SPOTLIGHT ON EHLERS-DANLOS SYNDROME: SYMPTOMS, DIAGNOSIS, AND TREATMENT

Ehlers-Danlos syndrome (EDS) references a group of hereditary genetic disorders that affect the connective tissues of the body. Connective tissues provide strength and flexibility to the skin, bones, blood vessels, and other organs. People who have EDS usually have overly flexible joints, stretchy and fragile skin, and abnormal scar formation. These symptoms can vary from mild to severe depending on the type of EDS and the genes involved.^[1]

As a rare condition, EDS affects about 1 in 5000-100,000 people globally, depending on the type. The figures are thought to be higher due to a lack of general awareness of the condition that prevents proper diagnosis or leads to misdiagnosis.

This article aims to shine a spotlight on EDS, highlighting the types, symptoms, and causes, how to diagnose EDS, and the available EDS treatment options.

The Main Symptoms of Ehlers-Danlos Syndrome

Symptoms of EDS vary widely depending on the type and severity of the condition.

Joint hypermobility is one of the main defining features of the disease. This means that the joints can move far beyond the normal range of motion, leading to often painful symptoms. While this can affect any joint in the body, it is more common in the fingers, wrists, elbows, shoulders, hips, knees, and ankles. 

Other common EDS symptoms pertain to the skin and vascular system, which are classically elongated, weaker and prone to tearing in those with the condition. Weaker blood vessels typically impact other organs as well, causing tissue or organ fragility and a variety of generalized symptoms. The most commonly affected organs are the intestines, uterus, bladder, and lungs.

General EDS symptoms include:

• Joint stiffness, pain, swelling or dislocation
• Fragile skin that can extend beyond the normal range (skin hyperextensibility)
• Deformities
• Excessive bruising and scarring
• Skin rashes or conditions like eczema and dermatitis
• Unusually exposed veins through translucent skin
• Varicose veins
• Increased susceptibility to infections
• Headaches and migraines
• Tendency for bleeding
• Nosebleeds and bleeding gums
• Abdominal pain, bloating or gas
• Constipation and diarrhea
• Nausea and vomiting
• Shortness of breath and chest pain
• Coughing up blood
• Urinary incontinence
• Pelvic pain
• Menstrual irregularities

Complications

EDS is commonly associated with several other complications, including:

• Early onset arthritis
• Seizures
• Anxiety and depression
• Chronic pain and fatigue disorders
• Sleep disorders
• Pregnancy complications or infertility
• Nervous system disturbances, such as dysautonomia
• Issues pertaining to blood pressure, such as postural orthostatic tachycardia syndrome (POTS)
• Immune abnormalities such as severe allergies, exercise intolerance or mast cell activation syndrome
• Digestive complaints and sensitivities, including irritable bowel syndrome

Some EDS complications can be life-threatening, such as lung collapse or aortic dissection (in which the aorta tears and bleeds). Those with severe EDS need to live near well-equipped medical facilities and be monitored at all times in order to prevent mortality.

Ehlers-Danlos Syndrome Types

There are 13 subtypes of EDS, each with its own genetic cause and characteristic features.^[2] The three most common types of EDS include:

Hypermobile EDS (hEDS)

This is the most common type of EDS, affecting at least one in 5,000 people globally. The main symptoms in people with hEDS are joint hypermobility and pain. They may also have dislocated joints, early-onset arthritis, chronic fatigue, digestive problems, urinary incontinence, and heart valve problems. 

Classic EDS (cEDS)

This type of EDS affects the skin more than the joints. People with cEDS have stretchy, velvety, and fragile skin that bruises and tears easily. They may also have atrophic scarring, which means their scars are thin and crinkly. Other features include hyperelastic skin, fleshy growths (molluscoid pseudotumors), cigarette paper scars (thin and wrinkled scars), joint hypermobility, muscle weakness, and hernias. 

Vascular EDS (vEDS)

This is the most serious type of EDS, as it affects the blood vessels and internal organs. People with vEDS have thin and translucent skin that shows the underlying blood vessels. They may also have distinctive facial features such as a thin nose, thin upper lip, small earlobes, and prominent eyes. The main complication of vEDS is the rupture of blood vessels, intestines, or uterus, which can be life-threatening.

