Ehlers-Danlos syndrome (EDS) is a group of hereditary connective tissue disorders characterized by defects of the major structural protein in the body (collagen). Collagen, a tough, fibrous protein, plays an essential role in “holding together,” strengthening, and providing elasticity to bodily cells and tissues. Due to defects of collagen, primary EDS symptoms and findings include abnormally flexible, loose joints (articular hypermobility) that may easily become dislocated; unusually loose, thin, “stretchy” (elastic) skin; and excessive fragility of the skin, blood vessels, and other bodily tissues and membranes.
The different types of EDS were originally categorized in a classification system that used Roman numerals (e.g., EDS I to EDS XI), based upon each form’s associated symptoms and findings (clinical evidence) and underlying cause. A revised, simplified classification system (revised nosology) has since been described in the medical literature that categorizes EDS into six major subtypes, based upon clinical evidence, underlying biochemical defects, and mode of inheritance.
Each subtype of EDS is a distinct hereditary disorder that may affect individuals within certain families (kindreds). In other words, parents with one subtype of EDS will not have children with another EDS subtype. Depending upon the specific subtype present, Ehlers-Danlos syndrome is usually transmitted as an autosomal dominant or autosomal recessive trait.
The symptoms and findings associated with Ehlers-Danlos syndrome (EDS) may vary greatly in range and severity from case to case, depending upon the specific form of the disorder present and other factors. However, the primary findings associated with EDS typically include abnormal “looseness” (laxity) and excessive extension (hyperextension) of joints; susceptibility to partial or complete joint dislocations; chronic joint pain; a tendency to develop degenerative joint disease (osteoarthritis) at an early age; unusually loose, thin, elastic skin; and excessive fragility of the skin, blood vessels, and other bodily tissues and membranes. Due to tissue fragility, affected individuals may easily bruise; experience prolonged bleeding (hemorrhaging) after trauma; have poor wound healing; develop “parchment-like,” thin scarring; and/or have other associated abnormalities.
In many individuals with EDS, associated symptoms and findings may become apparent during childhood. More rarely, depending upon the specific disorder subtype present, certain abnormalities may be apparent beginning at birth (congenital). In addition, in other individuals, such as those with mild disease manifestations, the disorder may not be recognized until adulthood.
The different forms of EDS were formally classified in the 1980s using a Roman numeral system. This categorization identified at least 10 major forms of the disorder based upon genetic and biochemical abnormalities as well as associated symptoms and findings. However, a simplified, revised, updated classification system has since been published in the medical literature that classifies EDS into six primary subtypes as well as some other forms of EDS, based upon the specific underlying biochemical cause, mode of inheritance, major and minor symptoms, and physical findings. The revised classification system serves to further differentiate between the various forms of the disorder as well as some related disorders.
The original classification system differentiates between severe and mild forms of classic EDS (EDS I and II). In the revised categorization, EDS I and II are reclassified as one subtype, known as EDS classical type. According to reports in the medical literature, in individuals with this subtype, associated skin abnormalities may vary greatly, ranging from mild, moderate, to severe in certain affected families (kindreds). EDS classical type may be characterized by excessive laxity and extension of the joints (hypermobility); susceptibility to recurrent sprains and dislocations of certain joints, such as the knees and shoulders; abnormally increased elasticity and extension (hyperextensibility) of the skin; and tissue fragility, potentially leading to degeneration or “splitting” of the skin, abnormal healing of skin wounds, and characteristic, thin, “parchment-” or “paper-like” (papyraceous) scarring that often becomes discolored and widened. Such scarring may occur primarily over certain prominent bony areas (pressure points), such as the shins, knees, elbows, and forehead. In individuals with EDS classical type, additional findings may include the formation of relatively small, fleshy, tumor-like skin growths (molluscoid pseudotumors) and/or hard, round, movable lumps (calcified spheroids) under the skin; unusually “velvety” skin; diminished muscle tone (hypotonia); and/or flat feet (pes planus). EDS classical type may also be characterized by easy bruisability, often occurring in the same areas; abnormal displacement (prolapse) of certain organs due to tissue fragility, such as protrusion of part of the stomach upward through an opening in the diaphragm (hiatal hernia); and/or an increased risk of certain complications after surgical procedures. For example, postsurgical complications may include protrusion of certain organs through weak areas in surrounding membranes, muscles, or other tissues (postsurgical hernias). In addition, some individuals with this subtype may have a deformity of one of the heart valves (mitral valve prolapse), allowing blood to leak backwards into the left upper chamber of the heart (mitral insufficiency), and/or, more rarely, abnormal widening (dilatation) of a region of the aorta, the major blood vessel of the body.
