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 19 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.

Classical EDS

Classical EDS is thought to affect about 1 in 20,000 people, but those with milder forms of the disease may go undiagnosed.

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.

Classical-like EDS

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.

Cardiac-valvular EDS

Cardiac-valvular EDS is caused by mutations in the COL1A2 gene, another gene that encodes a portion of the type 1 collagen protein.

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.

Hypermobile EDS

Hypermobile EDS is thought to affect about 1 in 5,000 people, though the exact frequency of the disease is unknown.

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.

Vascular 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.

Kyphoscoliotic EDS

Kyphoscoliotic EDS is thought to affect 1 in 100,000 people.

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.

Mutations in the PLOD1 or FKBP14 genes can cause kyphoscoliotic EDS.

Arthrochalasia EDS

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.

Dermatosparaxis EDS

Dermatosparaxis EDS is caused by mutations in the ADAMTS2 gene, which encodes for a protein that is involved in collagen assembly; essentially, it allows collagen molecules to form strong fibrils.

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)

Brittle cornea syndrome is caused by mutations in the ZNF469 or PRDM5 genes that encode for proteins involved in regulating the expression of collagen proteins.

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.

Spondylodysplastic EDS

Spondylodysplastic EDS may be caused by mutations in the B4GALT7, B3GALT6, or SLC39A13 genes.

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.

Musculocontractural EDS

Musculocontractural EDS is caused by mutations in the CHST14 gene.

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

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

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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Ehlers-Danlos News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

Emily holds a Ph.D. in Biochemistry from the University of Iowa and is currently a postdoctoral scholar at the University of Wisconsin-Madison. She graduated with a Masters in Chemistry from the Georgia Institute of Technology and holds a Bachelors in Biology and Chemistry from the University of Central Arkansas. Emily is passionate about science communication, and, in her free time, writes and illustrates children’s stories.
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Özge has a MSc. in Molecular Genetics from the University of Leicester and a PhD in Developmental Biology from Queen Mary University of London. She worked as a Post-doctoral Research Associate at the University of Leicester for six years in the field of Behavioural Neurology before moving into science communication. She worked as the Research Communication Officer at a London based charity for almost two years.
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Emily holds a Ph.D. in Biochemistry from the University of Iowa and is currently a postdoctoral scholar at the University of Wisconsin-Madison. She graduated with a Masters in Chemistry from the Georgia Institute of Technology and holds a Bachelors in Biology and Chemistry from the University of Central Arkansas. Emily is passionate about science communication, and, in her free time, writes and illustrates children’s stories.
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