to prevent injures to your joints.
Because EDS can make your blood vessels fragile, it’s important to routinely check your cardiovascular health. High blood pressure, for instance, places extra pressure on your delicate blood vessels and can cause complications over time. Regular screening for issues like aortic root and mitral valve abnormalities using echocardiography (a type of ultrasound for your heart) is essential. Depending on the results, you may need surgery to prevent complications like ruptures or congestive heart failure (a condition where your heart doesn’t pump blood as well as it should).
If you’re pregnant and have EDS, your care should be provided by obstetricians trained in managing high-risk pregnancies. They will guide you through any potential complications and ensure that you receive appropriate care.
What else can Ehlers-Danlos Syndrome be?
There are a few conditions that might get confused with Osteogenesis imperfecta (OI) type I, such as certain subtypes of Ehlers-Danlos syndrome. These can be confusing as they both may cause harm even from minor injuries and result in highly flexible joints. But there are ways to tell these diseases apart. For instance, patients with OI type I often show signs like blue whites of the eyes, hearing problems, deformities of the skull bones, or imperfect tooth development. While both conditions might show blue whites of the eyes, they have different types of gene mutations. Also, certain varieties of OI are not even considered in the list of possible diagnoses.
Marfan syndrome is also often mistaken for Ehlers-Danlos syndrome, in particular the hypermobility subtype. The two share several common traits. Yet, clinically and genetically, these two conditions can be distinguished. Marfan syndrome is often linked to mutations in the fibrillin-1 gene. If a patient has flexible joints, a particular body shape (marfanoid habitus), eye lens displacement, and/or health problems with the root of the aorta, doctors might suspect either Marfan syndrome or Ehlers-Danlos syndrome. However, abnormalities in the aortic root generally do not increase in severity in adulthood, unlike what is often seen in Marfan syndrome. Also, elbow problems are typically not a concern, and the body shape seen in Marfan syndrome is often more pronounced. Furthermore, genetic tests can confirm Marfan syndrome by revealing a mutation in fibrillin 1, which is not found in Ehlers-Danlos syndrome.
Loeys-Deitz Syndrome can get mixed up with Ehlers-Danlos syndrome due to both conditions being inherited in a similar pattern and early diagnosis of problems with the aorta, in particular aneurysms. But there are three key characteristics, a split in the soft hanging part of the palate/birth defect in the roof of the mouth, widely spaced eyes, and aneurysms that can steer the diagnosis towards Loeys-Deitz Syndrome. Unlike in some types of Ehlers-Danlos syndrome, these aneurysms can be found throughout the arteries and not just around the aortic root.
Cutis laxa might be confused with Ehlers-Danlos Syndrome at first glance. The skin occurrences in these two conditions can help tell the two apart. Although many people with Ehlers-Danlos Syndrome have notably stretchy skin, their skin returns to normal almost immediately after being stretched or touched. However, in individuals with cutis laxa, the skin takes longer to return to its original shape. Both conditions often show overlap in the form of heart valve involvement, vascular issues, and hernia development. In individuals with cutis laxa, genetic tests usually show mutations in the fibulin-5 gene.
Patient’s with Ehlers-Danlos Syndrome, particularly those with the hypermobility type, can often be misdiagnosed with fibromyalgia, chronic fatigue syndrome, or depression due to similar symptoms and the effect these conditions can have on a patient’s mental wellbeing. It’s important that doctors consider Ehlers-Danlos Syndrome as a possible diagnosis, because failing to spot it could lead to complications associated with the condition.
What to expect with Ehlers-Danlos Syndrome
The outlook of the condition Ehlers-Danlos syndrome varies significantly and is largely determined by the specific subtype and whether the patient is dealing more with living with the condition (morbidity) or the impact on their lifespan (mortality). The patient’s environment and disease subtype can strongly influence their morbidity, or the day-to-day effects of living with the disease.
For instance, if someone has the hypermobile type of Ehlers-Danlos syndrome and they learn about their condition early and avoid potentially harmful activities such as weightlifting, they might be able to manage their disease quite effectively throughout their life. However, when a patient experiences physical trauma causing repeated joint injuries, the disease can result in significant complications and may even necessitate surgical intervention.
When it comes to life expectancy or mortality, the hypermobile and classic subtypes of Ehlers-Danlos syndrome generally don’t impact it. However, the lifespan of patients with vascular and kyphoscoliotic subtypes is significantly affected. It is common for patients with the vascular subtype to have a major vascular (related to the veins and arteries) event by age 40 and a median lifespan of 48 years. Likewise, patients with the kyphoscoliotic subtype can experience issues with circulation or severe lung disease, both of which are known to decrease life expectancy.
