Ehlers–Danlos syndromes

Ehlers–Danlos syndromes (EDS) are a group of genetic connective tissue disorders.[1] Symptoms may include loose joints, stretchy skin, and abnormal scar formation.[1] These can be noticed at birth or in early childhood.[2] Complications may include aortic dissection, joint dislocations, scoliosis, chronic pain, or early osteoarthritis.[1][3]

EDSs are due to a mutation in one of more than a dozen different genes.[1] The specific gene affected determines the specific EDS.[1] Some cases result from a new mutation occurring during early development, while others are inherited in an autosomal dominant or recessive manner.[1] This results in defects in the structure or processing of collagen.[1] Diagnosis is often based on symptoms and confirmed with genetic testing or a skin biopsy.[3] People may be misdiagnosed with hypochondriasis, depression, or chronic fatigue syndrome.[3]

No cure is known.[5] Treatment is supportive in nature.[3] Physical therapy and bracing may help strengthen muscles and support joints.[3] While some disorders result in a normal life expectancy, those that affect blood vessels generally result in a shorter life expectancy.[5]

EDSs affect about one in 5,000 people globally.[1] The prognosis depends on the specific disorder.[3] Excess mobility was first described by Hippocrates in 400 BC.[6] The syndromes are named after two physicians, Edvard Ehlers from Denmark and Henri-Alexandre Danlos from France, who described them at the turn of the 20th century.[7]

Ehlers–Danlos syndromes
PMC3504533 1471-2415-12-47-2 (cropped)
Individual with an EDS displaying skin hyperelasticity
SpecialtyMedical genetics, rheumatology
SymptomsOverly flexible joints, stretchy skin, abnormal scar formation[1]
ComplicationsAortic dissection, joint dislocations, osteoarthritis[1]
Usual onsetBirth or early childhood[2]
TypesHypermobile, classic, vascular, kyphoscoliosis, arthrochalasia, dermatosparaxis, brittle cornea syndrome, others[4]
Risk factorsFamily history[1]
Diagnostic methodGenetic testing, skin biopsy[3]
Differential diagnosisMarfan syndrome, cutis laxa syndrome, familial joint hypermobility syndrome[3]
PrognosisDepends on specific disorder[3]
Frequency1 in 5,000[1]

Signs and symptoms

Signs vary widely based on the specific EDS the person has. This group of disorders affects connective tissues, most typically in the joints, skin, and blood vessels and causes effects ranging from mildly loose joints to life-threatening complications.[8] Major signs and symptoms are listed below.


Musculoskeletal symptoms include hyperflexible joints that are unstable and prone to sprain, dislocation, subluxation, and hyperextension.[7][9] There can be an early onset of advanced osteoarthritis,[10] chronic degenerative joint disease,[10] swan-neck deformity of the fingers,[11] and Boutonniere deformity of the fingers. Tearing of tendons or muscles may occur.[12] Deformities of the spine, such as scoliosis (curvature of the spine), kyphosis (a thoracic hump), tethered spinal cord syndrome, and occipitoatlantoaxial hypermobility may also be present.[13] There can also be myalgia (muscle pain) and arthralgia (joint pain),[14] which may be severe and disabling. Trendelenburg's sign is often seen, which means that when standing on one leg, the pelvis drops on the other side.[15] Osgood–Schlatter disease, a painful lump on the knee, is common as well.[16] In infants, walking can be delayed (beyond 18 months of age), and bottom-shuffling instead of crawling occurs.[17]

Ehlers-Danlos syndrome3

Individual with EDS showing hypermobile fingers

Ehlers-Danlos thumb

Individual with an EDS displaying hypermobile thumb

Ehlers-Danlos syndrome2

Individual with EDS displaying hypermobile metacarpophalangeal joints


The weak connective tissue causes fragile skin that tears easily,[10] atrophic "cigarette paper" scars, and easy bruising.[1][7][18] Redundant skin folds, especially on the eyelids also happen.[10][19] Molluscoid pseudotumors,[20] especially on pressure points. Petechiae,[21] subcutaneous spheroids,[20] livedo reticularis, and piezogenic papules are less common.[22] In vascular EDS, thin, translucent, and extremely fragile skin that tears easily is also a symptom.


