Ehlers-Danlos syndrome (EDS) is a group of inherited disorders that profoundly affect connective tissues, primarily the skin, joints, and blood vessel walls. Connective tissues play a crucial role in providing structural strength and elasticity to various bodily components, primarily through proteins like elastin and collagen. However, people living with EDS have less stable collagen, often resulting in compromised connective tissue integrity. This condition can have far-reaching implications, affecting nearly every organ system, and often leading to significant co-morbidities and even reduced mortality.
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The underlying cause of EDS is a defect in one or more of the gene(s) responsible for the production of the impacted collagen protein(s). Over 19 distinct genes are known to be associated with EDS, with the specific gene affected determining the particular EDS subtype. These genetic variations often manifest in different ways, including those arising from spontaneous mutations during early development or those being passed down through inheritance in autosomal dominant or recessive patterns.
Navigating the Spectrum: Types and Traits of Ehlers-Danlos Syndrome
EDS is classified into several types, each with its own unique set of symptoms and characteristics. There are currently 13 types of EDS, most of which are rare. Here is an overview of the various types of EDS currently identified:
Type of EDS | Overview | Characteristics | Genetic Basis |
Hypermobile EDS (hEDS) | The most prevalently diagnosed type, typically represents 80 to 90% of EDS cases, with symptoms often emerging during childhood or adolescence. | Soft, smooth, fragile skin; joint hypermobility; frequent joint dislocations; scoliosis; fibromyalgia/chronic pain and osteoarthritis. | The genetic mutation has not yet been identified. |
Classical EDS (cEDS) | Thought to affect as many as 1 in 20,000 people, clinical presentation tends to be similar to that of the hEDS type. | Skin hyperextensibility, atrophic or indented scars, and joint hypermobility. | Caused by mutations in either the COL5A1 or COL5A2 gene or in rare cases, the COL1A1 gene. |
Classical-like EDS (clEDS) | Thought to affect as many as 1 in 20,000 people, clEDS is difficult to distinguish from cEDS in medical literature. | Symptoms of clEDS are very similar to those of cEDS. | Caused by mutations in the TNXB gene. |
Vascular EDS (vEDS) | The true prevalence of vEDS is unknown, but is known to be the most life-threatening type of EDS. | Causes the blood vessels and organs to be fragile and prone to tearing. Complications include aneurysm, dissection, and rupture of the arteries and rupture of organs. | Caused by mutations in the COL3A1 gene. |
Kyphoscoliotic EDS (kEDS) | Thought to impact 1 in 100,000 people. Prevalence is primarily documented in regions of Greece, Turkey, and the Middle East. | Causes kyphoscoliosis, muscle hypotonia, and joint hypermobility. | Caused by mutations in the PLOD1 gene, and in rarer cases, the FKBP14 gene. |
Arthrochalasia EDS (aEDS) | The true prevalence of aEDS is unknown. Patients are born with dislocated hips. | Symptoms include severe joint hypermobility, congenital hip dislocation, fragile, hyperextensible skin, hypotonia, and kyphoscoliosis (kyphosis and scoliosis). | Caused by mutations in the COL1A1 or COL1A2 gene. |
Dermatosparaxis EDS (dEDS) | An extremely rare condition, with only a few cases having been reported in the literature. Estimated to affect less than one of every million people. | Causes extreme skin fragility, excess loose skin and severe bruising. | Caused by mutations in the ADAMTS2 gene |
Brittle Cornea Syndrome (BCS) | This type of EDS, which usually begins in infancy or before birth, is estimated to affect less than one in a million people. | Affects the connective tissue in the eyes, ears, joints, and skin. Symptoms typically involve detached retinas and the thinning of the protective outer layer of the eye (cornea), which may lead to tearing or rupture after minor damage to the cornea. | Caused by mutations in the ZNF469 or PRDM5. |
Spondylodysplastic EDS (spEDS) | The true prevalence of spEDS is unknown. | Primarily affects the skeletal system, skin, and hair. The key signs and symptoms of spEDS include unusually flexible joints, loose and elastic skin, easy scarring, short stature, bowing of the legs, weak muscle tone, sparse scalp hair and eyebrows, and soft, doughy skin. | Caused by mutations in the B4GALT7, B3GALT6, or SLC39A13 genes. |
