Ehlers-Danlos syndrome is a group of disorders that affect connective tissues supporting the skin, bones, blood vessels, and many other organs and tissues. Defects in connective tissues cause the signs and symptoms of these conditions, which range from mildly loose joints to life-threatening complications.

The various forms of Ehlers-Danlos syndrome have been classified in several different ways. Originally, 11 forms of Ehlers-Danlos syndrome were named using Roman numerals to indicate the types (type I, type II, and so on). In 1997, researchers proposed a simpler classification (the Villefranche nomenclature) that reduced the number of types to six and gave them descriptive names based on their major features. In 2017, the classification was updated to include rare forms of Ehlers-Danlos syndrome that were identified more recently. The 2017 classification describes 13 types of Ehlers-Danlos syndrome.

An unusually large range of joint movement (hypermobility) occurs in most forms of Ehlers-Danlos syndrome, and it is a hallmark feature of the hypermobile type. Infants and children with hypermobility often have weak muscle tone (hypotonia), which can delay the development of motor skills such as sitting, standing, and walking. The loose joints are unstable and prone to dislocation and chronic pain. In the arthrochalasia type of Ehlers-Danlos syndrome, infants have hypermobility and dislocations of both hips at birth.

Many people with the Ehlers-Danlos syndromes have soft, velvety skin that is highly stretchy (elastic) and fragile. Affected individuals tend to bruise easily, and some types of the condition also cause abnormal scarring. People with the classical form of Ehlers-Danlos syndrome experience wounds that split open with little bleeding and leave scars that widen over time to create characteristic "cigarette paper" scars. The dermatosparaxis type of the disorder is characterized by loose skin that sags and wrinkles, and extra (redundant) folds of skin may be present.

Bleeding problems are common in the vascular type of Ehlers-Danlos syndrome and are caused by unpredictable tearing (rupture) of blood vessels and organs. These complications can lead to easy bruising, internal bleeding, a hole in the wall of the intestine (intestinal perforation), or stroke. During pregnancy, women with vascular Ehlers-Danlos syndrome may experience rupture of the uterus. Additional forms of Ehlers-Danlos syndrome that involve rupture of the blood vessels include the kyphoscoliotic, classical, and classical-like types.

Other types of Ehlers-Danlos syndrome have additional signs and symptoms. The cardiac-valvular type causes severe problems with the valves that control the movement of blood through the heart. People with the kyphoscoliotic type experience severe curvature of the spine that worsens over time and can interfere with breathing by restricting lung expansion. A type of Ehlers-Danlos syndrome called brittle cornea syndrome is characterized by thinness of the clear covering of the eye (the cornea) and other eye abnormalities. The spondylodysplastic type features short stature and skeletal abnormalities such as abnormally curved (bowed) limbs. Abnormalities of muscles, including hypotonia and permanently bent joints (contractures), are among the characteristic signs of the musculocontractural and myopathic forms of Ehlers-Danlos syndrome. The periodontal type causes abnormalities of the teeth and gums.

Variants (also known as mutations) in at least 20 genes have been found to cause the Ehlers-Danlos syndromes. Variants in the COL5A1 or COL5A2 gene, or rarely in the COL1A1 gene, can cause the classical type. Variants in the TNXB gene cause the classical-like type and have been reported in a very small percentage of cases of the hypermobile type (although in most people with this type, the cause is unknown). The cardiac-valvular type and some cases of the arthrochalasia type are caused by COL1A2 gene variants; variants in the COL1A1 gene have also been found in people with the arthrochalasia type. Most cases of the vascular type result from variants in the COL3A1 gene, although rarely this type is caused by certain COL1A1 gene variants. The dermatosparaxis type is caused by variants in the ADAMTS2 gene. PLOD1 or FKBP14 gene variants result in the kyphoscoliotic type. Other rare forms of Ehlers-Danlos syndrome result from variants in other genes.

Some of the genes associated with the Ehlers-Danlos syndromes, including COL1A1, COL1A2, COL3A1, COL5A1, and COL5A2, provide instructions for making pieces of several different types of collagen. These pieces assemble to form mature collagen molecules that give structure and strength to connective tissues throughout the body. Other genes, including ADAMTS2, FKBP14, PLOD1, and TNXB, provide instructions for making proteins that process, fold, or interact with collagen. Variants in any of these genes disrupt the production or processing of collagen, preventing these molecules from being assembled properly. These changes weaken connective tissues in the skin, bones, and other parts of the body, resulting in the characteristic features of the Ehlers-Danlos syndromes.

