Ehlers-Danlos Syndrome

Ehlers-Danlos Syndrome was named after physicians Edvard Ehlers, from Denmark, and Henri Alexandre-Danlos, from France, and it is a rare genetic disorder of the connective tissue. If not diagnosed and treated, it can be life-threatening.

1 in 2,500 to 1 in 5,000 people have Ehler-Danlos Syndrome (EDS). The disorder is either inherited (passed on from parent to child), or can occur spontaneously. If the disorder is inherited, the child will invariably have the same type of EDS as the parent.

The disorder happens because of mutations in the genes that code collagen proteins – which are the main structural component of the connective tissue -, as well as the genes that code enzymes which help build collagen. The end result is the alteration of the structure, production, or processing of collagen.

Collagen is produced in cells called fibroblasts, and its role is to give and preserve structure, as well as to confer strength and flexibility to the connective tissue. There are over twenty types of collagen, which are produced by different genes, have somewhat different properties. and are present in different locations.

Collagen is prevalent in fibrous connective tissues (fascia, tendons, ligaments, dermis), it reinforces the cartilage, and it constitutes about 90 percent of the bone’s organic compounds (which is almost one third of the bone’s entire makeup). Collagen is also abundant in corneas, blood vessels, viscera, intervertebral discs and the dentin in teeth.

Different types of gene mutation, and their combination, result in different kinds of EDS disorders. While many collagen gene mutations have been discovered and can be identified by genetic testing, there are some mutations that are yet unknown. Therefore, a negative genetic test does not rule out the diagnosis. Complete physical examination, as well family medical history are required in order to establish if a person has EDS or not.

There are six main types of Ehlers-Danlos Syndrome: classical, vascular, hypermobility, kyphoscoliosis, arthrochalasear, and dermatosparaxis – the last three with less than 60, 30, and 10 reported cases, respectively. One type of EDS can have some of the features of another, and all types of EDS share the same symptoms: joined hypermobility (increased range of movement of joints), stretchy skin, fragile tissue, as well as postural orthostatic tachycardia syndrome, and gastrointestinal disorders. There are other forms of EDS, but they are either extremely rare, with only very few cases reported, or they are not well characterized.

Types of Ehlers-Danlos Syndrome, signs and symptoms

Classical type (types 1 and 2):
Altered proteins:
Collagen type I is predominant in skin (dermis), tendons, ligaments, and fascia. It is also found in arterial walls, cornea, the endomysium surrounding muscle fibers, fibrocartilage, and the organic part of bones and teeth. It also helps repairing wounds by forming scars.

Collagen type V is a minor component of predominately type I collagen fibrils that are found in connective tissue. It is essential for the formation of type I collagen fibrils, as well as other types of collagen fibrils. It is found in interstitial tissue, and it is associated with the placenta.

Signs and Symptoms:
– severe (for type 1) to mild and moderate (for type 2) skin involvement: very stretchy skin, atrophic scars (a sunken recess in the skin, which has a pitted appearance), calcified hematomas associated with the scars, tendency to bruise easily.
– joint issues: joint hypermobility, joint instability, dislocations, subluxations

Hypermobility type (type 3):
Altered proteins:
Collagen type III forms reticular fibers, which provide a very delicate network supporting individual cells and certain organs (lynph nodes, spleen, liver). Collagen type III is found in artery walls, skin, intestines, uterus, tendons, and bones. It also plays a role in wound healing.

Tenascin X (TNXB) is glycoprotein in skin, joints, and muscles. Deficiency in TNXB causes reduced collagen density and fragmented elastic fibers.

Signs and Symptoms:
– severe joint issues: Joint hypermobility, joint instability, dislocations, and subluxations
– chronic musculoskeletal pain
– hypotonia and frequent muscles cramps
– moderate to severe impairment in daily activities caused by chronic and severe pain
– degenerative arthritis
– neuropathic pain
– hearing impairing and/or sensitivity
– early osteoarthritis
– skin involvement is present, but less severe

Vascular type (type 4):
Altered proteins:
Collagen type III

Signs and Symptoms:
– common features:
– characteristic facial appearances: large eyes, small chin, sunken cheeks, thin nose and lips, lobeless ears
– small stature with a slim build
– thin, pale, translucent skin, and veins that can usually be seen on the chest and abdomen

– arterial, intestinal, and uterine fragility and tearing
– spontaneous arterial rupture is the most common cause of sudden death
– arterial or intestinal rupture come with acute defuse of localized abdominal or flank pain
– complications in pregnancy due to intra-partum uterine rupture and pre- and postpartum arterial bleeding
– tendon and muscles rupture
– decrease in subcutaneous tissue, especially in the face and extremities
– easy bruising
– premature aging of the skin of the hands and feet
– early onset varicose veins
– arteriovenous fistula (is an opening between and artery and vein), and carotid-cavernous fistula
– pneumothorax (collapse of a lung), and pneumohemothorax (collapse of a lung with a collection of air or gas and blood)
– gingival recession

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