Ehler’s Danlos Syndrome

Ehlers-Danlos syndrome is a collection of conditions that impair the connective tissues and ligaments that support the skin, blood vessels, bones, and a variety of other tissues and organs. Connective tissue malformations cause these disorders’ signs and symptoms, which vary from minimally lax joints to deadly conditions. Numerous classification systems have been used to categorize the various types of Ehlers-Danlos syndrome. Initially, 11 subtypes of Ehlers-Danlos disorder were designated using Roman numbers (type I, type III …). In 1998, researchers suggested a more simplified categorization that cut the number of categories to six and assigned descriptive names to each class depending on their main characteristics. In 2017, researchers revised the categorization to include newly identified infrequent kinds of Ehlers-Danlos disorder. The classification done in 2017 describes 13 varieties of Ehlers-Danlos syndrome (Jacobs et al., 2018).

Jacobs et al. (2018) state that, in the overall population, the prevalence of Ehlers-Danlos syndrome, which includes all variants, is around 1 in 2000 and 1 in 6000. Since genetic origin was not a cornerstone for classification in the 1998 nosology, little epidemiological evidence is based on the latest 2017 classification scheme. One in 10,000 to one in 20,000 people are thought to be affected by the classical form of EDS. Only roughly 60 cases have been diagnosed with the EDS kyphoscoliotic variant, and only a single family has been diagnosed with the EDS dysfibronectinemic variant, making the remaining subtypes extremely rare. Some moderate cases of EDS may go unrecognized since they don’t have enough symptoms to warrant a visit to the doctor, so the overall incidence is vastly underestimated. If this is the case, mild signs and symptoms may make a diagnosis difficult; hence genetic screening is not recommended. Men are mostly infected at an average age of 5–10years, while women are diagnosed at an average age of 15–20 years. It is common to acquire Ehlers-Danlos condition through the autosomal dominant, x-linked, or autosomal recessive modes of inheritance. The average lifespan of a child with EDS depends on the form of the disorder (Jacobs et al., 2018). Ehlers-Danlos syndromes are hereditary illnesses induced by abnormalities in numerous genes such as TNXB, PLOD1, COL5A2, etc.

In EDS, organ and vascular ruptures are the most frightening and fatal consequences. Vascular and kyphoscoliotic syndromes are the most prevalent, but they have also been documented in the more popular options. The hypermobile variety of Ehlers-Danlos disorder has an extensive range of hypermobility. The lack of muscle strength in hypermobile infants might hinder the progress of motor abilities, including sitting, walking, and standing. They are susceptible to fracture and chronic discomfort. Infants with arthrochalasia suffer joint problems and both hips dislocated at birth. These diseases cause delicate, velvet skin, which is elastic and brittle. Those with the illness tend to get bruised easily, and some varieties induce aberrant scarring.

Ehlers-Danlos syndrome is a collection of genetic connective tissue illnesses that typically affect the skin, blood vessel walls, and joints. Connective tissue is a unique protein mixture and other elements that give your body’s fundamental structures strength and suppleness. Our muscles, bones, and joints are all held together by ligaments and tendons. EDS can cause loose joints and thin, easily damaged skin. Additionally, it can impair the function of organs and blood vessels. To a more significant, all forms of EDS could be traced back genetically to changes in genes encoding connective tissue chains or biogenesis-related proteins. The biomechanical repercussions of changed collagen fiber in producing tissues and the variation in impacted collagen types in the muscles distinguish EDS variations clinically. According to the previous classification, most patients with traditional EDS, i.e., types I and II, have two heterozygous genetic changes in the genitival encoding of the prevalent collagen type V sequence (COL5A1 and COL5A2).

However, vascular EDS is caused by a mutation in the gene for collagen type III found in vascular vessels, which accounts for more than 94% of cases. Four kinds of EDS, i.e., cardiac-valvular, arthrochalasia, osteogenesis imperfecta, and vascular rapture, result from dominant or recessive gene encoding alterations in collagen type I (Jacobs et al., 2018). Collagen I biogenesis-related enzymes/proteins are the sources of a few EDS-afflicting phenotypes. Dermatosparaxis is caused by ADAMTS2 mutations, which produce an N-proteinase implicated in the deletion of N-propeptides necessary for collagen I development. Kyphoscoliotic EDS is caused by a PLOD1 lysyl hydroxylase one deficiency, which affects the hydroxylation of collagen I and II lysine residues. Immunostaining on tissue samples from EDS individuals with tenascin X-deficient EDS owing to TNXB gene mutations reveals moderately decreased collagen VI expressions. Studies indicate that Tenascin X’s absence reduces gene levels of COL6A1, COL6A2, and COL6A3. Two muscle illnesses, Bethlem myalgia, and Ullrich fetal muscular dystrophy, are caused by mutations in these genes and share specific characteristics, such as atrophic scarring and EDSs.