Some genes associated with recently described types of Ehlers-Danlos syndrome have functions that appear to be unrelated to collagen. For many of these genes, it is not clear how variants lead to hypermobility, elastic skin, and other features of these conditions.

The inheritance pattern of the Ehlers-Danlos syndromes varies by type. The classical, vascular, arthrochalasia, and periodontal forms of the disorder, and likely the hypermobile type, have an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means that one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the variant from one affected parent. Other cases result from new (de novo) gene variants and occur in people with no history of the disorder in their family.

The classical-like, cardiac-valvular, dermatosparaxis, kyphoscoliotic, spondylodysplastic, and musculocontractural types of Ehlers-Danlos syndrome, as well as brittle cornea syndrome, are inherited in an autosomal recessive pattern. In autosomal recessive inheritance, two copies of a gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder.

The myopathic type of Ehlers-Danlos syndrome can have either an autosomal dominant or autosomal recessive pattern of inheritance.

There are 13 types of Ehlers-Danlos syndromes (EDS), with a significant overlap in features:

• Hypermobile EDS - 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.
• Classical EDS - 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.
• Vascular EDS - 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; thin scalp hair; and characteristic facial features including large eyes, a thin nose, and lobeless ears. 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.
• Kyphoscoliosis EDS - 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).
• Arthrochalasia EDS - 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.
• Dermatosparaxis EDS - associated with extremely fragile skin leading to severe bruising and scarring; saggy, redundant skin, especially on the face; and hernias.
• Brittle Cornea Syndrome (BCS) characterized by thin cornea, early onset progressive keratoglobus; and blue sclerae.
• Classical-like EDS (clEDS) characterized by skin hyperextensibility with velvety skin texture and absence of atrophic scarring, generalized joint hypermobility (GJH) 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).
• Spondylodysplastic EDS (spEDS) characterized by short stature (progressive in childhood), muscle hypotonia (ranging from severe congenital, to mild later-onset), and bowing of limbs.
• Musculocontractural EDS (mcEDS) 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, easy bruisability, skin fragility with atrophic scars, increased palmar wrinkling.
• Myopathic EDS (mEDS) 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).
• Periodontal EDS (pEDS) 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.
• Cardiac-valvular EDS (cvEDS) 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).

Other forms of the condition may exist but are extremely rare and are not well-characterized.

A diagnosis of the Ehlers-Danlos syndromes (EDS) is typically based on the presence of characteristic signs and symptoms. Depending on the subtype suspected, some of the following tests may be ordered to support the diagnosis:

• Collagen typing, performed on a skin biopsy, may aid in the diagnosis of vascular type, arthrochalasia type, and dermatosparaxis type. People with EDS often have abnormalities of certain types of collagen.
• Genetic testing is available for many subtypes of EDS; however, it is not an option for most families with the hypermobility type.
• Imaging studies such as CT scan, MRI, ultrasound, and angiography may be useful in identifying certain features of the condition.
• Urine tests to detect deficiencies in certain enzymes that are important for collagen formation may be helpful in diagnosing the kyphoscoliosis type.

The treatment and management of Ehlers-Danlos syndrome (EDS) is focused on preventing serious complications and relieving signs and symptoms. The features of EDS vary by subtype, so management strategies differ slightly. Because several body systems may be affected, different medical specialists may need to be involved.The main aspects of management include cardiovascular (heart) work-up, physical therapy, pain management, and psychological follow-up as needed. Surgery is sometimes recommended for various reasons in people with EDS. However, depending on the type of EDS and severity, there may be an increased risk of various surgical complications such as wound healing problems, excessive bleeding, dissection, and hernias. Surgery for non-life threatening conditions particularly should be carefully considered.

The long-term outlook (prognosis) for people with Ehlers-Danlos syndromes (EDS) varies by subtype. The vascular type is typically the most severe form of EDS and is often associated with a shortened lifespan. People affected by vascular EDS have a median life expectancy of 48 years and many will have a major event by age 40. The lifespan of people with the kyphoscoliosis form is also decreased, largely due to the vascular involvement and the potential for restrictive lung disease.

Other forms of EDS are typically not as dangerous and can be associated with normal lifespans. Affected people can often live healthy if somewhat restricted lives.

The combined prevalence of all types of Ehlers-Danlos syndrome appears to be at least 1 in 5,000 individuals worldwide. The hypermobile and classical forms are most common; the hypermobile type may affect as many as 1 in 5,000 to 20,000 people, while the classical type probably occurs in 1 in 20,000 to 40,000 people. Other forms of Ehlers-Danlos syndrome are rare, often with only a few cases or affected families described in the medical literature.