Other EDS Types

The other 10 types of EDS are as follows:

• Kyphoscoliotic EDS
• Arthrochalasia EDS
• Dermatosparaxis EDS
• Brittle cornea syndrome
• Cardiac-valvular EDS
• Spondylodysplastic EDS 
• Musculocontractural EDS
• Myopathic EDS
• Periodontal EDS
• Classical-like EDS

Ehlers-Danlos Syndrome Life Expectancy

The effect of EDS on life expectancy depends on the type and severity of the condition. Most types do not greatly affect life expectancy, although they may reduce the quality of life due to pain, fatigue or disability. Those with a higher risk of vascular complications and mortality may have a shorter lifespan.

Causes of Ehlers-Danlos Syndrome

EDS is caused by genetic variations that affect the structure or processing of collagen, a protein that provides strength and elasticity to the connective tissues. Collagen is composed of different types and subtypes that are encoded by different genes. Depending on which gene is affected, different types of collagen or related proteins may be defective or reduced in quantity or quality.

Most types of EDS are inherited in an autosomal dominant manner, indicating that a single copy of the mutated gene from either parent is sufficient to cause the disorder. More rare types of EDS are inherited in an autosomal recessive manner, in that copies of the mutated gene from both parents are needed to cause the disorder. In a few cases, a new mutation may occur during early development without any family history that can cause sudden EDS onset or worsening of symptoms.

Ehlers-Danlos Syndrome Diagnosis

The diagnosis of EDS is based on a combination of physical examination, medical and family history, as well as genetic testing.

The symptoms will usually indicate a connective tissue disorder and will be investigated individually to pinpoint the precise cause. During a physical exam, a specialist is likely to measure blood pressure and heart rate, check for joint hypermobility, as well as assess skin elasticity, fragility, scarring, bruising, and transparency.

Joint hypermobility can be evaluated using the Beighton score or Beighton scale. This measures how far certain joints can bend or stretch. A score of 5 or more out of 9 indicates joint hypermobility.

Other tests may include:

• Echocardiogram (ECG) to check for heart valve problems.
• Skin Biopsy to check for changes in collagen production or structure.

Genetic Testing is the most definitive investigation for Ehlers-Danlos syndrome that confirms an EDS diagnosis by identifying the specific gene mutation involved. This is not yet available or conclusive for hEDS, in which case, the diagnosis is based on clinical criteria and the exclusion of other possible causes.

Genes Tested in Diagnosing EDS
Type of EDS	Mutated Gene(s)	Affected Proteins
Hypermobile EDS	Unknown	-
Classical EDS	COL5A1, COL5A2, COL1A1	Type V and I Collagen
Vascular EDS	COL3A1, COL1A1 12.3-15.3 (women)	Type III and I Collagen 11.6-14.6 (women)
Classical-like EDS	TNXB	Tenascin XB(women)
Cardiac-valvular EDS	COL1A2	Type I Collagen
Kyphoscoliotic EDS	PLOD1, FKBP14	LH1, FKBP22
Arthrochalasia EDS	COL1A1, COL1A2	Type I Collagen
Dermatosparaxis EDS	ADAMTS2	ADAMTS-2
Brittle cornea syndrome	ZNF469, PRDM5	ZNF469, PRDM5
Spondylodysplastic EDS	B4GALT7, B3GALT6, SLC39A13	B4GalT7, B3GalT6, ZIP13
Musculocontractural EDS	CHST14, DSE	D4ST1, DSE
Myopathic EDS	COL12A1	Type XII Collagen
Periodontal EDS	C1R, C1S	C1r, C1s

Who Treats Ehlers-Danlos Syndrome?

Symptoms will likely first appear in a medical checkup carried out by a GP, who may refer the patient to a rheumatologist, dermatologist or other specialist, depending on the main presenting complaint. It is most common for a rheumatologist specializing in the joints to suspect EDS, who will subsequently refer the patient to a genetic testing facility.

After the diagnosis of EDS is confirmed, who treats EDS will depend upon the symptoms and their severity.^[3]

Treatment of Ehlers-Danlos Syndrome

There is no curative treatment for EDS. Current EDS therapies aim to manage the symptoms and usually require help from a team of specialists or appropriate healthcare providers.^[4]

Medications and therapies prescribed to help those with EDS are discussed below.

Medication

Medication can help to relieve the main symptoms and often consists of:

• Pain relievers, such as acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs), which may help ease joint or muscle pain.
• Antihypotensive agents, such as midodrine, that may help keep blood pressure slightly lower to prevent strain and damage to blood vessels.