Musculocontractural EDS (mcEDS) | The prevalence of mcEDS is not well-established | The major characteristics include distinctive craniofacial dysmorphism, congenital contractures of thumbs and fingers, clubfeet, severe kyphoscoliosis, muscular hypotonia, hyperextensible thin skin with easy bruising and atrophic scarring, wrinkled palms, joint hypermobility, and ocular involvement. | Caused by mutations in the CHST14 or DSE gene. |
Myopathic EDS (mEDS) | The prevalence of mEDS is unknown. | The hallmark symptoms of mEDS are muscle weakness in early childhood associated with large contractures of the knee, hip, and elbow joints, also called proximal joints. Additional features include soft, doughy skin, atrophic scarring, delayed motor development, and myopathic findings in muscle biopsy. | Caused by mutations in the COL12A1 gene |
Periodontal EDS (pEDS) | True prevalence of pEDS is unknown. | Characterized by childhood or adolescence onset of severe, intractable periodontitis, lack of attached gingiva, and presence of pretibial plaques. | Caused by mutations in the C1R or C1S genes |
Cardiac-Valvular EDS (cvEDS) | Affects less than 1 in 1 million people. | Affects the heart valves and blood vessels. The main symptom is progressive weakening of heart valves, which can lead to high blood pressure or arterial disease. Other symptoms include thin and stretchy skin that bruises and scars easily, increased joint mobility and dislocation, flat feet, back pain, and early arthritis. | Caused by a mutation in the COL1A2 gene. |
It's important to note that EDS can vary significantly in terms of symptoms and severity even within the same subtype. Additionally, due to ongoing research and advancements in the field of genetics, the classification of EDS may evolve over time.
Exploring EDS Prevalence
The prevalence of EDS varies by type; however, the collective prevalence of all EDS types is estimated to be at least 1 in 5,000 individuals globally. The hypermobile and classical forms are the most common. The hypermobile type may impact 1 in 5,000 to 20,000 people, while the classical type likely occurs in 1 in 20,000 individuals.
The prevalence of EDS doesn't seem to be significantly influenced by race, gender, ethnicity, or geographic location. It’s important to note that these are estimates and the actual prevalence could be higher due to undiagnosed or misdiagnosed cases.
Common Symptoms and Characteristics
Ehlers-Danlos Syndrome (EDS) encompasses a range of symptoms that can vary depending on the specific type of EDS. However, some common symptoms and characteristics include:
Overly flexible joints: Many individuals with EDS have hypermobile joints, which means their joints can move beyond the average range of motion. The ability to over-extend joints often results in frequent dislocations among individuals living with EDS.
Skin Hyperextensibility: The skin is often hyperelastic and can be stretched beyond what is considered a normal range. Hyperelastic skin tends to result in easy bruising and scarring.
Non-healing damaged skin: While healthy skin heals from a cut or a scrape with imperceptible scarring, the skin of people with EDS rarely heals completely. Instead, damage lingers for a long time. Moreover, scar tissue is more common in EDS patients.
Tissue Fragility: The body’s organs and other structures are more vulnerable to damage. Tissue fragility can present as easy bruising and poor wound healing in many types of EDS. Some types of EDS can also cause severe fragility of the skin, blood vessels, abdominal organs, eyes, gums, and bones.
Sacroiliac (SI) Joint Dysfunction: When hEDS causes SI joint dysfunction, the main symptom is low back pain. Other common symptoms include radiating pain through the hips, groin, buttocks, and back of the thighs. In addition, a common sign of SI joint dysfunction associated with EDS is called an upslip.Â
Easy Bruising and Poor Wound Healing:Â Due to the fragility of blood vessels and tissues, individuals with EDS may bruise easily, and wounds may take longer to heal.
Muscle Weakness:Â EDS, especially hEDS, is associated with muscle pain, nighttime muscle cramps involving the calves, floppy (low tone) muscles, and worsening muscle weakness, which to some extent may be the result of avoiding exercise due to overly mobile joints. Weakness in the muscles can contribute to joint instability, resulting in a debilitating cycle of dysfunction and pain.
