Ehlers-Danlos syndrome (EDS) is the name given to a group of disorders that affect connective tissue and cartilage, which provide structure to joints, tissues, organs, and skin.
Under the current 2017 classification system, 13 types of EDS are identified and many are linked to mutations in at least 20 different genes. Causative mutations are known for the more common types of EDS, but for some of the rarer types, underlying genetic mutations are yet to be identified.
Most types of EDS are associated with symptoms like hypermobility of joints (“loose” joints that extend beyond a normal range, risking dislocations), and soft and fragile skin that is easily damaged. The complications specific to a given EDS type can range from mild to life-threatening.
The disease is characterized by joint hypermobility, skin elasticity, and abnormal wound healing. Some lung complications, such as spontaneous pneumothorax (collapsed lung), have also been reported in this type of EDS.
Classical EDS is caused by mutations in the COL5A1 or COL5A2 genes, and in rare cases in the COL1A1 gene, which provide the genetic instructions necessary for making portions of type 5 and type 1 collagen protein, respectively.
About half of classical EDS cases are caused by de novo mutations — that is, mutations that are not inherited from either parent.
The symptoms of classical-like EDS are very similar to those of classical EDS, but this disease is caused by mutations in the TNXB gene. The protein encoded by TNXB is involved in the organization of structural proteins in tissues and organs, and the maintenance of connective tissues. Without this protein, tissue structures are weak and more easily damaged.
Patients with classic-like EDS may experience hernias, where internal organs like the stomach or intestines protrude through the muscle wall that usually contain it.
Patients with this type of EDS have defects in heart valves in addition to joint hypermobility and fragile skin. These heart defects can result in life-threatening heart problems.
Patients with hypermobile EDS have smooth skin and hypermobile joints, though not to the extent of patients with classical EDS. They also often develop scoliosis (abnormal sideways curvature of the spine) and osteoarthritis (inflammation of the bones). Some may develop irritable bowel syndrome (IBS).
The causative genetic mutations are not known for this form of EDS.
Patients with vascular EDS may not show hypermobility to the extent of other EDS types. This type of EDS is characterized by fragile tissues, including those of the vasculature (blood vessels and arteries), that can spontaneously rupture and be life-threatening. Around 80% of individuals with vascular EDS experience a major vascular event (like an enlarged aorta — aortic aneurysm — or an aortic dissection or tear) or organ or muscle rupture by age 40.
These patients bruise easily, and may have other vein abnormalities like varicose veins early in life.
Patients with this type of EDS develop kyphoscoliosis — a type of scoliosis and kyphosis where the spine is bent sideways and backward. Some patients with kyphoscoliotic EDS are born with kyphoscoliosis. If the kyphoscoliosis is progressive (that is, worsens with time) it can interfere with breathing and require surgery. Patients with kyphoscoliotic EDS may also develop osteoporosis (weakening of the bones). About 30% also have clubfoot (where the ankle is twisted inwards at birth).
Many of these patients have eye abnormalities that make their eyes very fragile, with tears in the eye tissue more likely than is usual.
Arthrochalasia EDS is caused by mutations in the COL1A2 and COL1A1 genes.
This type of EDS is extremely rare, and its exact frequency is unknown.
Patients are born with dislocated hips (called congenital hip dislocation). Their joints are hypermobile and frequently dislocated, to the extent that they may not be able to walk. Patients usually develop kyphoscoliosis, have weak muscle tone, and have frequent bone fractures as a result of their disease.
The frequency of this type of EDS is not known.
Patients have extremely fragile and doughy skin; often have folds of sagging excess skin, especially around the face; and they bruise easily. Large hernias are also common, and joint hypermobility can range from mild to severe.
Brittle cornea syndrome (BCS)
Patients with BCS have joint hypermobility, and thinning of the cornea (the outermost layer of the eye) is a common symptom. This thinning can lead to ruptures or tears in the cornea, which can damage vision. Other less common eye problems include nearsightedness and detached retinas. Some patients may also develop hearing loss.
Patients have short stature from childhood, poor muscle tone that ranges from mild to severe, and bowing of limbs. They also experience joint hypermobility and have soft, fragile and thin skin. Hair on the scalp and eyebrows is also often sparse.
Some patients have mild intellectual disabilities, and fragile bones caused by low bone mineral density. Some can also have eye problems caused by fragile tissues, which may cause vision loss.
The condition is also called adducted thumb and clubfoot syndrome, because patients have long, spidery fingers, and are born with adducted thumbs — thumbs twisted so that they clench in the fist — and with clubfoot. Some patients are also born with a cleft palate, and abnormalities of the heart, kidneys, and intestines. Delayed development and weak muscle tone may be evident in infancy, but cognitive development is normal in childhood.
Myopathic EDS is characterized by muscle weakness from birth that usually improves with age. Patients have joint hypermobility in the ankles, feet, wrists, and hands, and an unusual shortening of the joints in the hips, knees, and elbows.
Periodontal EDS is characterized by early and severe periodontitis (a serious gum infection that can lead to tooth loss) in childhood or adolescence, as well as detached gingiva (gum tissue that recedes from the teeth) that also promotes frequent and serious gum infections.
Last updated: Oct. 11, 2019
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