Atrophic scar in a case of EDS

PMC3567970 1752-1947-7-35-1 (cropped)

Translucent skin in vascular EDS

Ehlers-Danlos syndrome4

Individual with EDS displaying skin hyperelasticity


Other manifestations

PMC2856381 IJD-55-86-g002
Gorlin's sign in a case of EDS

Because it is often undiagnosed or misdiagnosed in childhood, some instances of EDSs have been mischaracterized as child abuse.[40]

The pain associated with the disorders may be severe.[41]


The collagen fibril and EDS: (a) Normal collagen fibrils are of uniform size and spacing. Fibrils from a patient with dermatosparaxis (b) show dramatic alterations in fibril morphology with severe effects on tensile strength of connective tissues. Patients with classical EDS (c) show composite fibrils. Fibrils from a TNX-deficient patient (d) are uniform in size and no composite fibrils are seen. TNX-null (e) fibrils are less densely packed and not as well aligned to neighboring fibrils.

Only some EDSs can be positively identified as tied to specific genetic variation.

Mutations in these genes can cause EDSs:

Mutations in these genes usually alter the structure, production, or processing of collagen or proteins that interact with collagen. Collagen provides structure and strength to connective tissue. A defect in collagen can weaken connective tissue in the skin, bones, blood vessels, and organs, resulting in the features of the disorder.[1] Inheritance patterns depend on the specific syndrome. Most forms of EDSs are inherited in an autosomal dominant pattern, which means only one of the two copies of the gene in question must be altered to cause a disorder. A few are inherited in an autosomal recessive pattern, which means both copies of the gene must be altered for a person to be affected by a disorder. It can also be an individual (de novo or "sporadic") mutation.[42]


A diagnosis can be made by an evaluation of medical history and clinical observation. The Beighton criteria are widely used to assess the degree of joint hypermobility. DNA and biochemical studies can help identify affected individuals. Diagnostic tests include collagen gene-mutation testing, collagen typing via skin biopsy, echocardiogram, and lysyl hydroxylase or oxidase activity. However, these tests are not able to confirm all cases, especially in instances of an unmapped mutation, so clinical evaluation by a geneticist remains essential. If multiple individuals in a family are affected, performing prenatal diagnosis may be possible using a DNA information technique known as a linkage study.[43] Knowledge about EDSs among practitioners is poor.[44][45] Research is ongoing to identify genetic markers for all types.[46]


As of 2017, 13 EDSs had been characterized, with a significant overlap in features.[4]

Hypermobile EDS (hEDS, formerly categorized as type 3) is characterized primarily by joint hypermobility affecting both large and small joints, which may lead to recurrent joint dislocations and subluxations (partial dislocation). In general, people with this type have soft, smooth, and velvety skin with easy bruising and chronic pain of the muscles and/or bones.[4] The mutation that causes this type of EDS is unknown. Less skin involvement is seen than other types. No genetic test for this type is available.

Classical EDS (cEDS, formerly categorized as type 1) is associated with extremely elastic (stretchy), smooth skin that is fragile and bruises easily; wide, atrophic scars (flat or depressed scars); and joint hypermobility. Molluscoid pseudotumors (calcified hematomas over pressure points such as the elbow) and spheroids (fat-containing cysts on forearms and shins) are also frequently seen. Hypotonia and delayed motor development may occur.[4] The mutation that causes this type of EDS is in the genes COL5A1, COL5A2, and COL1A1. It involves the skin more than hEDS.