Gastrointestinal Issues: The GI tract is made up of connective tissue, which can be affected by EDS. This can lead to both structural and functional problems such as hernias, out-of-place organs, prolapse, disordered gut motility, and constipation.
Cardiovascular Issues:
Patients with cvEDS have progressive weakening of the heart valves and may experience blood pressure issues. cvEDS affects the connective tissue that forms the heart valves.
Patients with vEDS have weakened blood vessels that may rupture or tear spontaneously or as a result of a physical impact. This type of tearing can cause severe bleeding that may require surgery.
Patients with cEDS, clEDS and hEDS, have weak blood vessels that are easily stretched or torn. In rare cases, patients with these EDS types experience fast heart rates and low blood pressure. Some studies have shown that they may also have a high risk of heart valve dysfunction.
Autonomic Dysfunction (Dysautonomia): Many people with EDS experience dysautonomia. Common signs of dysautonomia include tachycardia (fast heart rate), hypotension (low blood pressure), dizziness/lightheadedness, gastrointestinal dysmotility (problems moving food through the digestive system), disturbed bladder function, temperature and sweating dysregulation, and sleep problems.
Eye Complications: Some common ocular complications of EDS include keratoconus, retinal detachment, high myopia, macular degeneration, dry eyes, and glaucoma. Changes in the cornea often cause dry eyes and light sensitivity, as well as blurry vision for EDS patients. In rare cases, the sclera (the white part of the eye) may turn slightly blue in EDS patients.
Chronic Fatigue (feeling tired all the time): Chronic fatigue is a common symptom in people with EDS, particularly those with hEDS. Contributing factors can include sleep disorders, muscle deconditioning, headaches, and nutritional deficiencies.
Chronic Pain (Fibromyalgia): Many patients with hEDS describe chronic generalized pain. EDS patients with chronic pain may also experience central sensitization, which describes changes in the central and peripheral nervous system that increase sensitivity to stimuli.Â
It's important to note that the severity and combination of symptoms can vary widely among individuals with EDS, and not everyone with EDS will experience all of these symptoms.
EDS Diagnostic Journey
Ehlers-Danlos Syndrome (EDS) is diagnosed through a combination of a clinical examination, medical history review, and in some cases, genetic testing. Here’s a typical diagnostic journey for EDS patients:Â
Clinical Evaluation: A healthcare provider may examine the patient’s skin and joints, looking for signs of EDS such as joints with a large range of motion, and stretchy and fragile skin.
Medical History Review: The healthcare provider will discuss the patient’s medical history, including any family history of EDS.
Genetic Testing: A genetic test can be conducted to check for mutations in the genes causing some of the types of EDS. However, for the most common form, hEDS, there is currently no genetic test available.
Skin Biopsy:Â In some cases, a skin biopsy may be performed to analyze the structure, composition, and elasticity of the skin, which can provide additional diagnostic insights.
Collaboration with Specialists:Â Collaboration with various specialists, including geneticists, rheumatologists, neurologists, cardiologists, orthopedic surgeons, and other relevant healthcare professionals, is often involved in the diagnostic process.
Exclusion of Other Conditions:Â The diagnostic journey also includes the exclusion of other connective tissue disorders or medical conditions that may present with similar symptoms. Conditions mistaken for EDS may include
Osteogenesis imperfect
Loeys–Dietz syndrome
Marfan Syndrome
Skeletal dysplasia
Mucopolysaccharidoses
Cutis laxa
Pseudoxanthoma elasticum
Ullrich congenital muscular dystrophy
Bethlem myopathy
Mast Cell Activation Syndrome (MCAS)
Postural Orthostatic Tachycardia Syndrome (POTS)
Chiari Malformation
Diagnosing EDS can be a challenging and extensive journey. Most patients consult multiple doctors before receiving a diagnosis, and some are initially told their symptoms are psychosomatic. EDS is often described as an "invisible" illness because, despite appearing healthy, patients grapple with pain and fatigue that can make everyday tasks difficult.