EDS subtypes such as musculocontractural and progeroid are caused by alterations in genes encoding for proteins that are crucial to the production of proteoglycans and constituents of the CT extracellular components and display close ties to collagen fibers. Recessive variations in FKBP14 might play a role in developing kyphoscoliotic EDS. There is a possibility that this chaperone gene might affect the way the outer layer is assembled by acting as an FK506-binding peptidyl-prolyl cis-trans type of enzyme. Unlike other EDS variations, EDS-HT does not have a recognized genetic abnormality. A small number of papers have attempted to shed light on the mystery in the past. According to certain molecular studies, researchers have foTNXB mutant, or monozygotic twin mutations have been found in less than 6% of EDS-HT individuals.

Pain and exhaustion are nearly common in Ehlers-Danlos disorders. Clinical signs of an EDS are mainly joint and tissue linked, including Excessively flexible joints. Since the collagen that keeps joints together is loose, the joints may move well beyond the usual flexion and extension. Joint discomfort and misalignments are prevalent. Poor muscle tone may impair the growth of motor abilities, including walking, sitting, and standing, in young children with joint problems. Painful dislocations and long-term dislocations may result from lax joints. Babies with EDS arthrochalasia are born with hypermobility and misalignments in both hips. Skin that can be stretched. The skin will be able to stretch far more easily if you have poor connective tissue. Patients may be capable of pulling a small amount of skin from their flesh, but once it is let go, it snaps back into place. Some people report that their skin feels smooth and velvety. Those with the illness are more susceptible to bruising, and certain varieties of it may also produce irregular scarring. Wounds break open with minimal blood in the traditional type of Ehlers-Danlos disease, leaving scars that enlarge over time to create distinctive “cigarette paper” marks. In the dermatosparaxis variant, there may also be additional (redundant) flaps of skin on the face and body.

A physician suspects Ehlers-Danlos disorder when a set of symptoms and signs that have been previously characterized are found to be present in the patient. After this suspicion, a patient’s early symptoms should be evaluated to establish whether they are genuinely congruent with EDS. After a diagnosis of EDS, the first step should be to determine the degree of the disease’s effects on the health. In the case of traditional EDS, Malfait, etc., a physician suggests a method that begins with a skin examination and ends with the Beighton test. In newborns and kids, motor learning should undergo examination. Practitioners also recommend baseline echocardiography for kids under ten years. Whether simple bruising is a problem, practitioners should assess coagulation factors to identify if another concurrent bleeding disease is present. After physical manipulation, the ability of readily loose skin to instantly restore to its previous form or shape helps to assess and distinguish skin hyperextensibility from other syndromes like cutis laxa. Using MRI, echocardiography, and CT, typical cardiovascular problems, including aortic enlargement and mitral valve prolapse, may be evaluated if EDS is detected. Although certain specialist laboratory tests may be significant, EDS is normally not diagnosed by bloodwork. Unless there is an underlying problem, persons with easy bleeding and bruising will have regular coagulation testing and bleeding rates. A geneticist is subsequently recommended to be referred to for a particular subtype-level prognosis. Skin histopathology with electron microscopy can be carried out to look for traditional malformations in collagen presentation.

In EDS, arterial and tissue bursts are some of the most dreaded and fatal consequences, respectively. However, they are seen in less frequent variants and the more common cardiovascular and kyphoscoliotic varieties. The abdomen and thorax are the most common places for avascular rupture. An internal fracture is most likely to occur inside the uterus during pregnancy and the liver, spleen, and transverse colon, among other places. Regurgitation may or not accompany mitral valve collapse. Although more severe versions are less prevalent, regurgitation may vary in severity from moderate to severe (Leganger et al., 2022). Cardiomyopathy and pulmonary embolism are the usual signs and symptoms of mitral regurgitation; however, it may not become clinically relevant until a physiologic strain like during pregnancy (Bennet et al., 2021). Because of the anomalies in the fibrous tissue, patients are more susceptible to cervical failure, and labor might develop early or suddenly. There is an increased chance of major vaginal and periurethral gashes, which may lead to both disease and mortality (Pezaro et al., 2018). Osteoarthritis may be caused by recurrent joint injuries, particularly in hypermobility and traditional varieties, which may need many orthopedic surgeries.