Vascular EDS (vEDS, formerly categorized as type 4) is characterized by thin, translucent skin that is extremely fragile and bruises easily. Arteries and certain organs such as the intestines and uterus are also fragile and prone to rupture. People with this type typically have short stature, and thin scalp hair. It also has characteristic facial features including large eyes, an undersized chin, sunken cheeks, a thin nose and lips, and ears without lobes.[47] Joint hypermobility is present, but generally confined to the small joints (fingers, toes). Other common features include club foot, tendon and/or muscle rupture, acrogeria (premature aging of the skin of the hands and feet), early onset varicose veins, pneumothorax (collapse of a lung), recession of the gums, and a decreased amount of fat under the skin.[4] Is can be caused by the mutations in the COL3A1 gene.

Kyphoscoliosis EDS (kEDS, formerly categorized as type 6) is associated with severe hypotonia at birth, delayed motor development, progressive scoliosis (present from birth), and scleral fragility. Affected people may also have easy bruising, fragile arteries that are prone to rupture, unusually small corneas, and osteopenia (low bone density). Other common features include a "marfanoid habitus" which is characterized by long, slender fingers (arachnodactyly), unusually long limbs, and a sunken chest (pectus excavatum) or protruding chest (pectus carinatum).[4] It can be caused by mutations in the gene PLOD1.

Arthrochalasia EDS (aEDS, formerly categorized as types 7A & B) is characterized by severe joint hypermobility and congenital hip dislocation. Other common features include fragile, elastic skin with easy bruising, hypotonia, kyphoscoliosis (kyphosis and scoliosis), and mild osteopenia.[4] Type-I collagen is usually affected. It is very rare, with about 30 cases reported. It is more severe than the hypermobility type. Mutations in the genes COL1A1 and COL1A2 cause it.

Dermatosparaxis EDS (dEDS, formerly categorized as type 7C) is associated with extremely fragile skin leading to severe bruising and scarring; saggy, redundant skin, especially on the face; and hernias. It is extremely rare, with around 10 cases reported.

Brittle cornea syndrome is characterized by thin cornea, early-onset progressive keratoglobus or keratoconus, and blue sclerae.[4] Classic symptoms, such as hypermobile joints and hyperelastic skin, are also seen often.[48]

Classical-like EDS (clEDS) is characterized by skin hyperextensibility with velvety skin texture and absence of atrophic scarring, generalized joint hypermobility with or without recurrent dislocations (most often shoulder and ankle), and easily bruised skin or spontaneous ecchymoses (discolorations of the skin resulting from bleeding underneath).[4]

Spondylodysplastic EDS (spEDS) is characterized by short stature (progressive in childhood), muscle hypotonia (ranging from severe congenital, to mild later-onset), and bowing of limbs.[4]

Musculocontractural EDS (mcEDS) is characterized by congenital multiple contractures, characteristically adduction-flexion contractures and/or talipes equinovarus (clubfoot), characteristic craniofacial features, which are evident at birth or in early infancy, and skin features such as skin hyperextensibility, bruising, skin fragility with atrophic scars, and increased palmar wrinkling.[4]

Myopathic EDS (mEDS) is characterized by congenital muscle hypotonia and/or muscle atrophy that improves with age, proximal joint contractures (joints of the knee, hip and elbow), and hypermobility of distal joints (joints of the ankles, wrists, feet and hands).[4]

Periodontal EDS (pEDS) is characterized by severe and intractable periodontitis of early onset (childhood or adolescence), lack of attached gingiva, pretibial plaques, and family history of a first-degree relative who meets clinical criteria.[4]

Cardiac-valvular EDS (cvEDS) is characterized by severe progressive cardiac-valvular problems (aortic valve, mitral valve), skin problems (hyperextensibility, atrophic scars, thin skin, easy bruising), and joint hypermobility (generalized or restricted to small joints).[4]