Other medications may be prescribed to treat specific problems, such as digestive issues, urinary incontinence, or dysautonomia (a disorder of the autonomic nervous system that affects heart rate, blood pressure, temperature regulation, and other functions).

These need to be carefully considered by an experienced medical professional to avoid potentially severe complications.

Ehlers-Danlos Syndrome Supportive Therapy

Supportive therapies available to EDS patients include:

• Physical therapy: Exercises are often recommended to help strengthen the muscles around the joints to prevent dislocation and improve stability. Physiotherapists can also advise on how to avoid injuries and protect the joints from excessive stress.
• Occupational Therapy: An occupational therapist can help to provide solutions for those unable to perform or manage daily activities. They also offer those with EDS advice on assistive devices, such as braces, splints, or orthotics, that can support the joints, reduce stress, and minimize injury.
• Psychotherapy or Cognitive Behavioural Therapy (CBT): These can provide psychological support and help one to cope with long-term symptoms such as pain, anxiety or depression.
• Genetic Counselling: It may be useful for some with EDS to find out more about the genetic cause of their condition and how it may impact family planning.
• Alternative Therapies: Acupuncture, massage, or biofeedback may be of use for lowering pain and anxiety. Consult with a doctor before starting any new medication or therapy.

Regular Checkups

Some patients with EDS may require routine cardiovascular screening or regular appointments to monitor their vitals. Alternatively, their doctor may show them how to regularly check their blood pressure and heart rate at home. Any drastic symptoms or changes will require urgent medical attention, such as sudden severe pain, swelling, bleeding, or shock. This can help to quickly treat severe or life-threatening complications, such as organ or blood vessel rupture.

Surgery

Surgery may be needed to repair severely damaged or dislocated joints, hernias, or organ prolapse or to treat life-threatening complications, such as aortic dissection or intestinal rupture. However, due to the high risk of bleeding, infection, and poor wound healing in people with EDS, surgery should only be performed by surgeons experienced in treating those with the condition.^[5]

Tips for Managing and Living with EDS

EDS can affect many aspects of life, such as physical health, mental health, social relationships, education, work, and daily activities. With proper treatment and support, people with EDS can lead fulfilling and productive lives.

Below are some useful tips for managing EDS:

1. Skin and wound care are essential for people with EDS. To prevent skin damage and infection, those with EDS should try to avoid injuries, such as cuts, burns, or sun exposure, and use gentle soaps and moisturizing products. To manage scarring, it can be helpful to use silicone gel or sheets, massage the scars, and protect them from sunlight.
2. Avoiding Overexertion: Those with EDS should avoid activities that put too much strain on the joints or skin, such as contact sports, heavy lifting, or sun exposure. They may also need to rest frequently, pace themselves and conserve their energy throughout the day.
3. Diet and Hydration: Nutritional deficiencies, blood pressure issues and digestive problems are common in those with EDS. It is advisable for them to keep hydrated and opt for a balanced diet with adequate vitamin D3, iron, and other nutrients. Foods that trigger allergies, intolerances, or inflammation ought to be avoided. Medications, caffeine, smoking and other factors that affect blood pressure or clotting are also highly discouraged.
4. Emotional and Psychological Well-being: People with EDS may face emotional and psychological challenges such as anxiety, depression, low self-esteem or reduced quality of life. Where possible or available, coping strategies such as meditation, yoga, music, art, or psychotherapy should be deployed to help.
5. Building a Support Network: A support network can provide emotional support, practical help, information, and resources. This extends to dependable family and friends, as well as EDS communities, forums, groups, or organizations that can connect people who share similar experiences and challenges.

Conclusion

EDS is a complex and challenging condition that affects connective tissues, giving rise to sometimes debilitating symptoms. Treatment is multi-modal, often relying on an accurate genetic diagnosis, a team of experienced healthcare professionals and a well-equipped healthcare provider. Those with the condition need to be aware of their vulnerabilities to overexertion, injury, infection and high blood pressure. EDS therapies, organizations and communities can provide lifelong support that helps those with the condition lead fulfilling and productive lives.

To search for the best Medical Genetics Doctors and Medical Genetics Healthcare Providers worldwide, please use the Mya Care search engine.

To search for the best doctors and healthcare providers worldwide, please use the Mya Care search engine.

Sources: