Classical and Classical-like EDS

Ehlers-Danlos syndrome (EDS) is the name given to a group of genetic disorders that affect the connective tissue. Classical EDS and classical-like EDS are two of the 13 types of EDS.

As their names suggest, these two types of EDS have similar symptoms and clinical manifestations, but the underlying cause of the disease is different. Classical EDS is estimated to affect one out of 20,000 to 40,000 individuals.

Causes

Classical EDS is usually caused by mutations in the COL5A1 or COL5A2 gene. In rare cases, it may be due to mutations in the COL1A1 gene. These genes provide instructions for making collagen, an important kind of structural protein.

Classical-like EDS is caused by mutations in the TNXB gene, which provides instructions to build a protein called tenascin-X, which supports the function of collagen. In some individuals, classical-like EDS is caused by large deletions of genetic material, in which case the TNXB gene and the nearby CYP21A2 gene may both be deleted. Mutations in CYP21A2 lead to congenital adrenal hyperplasia, a genetic condition that affects the adrenal glands. These glands produce hormones and are found above the kidneys.

Inheritance

For all of the genes involved in the development of classical and classical-like EDS, everyone inherits two copies (one from each biological parent). One of the main differences between the two types is in the mode of inheritance. While EDS typically is inherited, some cases are due to new mutations in people with no family history of the disease.

Classical EDS is inherited in an autosomal dominant fashion, which means that one mutated copy of a gene is sufficient to cause the disease.

By contrast, classical-like EDS is inherited in an autosomal recessive manner, meaning that both copies of the gene must be mutated for the disease to develop. Someone with only one disease-causing mutation is called a “carrier” because they will not develop classical-like EDS, but may pass the disease-causing mutation to their biological children.

The biological children of two carriers have a 25% chance of developing classical-like EDS. While carriers do not develop classical-like EDS itself, they may have some symptoms, like unusually mobile joints, that are characteristic of EDS.

Diagnosis

Diagnosis typically begins with a physical examination to look for signs and symptoms associated with EDS, such as hypermobile joints and stretchy skin. A genetic test to look for the disease-causing mutation(s) is used to confirm the diagnosis.

Symptoms

Most people with classical or classical-like EDS have hypermobile joints, meaning they can bend their joints more than normal. This may lead to frequent joint dislocations.

People with these forms of EDS have soft, velvety skin that is more elastic than normal. They bruise easily and their wounds do not heal properly, since their scar tissue is fragile and easily damaged.

Muscle weakness (hypotonia) may occur in people with classical EDS, which can cause delayed motor development during childhood.

The tissues inside the body also may be fragile, causing symptoms like hernias — where part of an internal organ or tissue bulge through muscle — or rectal prolapse. Some patients may have heart abnormalities caused by tissue weakness in the chambers or valves of the heart.

During pregnancy, the risk of an abnormally early rupture of the amniotic sac that surrounds the fetus — sometimes called “water breaking” — is increased in women with these types of EDS.

Treatments

Management of these EDS types is generally tailored to the individual, with the goal of easing the impact of symptoms on daily life. For example, anti-inflammatory medicines may be given to ease pain, or patients may use pads or bandages to help prevent skin damage.

Interventions, such as physiotherapy to improve muscle function or surgery to correct physical deformities, may be helpful for some patients.

 

Last updated: Jan. 31, 2022, by Marisa Wexler MS

 


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