Until 1997, the classification system for EDS included 10 specific types, and also acknowledged that other extremely rare types existed. At this time, the classification system underwent an overhaul and was reduced to six major types using descriptive titles. Genetic specialists recognize that other types of this condition exist, but have only been documented in single families. Except for hypermobility (type 3), the most common type of all ten types, some of the specific mutations involved have been identified and they can be precisely identified by genetic testing; this is valuable due to a great deal of variation in individual cases. However, negative genetic test results do not rule out the diagnosis, since not all of the mutations have been discovered; therefore, the clinical presentation is very important.[49]

Forms of EDSs in this category may present with soft, mildly stretchable skin, shortened bones, chronic diarrhea, joint hypermobility and dislocation, bladder rupture, or poor wound healing. Inheritance patterns in this group include X-linked recessive, autosomal dominant, and autosomal recessive. Examples of types of related syndromes other than those above reported in the medical literature include:

  • 305200 – type 5
  • 130080 – type 8 – unspecified gene, locus 12p13
  • 225310 – type 10 – unspecified gene, locus 2q34
  • 608763 – Beasley–Cohen type
  • 130070 – progeroid form – B4GALT7
  • 606408 – due to Tenascin-X deficiency – TNXB
  • 130090 – type unspecified
  • 601776D4ST1-deficient Ehlers–Danlos syndrome (adducted thumb-clubfoot syndrome) CHST14

Differential diagnosis

Several disorders share some characteristics with EDSs. For example, in cutis laxa, the skin is loose, hanging, and wrinkled. In an EDS, the skin can be pulled away from the body, but is elastic and returns to normal when let go. In Marfan syndrome, the joints are very mobile and similar cardiovascular complications occur. People with an EDSs tend to have a "marfanoid" appearance (e.g., tall, skinny, long arms and legs, "spidery" fingers). However, physical appearance and features in several EDSs also have characteristics including short stature, large eyes, and the appearance of a small mouth and chin, due to a small palate. The palate can have a high arch, causing dental crowding. Blood vessels can sometimes be easily seen through translucent skin, especially on the chest. The genetic connective tissue disorder, Loeys-Dietz syndrome, also has symptoms that overlap with EDSs.[50]

In the past, Menkes disease, a copper metabolism disorder, was thought to be an EDS. Patients are not uncommonly misdiagnosed with fibromyalgia, bleeding disorders, or other disorders that can mimic EDS symptoms. Because of these similar disorders and complications that can arise from an unmonitored case of an EDS, a correct diagnosis is important.[51] Pseudoxanthoma elasticum (PXE) is worth consideration in diagnosis.[52]


No cure is known for Ehlers–Danlos syndromes; treatment is supportive. Close monitoring of the cardiovascular system, physiotherapy, occupational therapy, and orthopedic instruments (e.g., wheelchairs, bracing, casting) may be helpful. This can help with stabilizing the joints and preventing injury. Orthopedic instruments are helpful for the prevention of further joint damage, especially for long distances, although individuals are advised not to become dependent on them until other mobility options have been exhausted. Patients should avoid activities that cause the joint to lock or overextend.[53]

A physician may prescribe casting to stabilize joints. Physicians may refer a patient to an orthotist for orthotic treatment (bracing). Physicians may also consult a physical and/or occupational therapist to help strengthen muscles and to teach people how to properly use and preserve their joints.[54][55]

Aquatic therapy promotes muscular development and coordination.[56] With manual therapy, the joint is gently mobilized within the range of motion and/or manipulations.[54][55] If conservative therapy is not helpful, surgical joint repair may be necessary. Medication to decrease pain or manage cardiac, digestive, or other related conditions may be prescribed. To decrease bruising and improve wound healing, some patients have responded to vitamin C.[57] Special precautions are often taken by medical care workers because of the sheer number of complications that tend to arise in EDS patients. In vascular EDSs, signs of chest or abdominal pain are considered trauma situations.[58]

Cannabis may help some with pain levels.[59]

