Types of EDS

Under the current classification system — developed in 2017 — there are 13 different types of Ehlers-Danlos syndrome (EDS), a group of disorders that affect the connective tissue and cartilage that provide structure to joints, tissues, organs, and skin.

EDS is divided into these 13 types based on the specific symptoms of each, and its underlying genetic cause.

Most of these types are characterized by symptoms of joint hypermobility — also known as “loose” joints, ones that extend beyond a normal range, risking dislocations — and soft, fragile skin that is easily damaged and scarred. Depending on the type of EDS, symptoms can range from mild to life-threatening.

Hypermobile EDS

Hypermobile EDS is the most common form of this group of disorders. Although its exact frequency is unknown, hypermobile EDS is estimated to affect as many as 1 in 5,000 people around the world. The genetic causes of hypermobile EDS are largely unknown.

The main hallmarks of this form of EDS are smooth, fragile skin and hypermobile joints. Bone problems also are common in hypermobile EDS, especially scoliosis, or the abnormal sideways curvature of the spine, and osteoarthritis — when the cartilage that usually cushions bones in the joints wears down. Symptoms tend to be milder in this form than in other types of EDS.

Classical EDS

Classical EDS is thought to affect as many as 1 in 20,000 people. This type of EDS is characterized by joint hypermobility, skin elasticity, and abnormal wound healing.

Almost all cases of classical EDS are caused by mutations in the COL5A1 or COL5A2 genes; in rare cases, mutations in the COL1A1 gene can cause classical EDS. Mutations in all three of these genes affect the production of collagen, an important structural protein.

Classical-like EDS

As its name implies, the symptoms of classical-like EDS are very similar to those of classical EDS, but the underlying cause is different. Specifically, classical-like EDS is caused by mutations in the TNXB gene, which codes for a protein that is involved in the organization of structural proteins and the maintenance of connective tissues.

Vascular EDS

Generally considered the most severe form of the disease, vascular EDS is characterized by the abnormal fragility of the blood vessels and the internal organs. It can result in serious bleeding.

This type is usually caused by mutations in the gene COL3A1, which codes for a type of collagen, or more rarely by mutations in another collagen-coding gene called COL1A1. Vascular EDS is estimated to affect up to 1 in 50,000 people.

Cardiac-valvular EDS

Cardiac-valvular EDS is characterized by problems in the heart valves, which accompany the more common EDS symptoms of stretchy skin or overly flexible joints. It is caused by mutations in a collagen-coding gene called COL1A2.

Kyphoscoliotic EDS

The inherited kyphoscoliotic EDS is a rare form of EDS. Most of its cases have been reported in Greece, Turkey, and the Middle East. Mutations in the PLOD1 or FKBP14 genes can cause kyphoscoliotic EDS.

Patients with this type of EDS develop kyphoscoliosis — a type of scoliosis and kyphosis in which the spine is bent sideways and forward, causing bowing or rounding of the back. Often kyphoscoliotic EDS patients have a hunchback or slouching posture.

Some patients with kyphoscoliotic EDS are born with kyphoscoliosis. If it’s progressive, meaning that it worsens with time, kyphoscoliosis can interfere with breathing and require surgery.

People with kyphoscoliotic EDS may have eye abnormalities that make their eyes very fragile, with tears in the eye tissue more likely than is usual. Hearing problems also have been reported in this EDS type. Most patients have low muscle tone at birth.

Arthrochalasia EDS

Patients with arthrochalasia EDS (formerly called EDS Type VII A&B) are born with dislocated hips, called congenital hip dislocation. Their joints are typically extremely hypermobile, with frequent dislocations. Subluxations — partial dislocations of the joints — are common. These individuals often develop kyphoscoliosis, have weak muscle tone, and have problems with bone health.

Skin-related symptoms are uncommon in this form of the disease.

Arthrochalasia EDS is caused by mutations in the COL1A2 and COL1A1 genes, both of which code for collagen proteins. The prevalence of this type is unknown.

Dermatosparaxis EDS

Mutations in the ADAMTS2 gene, which encodes for a protein involved in collagen assembly, cause dermatosparaxis EDS. This type of EDS is estimated to affect less than one of every million people.

Most patients have extremely fragile and doughy skin; they often have folds of sagging excess skin, especially around the face. Those with this type bruise easily and joint hypermobility can range from mild to severe. Hernias, a condition in which an organ bulges through an abnormal opening, also are common.

Brittle cornea syndrome

Brittle cornea syndrome (BCS) is caused by mutations in the ZNF469 or PRDM5 genes, which encode for proteins involved in regulating the expression of collagen proteins. This type of EDS, which usually begins in infancy or before birth, is estimated to affect less than one in a million people.

Thinning of the cornea, the outermost layer of the eye, is a characteristic symptom. It can lead to ruptures or tears in the cornea, which can damage vision. Other eye problems, like nearsightedness and detached retinas, may occur.

Some patients also may also develop hearing loss. Joint hypermobility and skeletal problems like scoliosis also are common.

Spondylodysplastic EDS

Spondylodysplastic EDS may be caused by mutations in the B4GALT7, B3GALT6, or SLC39A13 genes, which code for proteins that are important for the production of healthy connective tissue. This form of EDS is estimated to affect less than one in a million people, and occurs before birth.

Characteristic features of this form of EDS include short stature, bowing of the legs, and abnormally sparse hair on the scalp and eyebrows. Patients usually have soft, thin skin and weak muscles. Problems with the bones and/or eyes can occur. Patients also may have mild intellectual disabilities.

Nearly all spondylodysplastic EDS patients also have narrowing of the heart’s aortic valve.

Musculocontractural EDS

Patients with musculocontractural EDS have long, spidery fingers and are born with adducted thumbs — thumbs twisted so that they clench in the fist. Clubfoot, when the foot is turned inward and down, also is common. Thus, this form of EDS is often called adducted thumb and clubfoot syndrome.

Abnormalities of the heart, kidneys, and intestines also can occur and some patients are born with a cleft palate, with openings or splits in the upper lip and/or the roof of the mouth. Delayed development and weak muscle tone may be evident in infancy, but cognitive development is usually normal in childhood.

This type of EDS can be caused by mutations in the genes CHST14 or DSE, which result in the inadequate production of a sugar molecule that increases the cohesion and stability of connective tissue. Musculocontractural EDS is estimated to affect fewer than one in a million people worldwide.

Myopathic EDS

Myopathic EDS, sometimes called mEDS, is characterized by muscle weakness and/or wasting from birth, although these symptoms usually decrease with age. Other characteristic symptoms include joint hypermobility, particularly in the extremities, and joint contractures — when they tighten or shorten causing a deformity.

This form of EDS is caused by mutations in the collagen-encoding gene COL12A1.

Periodontal EDS

As its name suggests, periodontal EDS is characterized by gum disease. An early and severe gum infection called periodontitis that manifests around puberty can lead to a loss of teeth in adulthood for these patients. Individuals with this EDS type typically have a short stature, and abnormalities like micrognathia, or an abnormally small lower jaw.

Periodontal EDS is caused by mutations in the C1R or C1S  genes, which code for immunological blood proteins. This is the rarest form of EDS.

 

Last updated: Jan. 5, 2022, by Marisa Wexler MS

 


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