Since EDS is not curable, a comprehensive approach to individual treatment and care should be used to avoid the disease from progressing and its associated consequences. Patients with pathology-related concerns are often cared for by specialists who focus on a narrow area of expertise. For instance, a cardiologist can evaluate and manage cardiovascular issues; similarly, an orthopedist would assess and handle musculoskeletal problems. A geneticist or a general practitioner often makes referrals to these experts. The collagen anomalies in the skin’s surface predispose them to poor tissue regeneration and necrosis. Because of this, wound healing should be careful, such as thorough closures, and stitches should stay in the restored tissue for a long time. Regular cardiovascular examination is essential for reducing the impact of the risks to the greatest extent feasible. Since hypertension burdens an otherwise vulnerable vascular system, it should be treated aggressively. Regular cardiovascular examination is essential for reducing the impact of the risks to the greatest extent feasible. Since hypertension burdens an otherwise vulnerable vascular system, it should be treated aggressively. Echocardiography is used to screen for pathological changes in the heart, including mitral valve anomalies, which may need surgical treatment to avert collapse or heart failure.

The prognosis can vary greatly depending on the variant and whether disease or death rates are more important. Patients’ environments and subtypes significantly impact morbidity and mortality (Leganger et al., 2022). Weightlifting, for example, is a risky activity for people having Ehlers-Danlos disorder hypermobile type. Still, if they are educated about it earlier and abstain from it, their life expectancy may be extended significantly. On the other hand, substantial morbidity could be predicted if the same person is repeatedly subjected to physical trauma, resulting in recurring joint destruction that may require surgical treatment (Simmonds et al., 2019). Generally, the lifespan of individuals with hypermobility and typical variants is not impacted by the condition. The longevity of individuals with arterial and kyphoscoliotic variants is considerably decreased. An individual with the vascular kind is prone to face a major cardiovascular incident by 40 years with an average longevity of 47. Additionally, individuals with the kyphoscoliotic variety have vascular shocks or even obstructive lung problems, which are recognized to diminish their life span.

This projective has been very informative since I have gained vast knowledge of the Ehler’s-Danlos Syndrome. I have known that hereditary gene mutations cause EDS and affect the connective tissues. I have learned that connective tissues are made of chemicals and proteins that offer strength and elasticity to the body. Since EDS is not curable, I have learned that a comprehensive approach to individual treatment and care should be used to prevent the disease from progressing and its associated consequences.

I have known that people with Ehlers-Danlos disorder often have abnormally flexible joints and elastic, delicate skin. This may be an issue if one has a cut that needs sutures since the skin is typically not tough enough to keep them in place. The research also informed me that vascular EDS, a more severe version of the illness, may burst the walls of one’s blood vessels, intestines, or uterus. In light of the dangers of pregnancy in women with Ehlers-Danlos disease, one should seek genetic counseling before having a family.

References

Bennett, S. E., Walsh, N., Moss, T., & Palmer, S. (2021). Understanding the psychosocial impact of joint hypermobility syndrome and Ehlers–Danlos syndrome hypermobility type: a qualitative interview study. Disability and Rehabilitation, 43(6), 795-804.

Jacobs, J. W. G., Cornelissens, L. J. M., & Veenhuizen, M. C. (Eds.). (2018). Ehlers-Danlos syndrome: a multidisciplinary approach. IOS Press.

Leganger, J., Fonnes, S., Kulas Søborg, M. L., Rosenberg, J., & Burcharth, J. (2022). The most common comorbidities in patients with Ehlers-Danlos syndrome: a 15-year nationwide population-based cohort study. Disability and Rehabilitation, 44(2), 189-193.

Pezaro, S., Pearce, G., & Reinhold, E. (2018). Hypermobile Ehlers-Danlos syndrome during pregnancy, birth, and beyond. British Journal of Midwifery, 26(4), 217-223.

Simmonds, J. V., Herbland, A., Hakim, A., Ninis, N., Lever, W., Aziz, Q., & Cairns, M. (2019). Exercise beliefs and behaviors of individuals with Joint Hypermobility Syndrome/Ehlers–Danlos syndrome–hypermobility type. Disability and Rehabilitation, 41(4), 445-455.