In general, medical intervention is limited to symptomatic therapy. Before pregnancy, patients with an EDS should have genetic counseling and familiarize themselves with the risks to their own bodies that pregnancy poses. Children with an EDS should be provided with information about their disorder so they can understand why they should avoid contact sports and other physically stressful activities. Children should be taught that demonstrating the unusual positions that they can maintain due to loose joints should not be done, as this may cause early degeneration of the joints. Emotional support along with behavioral and psychological therapy can be useful. Support groups can be immensely helpful for patients dealing with major lifestyle changes and poor health. Family members, teachers, and friends should be informed about EDSs so they can accept and assist the child.[60]


The instability of joints, leading to (sub)luxations and joint pain, often require surgical intervention in people with an EDS. Instability of almost all joints can happen, but appear most often in the lower and upper extremities, with the wrist, fingers, shoulder, knee, hip, and ankle being most common.[54]

Common surgical procedures are joint debridement, tendon replacements, capsulorraphy, and arthroplasty. After surgery, the degree of stabilization, pain reduction, and patient satisfaction can improve, but surgery does not guarantee an optimal result: Patients and surgeons report being dissatisfied with the results. Consensus is that conservative treatment is more effective than surgery,[25] particularly since patients have extra risks of surgical complications due to the disease. Three basic surgical problems arise due to an EDS: the strength of the tissues is decreased, which makes the tissue less suitable for surgery; the fragility of the blood vessels can cause problems during surgery; and wound healing is often delayed or incomplete.[54] If considering surgical intervention, seeking care from a surgeon with extensive knowledge and experience in treating people with an EDS and joint hypermobility issues would be prudent.

Local anesthetics, arterial catheters, and central venous catheters cause a higher risk of bruise formation in people with an EDS. People with EDSs also show a resistance to local anaesthetics.[61] Resistance to xylocaine and bupivacaine is not uncommon, and carbocaine tends to work better in people with an EDS. Special recommendations for anesthesia in people with an EDS are prepared by orphananesthesia and deal with all aspects of anesthesia for people with an EDS.[62] Detailed recommendations for anesthesia and perioperative care of people with an EDS should be used to improve safety.[63]

Surgery in people with an EDS requires careful tissue handling and a longer immobilization afterward.


The outlook for individuals with an EDS depends on the specific EDS they have. Symptoms vary in severity, even in the same disorder, and the frequency of complications varies. Some people have negligible symptoms, while others are severely restricted in daily life. Extreme joint instability, chronic musculoskeletal pain, degenerative joint disease, frequent injuries, and spinal deformities may limit mobility. Severe spinal deformities may affect breathing. In the case of extreme joint instability, dislocations may result from simple tasks such as rolling over in bed or turning a doorknob. Secondary conditions such as autonomic dysfunction or cardiovascular problems, occurring in any type, can affect prognosis and quality of life. Severe mobility-related disability is seen more often in hypermobile EDS than in classical EDS or vascular EDS.

Although all EDSs are potentially life-threatening, most patients have a normal lifespan. However, those with blood-vessel fragility have a high risk of fatal complications, including spontaneous arterial rupture, which is the most common cause of sudden death. The median life expectancy in the population with vascular EDSs is 48 years.[64]


Ehlers–Danlos syndromes are inherited disorders estimated to occur in about one in 5,000 births worldwide. Initially, prevalence estimates ranged from one in 250,000 to 500,000 people, but these estimates were soon found to be too low, as the disorders received further study and medical professionals became more adept at diagnosis. EDSs may be far more common than the currently accepted estimate due to the wide range of severities with which the disorder presents.[65]

The prevalence of the disorders differs dramatically. The most commonly occurring is hypermobile EDS, followed by classical EDS. The others are very rare. For example, fewer than 10 infants and children with dermatosparaxis EDS have been described worldwide. Some EDSs are more common in Ashkenazi Jews. For example, the chance of being a carrier for dermatosparaxis EDS is one in 248 in Ashkenazi Jews, whereas the prevalence of this mutation in the general population is one in 2,000.[66]