It’s also important to note the psychosocial (psychological and social) impact of Ehlers-Danlos syndrome. Due to the absence of a cure and what can seem like unsuccessful treatments, patients may lose confidence in their healthcare providers. This might lead some patients to avoid seeking the healthcare they need as their condition progresses. Even though treatments (like beta-blockers for vascular protection) may have the intended medical outcome, these treatments might not make a patient feel better in their everyday life. Moreover, despite following the treatment recommendations, serious outcomes such as vascular injury might still occur.
Just like any chronic condition, Ehlers-Danlos syndrome can have considerable psychological and social implications, not only because of the symptoms and consequences of the disease itself, but also due to the limitations on activities that doctors might suggest to reduce risk to the patient. Furthermore, patients also report feeling unsupported by their healthcare providers, especially when reported symptoms don’t match visible or documented medical conditions.
Possible Complications When Diagnosed with Ehlers-Danlos Syndrome
One of the major concerns with Ehlers-Danlos Syndrome (EDS) is the risk of vascular and organ rupture, which can be life-threatening. These issues are most prevalent in certain subtypes of EDS but can occur in all forms. Vascular rupture, or the bursting of blood vessels, can happen in any part of the arterial system, but particularly in the chest and stomach. Organ rupture often happens in the uterus during pregnancy, in the colon, spleen, and liver. Patients should seek immediate medical attention if they experience sudden pain, even if there’s no obvious incident leading to the pain.
Patients with EDS may also have mitral valve prolapse, a heart valve disorder that can occur with or without regurgitation, or the backward flow of blood. The severity of this condition can range from mild to severe; in the more serious cases it can cause congestive heart failure and fluid buildup in the lungs.
Due to abnormalities in connective tissue, EDS patients face increased risks during childbirth. These include a higher chance of cervical incompetence, where the cervix is not strong enough to stay closed during a full-term pregnancy, and an increased risk of labour progressing prematurely. Vaginal childbirth is associated with a higher occurrence of significant vaginal and perineal tearing, which can lead to complications and even fatal outcomes. Pregnant EDS patients may also experience premature rupture of membranes, abnormal fetal positioning, prolapse of the uterus and bladder, and rupture of the uterus and major blood vessels.
People with EDS are more likely to bleed because of fragile blood vessels. This risk increases during pregnancy. If pre-existing conditions like mitral valve prolapse and aortic dilation are known, these conditions should be monitored closely during pregnancy.
Please note that any necessary surgical procedures, including those for avoiding life-threatening EDS complications, could lead to complications. This is due to the fragility of the blood vessels and organs. Healing times might be longer for EDS patients than for others, and there’s an increased risk of bleeding.
Feeling dizzy or faint when standing up (orthostatic intolerance) could signal a vessel injury, indicating potential blood loss. Though, this symptom in EDS patients, particularly those with the hypermobile type, could also indicate other issues like low blood pressure or Postural Orthostatic Tachycardia Syndrome (POTS). People with POTS, a disorder of the cardiovascular system, often experience palpitations, dizziness, and fainting. Some triggers can be identified, like changes in body position or infections, but not all triggers are known.
Sudden difficulty in breathing in a patient with EDS should trigger an immediate medical evaluation for a collapsed lung.
Repeated joint injuries in EDS patients can lead to early arthritis and the need for multiple orthopedic surgeries. The risk for this is especially high in the hypermobile and classical subtypes of EDS, as the connective tissue’s flexibility increases over time, thereby predisposing to more injury.
Sleep disturbances and sleep-disordered breathing, known as genetic obstructive sleep apnea (OSA), are linked with EDS. The cause for this link is believed to be due to abnormalities in the craniofacial soft tissues, often leading to long-term fatigue. A referral to a sleep specialist is recommended for any EDS patient experiencing these symptoms.
Preventing Ehlers-Danlos Syndrome
Ehlers-Danlos syndrome is a genetic condition that affects many parts of the body. One of the most important things you should know about managing Ehlers-Danlos syndrome is how you can slow down its progression and what you can expect as you go through life. This includes making changes to your day-to-day habits and sticking to the treatments recommended by your doctor, which could include physical therapy and other medical interventions.
To reduce your chances of further harm to your body, it’s advisable to avoid activities that could potentially hurt you. Engaging in low-resistance activities can help minimize your risk of long-term musculoskeletal problems, or issues regarding the muscles and skeleton.
It’s also crucial that you understand the importance of taking your medicines as recommended by your doctor, especially if they have prescribed beta-blockers or other drugs for high blood pressure. Adhering to this medication may improve your outlook regarding potential future vascular events, or events related to your blood vessels, possibly preventing serious issues like strokes.