EDS hypermobility type was formerly classified as EDS III or benign hypermobility syndrome. This form of the disorder is primarily characterized by generalized, excessive extension (hypermobility) of the large and small joints. Additional findings may include abnormally increased skin elasticity, an unusually smooth or “velvet-like” consistency of the skin, and/or easy bruising. Skin abnormalities and bruising susceptibility may be extremely variable from case to case. Some individuals with EDS hypermobility type may develop chronic, potentially disabling joint pain and be prone to recurrent dislocations, particularly of the knee, shoulder, and jaw (i.e., temporomandibular) joints.
EDS vascular type (formerly EDS IV or EDS arterial-ecchymotic type) is primarily characterized by unusually thin, transparent skin with prominent underlying veins, particularly in the chest and abdominal areas; a susceptibility to severe bruising from minor trauma; and tissue fragility, potentially resulting in spontaneous rupture of certain membranes and tissues. For example, affected individuals may be prone to spontaneous rupture of certain mid-sized or large arteries or the intestine (bowel), leading to life-threatening complications. Because acute pain in the abdominal or flank area may indicate possible arterial or intestinal rupture, such symptoms require immediate, emergency medical attention. Individuals with EDS vascular type may also be prone to developing abnormal channels between certain arteries and veins (arteriovenous fistula, e.g., carotid-cavernous sinus fistula) and have an increased risk of weakening of arterial walls and associated bulging of certain arteries (aneurysms), such as those supplying the head and neck (carotid arteries) and within the skull (intracranial). Aneurysms may be prone to rupturing, potentially resulting in life-threatening complications. Females with EDS vascular type may also be at risk for arterial bleeding and rupture of the uterus during pregnancy as well as vaginal tearing, uterine rupture, and/or other complications during delivery. In addition, affected individuals may be prone to experiencing certain complications during and after surgical procedures, such as separation of the layers of a surgical wound (dehiscence).
Individuals with EDS vascular type may also have abnormally decreased levels of fatty tissue under skin layers (subcutaneous adipose tissue) of the hands, arms, legs, feet, and face. As a result, some affected individuals may have a characteristic facial appearance, including thin lips; a thin, pinched nose; relatively large, prominent eyes; hollow cheeks; and tight, lobeless ears. In addition, skin of the hands and feet may appear prematurely aged (acrogeria). Additional symptoms and findings associated with this EDS subtype may include a deformity in which the foot is twisted out of position at birth (clubfoot); hypermobility that may be limited to joints of the fingers and toes (digits); the early onset of varicose veins, which are unusually widened, twisted veins visible under the skin; and spontaneous rupture of muscles and tendons. In addition, some with this EDS subtype may be susceptible to abnormal accumulations of air and blood in the chest cavity (pneumohemothorax) and/or associated collapse of the lungs (pneumothorax).
In individuals with EDS kyphoscoliosis type (formerly EDS VI), certain symptoms and findings may be apparent at birth (congenital). These include abnormal sideways curvature of the spine (congenital scoliosis) that becomes progressively severe; diminished muscle tone (hypotonia); and generalized, excessive extension and looseness (laxity) of the joints. In children with the disorder, severe hypotonia may cause delays in the acquisition of certain motor skills, and affected adults may lose the ability to walk by the second or third decade of life. Additional findings associated with EDS kyphoscoliosis type may include easy bruising, tissue fragility and associated degenerative (atrophic) scarring of the skin, a risk of spontaneous arterial rupture, abnormally reduced bone mass (osteopenia), and unusually small corneas (microcornea). In addition, because the opaque, inelastic membrane covering the eyeballs (sclera) may be unusually fragile, minor trauma may result in rupture of the sclera, rupture of the transparent region in the front of the eyes (cornea), and/or detachment of the nerve-rich membrane in the back of the eyes (retina).
EDS arthrochalasia type (formerly EDS VII, Autosomal Dominant [EDS VIIA and VIIB]) is primarily characterized by dislocation of the hips at birth (congenital hip dislocation); severe, generalized, excessive extension of the joints (hypermobility); and recurrent partial dislocations of affected joints (subluxations), such as