Society and culture

Gary "Stretch" Turner
Gary "Stretch" Turner showing his extreme Ehlers Danlos syndrome
  • In the 19th century, several sideshow performers were billed as the Elastic Skin Man, the India Rubber Man, and Frog Boy. They included such well-known individuals (in their time) as Felix Wehrle, James Morris, and Avery Childs.[67]
  • Several current celebrities have an EDS:
    • Actress Cherylee Houston has hypermobile EDS and uses a wheelchair; she was the first full-time disabled actress on Coronation Street.[68]
    • An EDS may have contributed to the virtuoso violinist Niccolò Paganini's skill, as he was able to play wider fingerings than the normal violinist.[69]
    • Science blogger Yvette d'Entremont (the Science Babe) has an EDS.[70]
    • Adult film star Mandy Morbid has discussed the impact her EDS has on her mobility and her life.[71]
    • Rei Haycraft, lead singer for the hard rock band Raimee, artist, and illustrator, has created songs and a documentary about living with an EDS, as well as written songs about its impact on her life.[72][73]
    • American disability-rights activist Annie Segarra has an EDS, and talks about the condition on her Annie Elainey YouTube channel.[74]
    • Eric "The Actor" Lynch, frequent caller to The Howard Stern Show, had arthrochalasia EDS, resulting in his mangled fingers.[75]
    • Singer Mandy Harvey gradually lost her hearing as a result of a disorder; by the time she was 19, she was legally deaf. Ten years later, at age 29, she competed in America's Got Talent, season 12, finishing in fourth place.[76][77]
    • Contortionist Daniel Browning Smith has hypermobile EDS and holds the current Guinness World Record for the most flexible man as of 2018.
    • Gary "Stretch" Turner (shown right), a sideshow performer in the Circus Of Horrors, has an extreme form of EDS. He holds the current Guinness World Record for most elastic skin with 6 inches.

Other species

Ehlers–Danlos-like syndromes have been shown to be hereditary in Himalayan cats, some domestic shorthair cats,[78] and in certain breeds of cattle.[79] It is seen as a sporadic condition in domestic dogs.

Ehlers-Danlos syndrome 2

EDS in a dog

Ehlers-Danlos Syndrome 1

Same dog with EDS

Ehlers-Danlos syndrome 3

EDS in same dog showing an atrophic scar


St Bernard (dog) with Ehlers-Danlos-like syndrome showing hyperextensible skin

Degenerative suspensory ligament desmitis (DSLD) is a similar condition seen in many breeds of horses. It was originally notated in the Peruvian Paso and thought to be a condition of overwork and older age. However, DSLD is being recognized in all age groups and all activity levels. It has even been noted in newborn foals. The latest research has led to the renaming of the disease as equine systemic proteoglycan accumulation, after the possible systemic and hereditary components being delineated by the University of Georgia.[80][81]


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External links

External resources
Aortic aneurysm

An aortic aneurysm is an enlargement (dilation) of the aorta to greater than 1.5 times normal size. They usually cause no symptoms except when ruptured. Occasionally, there may be abdominal, back, or leg pain.They are most commonly located in the abdominal aorta, but can also be located in the thoracic aorta. Aortic aneurysms cause weakness in the wall of the aorta and increase the risk of aortic rupture. When rupture occurs, massive internal bleeding results and, unless treated immediately, shock and death can occur.

Screening with ultrasound is indicated in those at high risk, prevention is by decreasing risk factors such as smoking, and treatment is either by open or endovascular surgery. Aortic aneurysms resulted in about 152,000 deaths worldwide in 2013, up from 100,000 in 1990.


Carbohydrate sulfotransferase 14 is an enzyme that in humans is encoded by the CHST14 gene.