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Tailored Approaches to Symptom Management
Treatment for Ehlers-Danlos Syndrome (EDS) primarily focuses on managing symptoms, as there currently are no cures for any of the types of EDS. Some of the approaches to managing symptoms include:
Medication: Over-the-counter pain relievers such as acetaminophen, ibuprofen, and naproxen sodium are often used for pain management. In some types of EDS, medicines to keep your blood pressure a little low would be prescribed, as a precautionary measure to prevent damage to blood vessels.
Physical Therapy: Muscle strengthening exercises are recommended to reduce overall pain and to reduce joint dislocations.Â
Orthopedic Devices:Â Braces or splints are often utilized to provide support to unstable joints.
Surgery: Surgery may be recommended to repair joints damaged by repeated dislocations, or to repair ruptured areas in blood vessels and organs. However, surgical wounds often are difficult to heal properly because the stitches are prone to tearing through the fragile tissues.
Cardiac Monitoring:Â Regular cardiac check-ups are necessary to monitor potential cardiac complications and to prevent future life-threatening events.
Skin Care:Â Special attention to skin care can help manage the fragility and vulnerability of the skin in some EDS types.
Lifestyle Modifications and Self-Care Measures: These are important parts of managing EDS. For example, choosing sports wisely, minimizing stress on the hips, knees, and ankles, limiting how much gum is chewed to not stress the jaw, wearing supportive shoes, improving sleep routines, etc.
Genetic Counseling:Â For those with a confirmed genetic diagnosis, genetic counselling can provide information about the condition's inheritance pattern and potential risks for future generations.
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It's important to note that each treatment plan is individualized based on the specific symptoms, co-morbidities and type of EDS each person is living with. Regular follow-up with healthcare providers, including specialists familiar with EDS, is essential for comprehensive care.
Conclusion
Ehlers-Danlos Syndrome (EDS) is an intricate tapestry, with each thread representing a unique journey—one of resilience, challenges, and the pursuit of solutions and understanding. As one delves into the complexities of this connective tissue disorder, it becomes evident that awareness and knowledge are the keystones in fostering support and compassion.
The diagnostic odyssey for EDS patients is often fraught with uncertainty, misinterpretations, and the quest for validation. By recognizing the diverse symptoms, advocating for streamlined diagnostic processes, and dispelling misconceptions, we contribute to a landscape where individuals with EDS receive timely and accurate diagnoses.
Managing EDS is an ongoing narrative, where collaboration among healthcare professionals, patients, and their support networks is paramount. From medications to physical therapy, surgery to lifestyle modifications, the myriad approaches underscore the necessity for personalized care plans. Embracing genetic counselling further empowers individuals to navigate the hereditary aspects of the condition, fostering informed decisions and a sense of genetic awareness.
Yet, the journey does not end with a diagnosis and a management plan—it extends to societal understanding and empathy. EDS is, in many ways, an invisible experience. Despite outward appearances, individuals with EDS grapple with persistent pain, fatigue, and a spectrum of symptoms that impact daily life. Elevating awareness dispels harmful myths, encourages empathy, and invites a collective effort toward a more inclusive and supportive society.
References:
https://www.childrenshospital.org/conditions/ehlers-danlos-syndrome
https://www.mayoclinic.org/diseases-conditions/ehlers-danlos-syndrome/symptoms-causes/syc-20362125
https://universityhealthnews.com/daily/ehlers-danlos-syndrome-types/
https://www.verywellhealth.com/ehlers-danlos-syndrome-types-189682
https://restrightmattress.com/ehlers-danlos-syndrome-statistics/
https://medlineplus.gov/genetics/condition/ehlers-danlos-syndrome/
https://sage-answer.com/who-is-most-likely-to-get-ehlers-danlos-syndrome/
https://www.diseasemaps.org/ehlers-danlos/top-questions/prevalence/
https://www.uhn.ca/Medicine/Clinics/Ehlers-Danlos_Syndrome_Clinic
https://ehlersdanlosnews.com/health-insights/eye-problems-in-eds/
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