Collagen, type V, alpha 1

Collagen alpha-1(V) chain is a protein that in humans is encoded by the COL5A1 gene.This gene encodes an alpha chain for one of the low abundance fibrillar collagens. Fibrillar collagen molecules are trimers that can be composed of one or more types of alpha chains. Type V collagen is found in tissues containing type I collagen and appears to regulate the assembly of heterotypic fibers composed of both type I and type V collagen. This gene product is closely related to type XI collagen and it is possible that the collagen chains of types V and XI constitute a single collagen type with tissue-specific chain combinations. Mutations in this gene are associated with Ehlers-Danlos syndrome, types I and II.

Degenerative disease

Degenerative disease is the result of a continuous process based on degenerative cell changes, affecting tissues or organs, which will increasingly deteriorate over time.In neurodegenerative diseases cells of the central nervous system stop working or die via neurodegeneration. An example of this is Alzheimer's disease. The other two common groups of degenerative diseases are those that affect circulatory system (e.g. coronary artery disease) and neoplastic diseases (e.g. cancers).Many degenerative diseases exist and some are related to aging. Normal bodily wear or lifestyle choices (such as exercise or eating habits) may worsen degenerative diseases, but this depends on the disease. Sometimes the main or partial cause behind such diseases is genetic. Thus some are clearly hereditary like Huntington's disease. Sometimes the cause is viruses, poisons or other chemicals. The cause may also be unknown.Some degenerative diseases can be cured, but not always. It might still be possible to alleviate the symptoms.

Ehlers-Danlos Society

The Ehlers-Danlos Society is an international non-profit organization dedicated to patient support, scientific research, advocacy, and increasing awareness for the Ehlers-Danlos syndromes (EDS), hypermobility spectrum disorder (HSD), and related medical disorders. The society has organized multiple events around the world in an attempt to raise awareness for EDS. These events include a rally in Baltimore’s Inner Harbor, and a conference in India. The society also organizes symposiums dedicated to research on EDS. The 2016 symposium resulted in the reclassification of Ehlers-Danlos subtypes.

Hypermobility syndrome

Hypermobility syndrome (HMS), Hypermobility Spectrum Disorder (HSD), or joint hypermobility syndrome (JHS) is a heritable connective tissue disorder that affects the joints and ligaments in a person's body. It comes in different degrees of severity, the least being similar to double-jointedness, but if it is progressively more serious it can create more problems for someone. These can include the inability to walk properly or for long distances, and pain in affected areas. In some cases, people with HMS are subjected to hypersensitive nerves and a weaker immune system. It also can have an effect on exhaustion levels and some cases cause depressive episodes.

It is a genetic disorder. It is similar to other connective tissue disorders such as Ehlers–Danlos syndrome.

Intractable pain

Intractable pain, also known as Intractable Pain Disease or IP, is a severe, constant pain that is not curable by any known means and which causes a bed or house-bound state and early death if not adequately treated, usually with opioids and/or interventional procedures. It is not relieved by ordinary medical, surgical, nursing, or pharmaceutical measures. Unlike the more common chronic pain, it causes adverse biologic effects on the body's cardiovascular, hormone, and neurologic systems. Patients experience changes in testosterone, estrogen, cortisol, thyroid hormones, and/or pituitary hormones. Both men and women require testosterone, however many doctors neglect to test women for low testosterone. Untreated Intractable Pain can cause death.[1]


Kyphoscoliosis describes an abnormal curvature of the spine in both a coronal and sagittal plane. It is a combination of kyphosis and scoliosis. This musculoskeletal disorder often leads to other issues in patients, such as under-ventilation of lungs, pulmonary hypertension, difficulty in performing day-to-day activities, psychological issues emanating from anxiety about acceptance among peers, especially in young patients. It can also be seen in syringomyelia, Friedreich's ataxia, spina bifida, Kyphoscoliotic Ehlers-Danlos Syndrome (kEDS), and Duchenne muscular dystrophy due to asymmetric weakening of the paraspinal muscles.

Lara Bloom

Lara Bloom (born March 25, 1980) is the International Director of the Ehlers-Danlos Society. Lara is a patient expert and advocate for rare diseases, specializing in the Ehlers-Danlos syndromes. In 2012 she carried the torch at the London Paralympic Games.

Mitral insufficiency

Mitral regurgitation (MR), Mitral insufficiency (abbreviation MI best avoided because it is more commonly used in lieu of myocardial infarction), or mitral incompetence is a disorder of the heart in which the mitral valve does not close properly when the heart pumps out blood. It is the abnormal leaking of blood backwards from the left ventricle, through the mitral valve, into the left atrium, when the left ventricle contracts, i.e. there is regurgitation of blood back into the left atrium. MR is the most common form of valvular heart disease.

Painful fat herniation

Painful fat herniation, described as painful feet due to fat herniations through the thin fascial layers of the weight-bearing parts of the heel is rare, piezogenic pedal papules or Piezogenic papules are very common. These papules can also be found in wrist areas and commonly found in connective tissue disorders, especially Ehlers Danlos Syndrome. However, due to their preponderence amongst humans, their presence does not automatically mean the existence of Ehlers-Danlos syndrome and in most cases they are of little significance.


A scar is an area of fibrous tissue that replaces normal skin after an injury. Scars result from the biological process of wound repair in the skin, as well as in other organs and tissues of the body. Thus, scarring is a natural part of the healing process. With the exception of very minor lesions, every wound (e.g., after accident, disease, or surgery) results in some degree of scarring. An exception to this are animals with complete regeneration, which regrow tissue without scar formation.

Scar tissue is composed of the same protein (collagen) as the tissue that it replaces, but the fiber composition of the protein is different; instead of a random basketweave formation of the collagen fibers found in normal tissue, in fibrosis the collagen cross-links and forms a pronounced alignment in a single direction. This collagen scar tissue alignment is usually of inferior functional quality to the normal collagen randomised alignment. For example, scars in the skin are less resistant to ultraviolet radiation, and sweat glands and hair follicles do not grow back within scar tissues. A myocardial infarction, commonly known as a heart attack, causes scar formation in the heart muscle, which leads to loss of muscular power and possibly heart failure. However, there are some tissues (e.g. bone) that can heal without any structural or functional deterioration.

Small fiber peripheral neuropathy

Small fiber peripheral neuropathy is a type of peripheral neuropathy that occurs from damage to the small unmyelinated peripheral nerve fibers. These fibers, categorized as C fibers and small Aδ fibers, are present in skin, peripheral nerves, and organs. The role of these nerves is to innervate the skin (somatic fibers) and help control autonomic function (autonomic fibers). It is estimated that 15-20 million people in the United States have some form of peripheral neuropathy.

Vertebral artery dissection

Vertebral artery dissection (VAD) is a flap-like tear of the inner lining of the vertebral artery, which is located in the neck and supplies blood to the brain. After the tear, blood enters the arterial wall and forms a blood clot, thickening the artery wall and often impeding blood flow. The symptoms of vertebral artery dissection include head and neck pain and intermittent or permanent stroke symptoms such as difficulty speaking, impaired coordination and visual loss. It is usually diagnosed with a contrast-enhanced CT or MRI scan.Vertebral dissection may occur after physical trauma to the neck, such as a blunt injury (e.g. traffic collision), strangulation or manipulation, but may also happen spontaneously. 1–4% of spontaneous cases have a clear underlying connective tissue disorder affecting the blood vessels. Treatment is usually with either antiplatelet drugs such as aspirin or with anticoagulants such as heparin or warfarin.Vertebral artery dissection is less common than carotid artery dissection (dissection of the large arteries in the front of the neck). The two conditions together account for 10–25% of non-hemorrhagic strokes in young and middle-aged people. Over 75% recover completely or with minimal impact on functioning, with the remainder having more severe disability and a very small proportion (about 2%) dying from complications. It was first described in the 1970s by the Canadian neurologist C. Miller Fisher.

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