Classical Ehlers-Danlos syndrome

More than 90% of people affected by classical EDS have an identifiable mutation in the COL5A1 gene or the COL5A2 gene that is known to cause the condition. These genes provide instructions for making different components of type V collagen. Collagen is a protein that provides structure and strength to connective tissues throughout the body. Mutations in COL5A1 or COL5A2 lead to defects in the structure and function of type V collagen molecules. This causes the many signs and symptoms associated with classical EDS.

In rare cases, mutations in the genes encoding type I collagen ( COL1A1 gene) can be found in people with classical EDS.

A diagnosis of classical EDS is typically based on the presence of characteristic signs and symptoms. More than 90% of classical EDS patients have mutations in one of the genes encoding type V collagen (the COL5A1 gene or the COL5A2 _gene). Rare cases are caused by a mutation in the COL1A1_ gene. Genetic testing for a mutation in these genes can then be ordered to confirm the diagnosis in some cases.

Collagen typing performed on a skin biopsy may be recommended if genetic testing is not available or inconclusive. Transmission electron microscopy (TEM) (a very powerful microscopy) findings of collagen flowers on skin biopsy can support the clinical diagnosis, but cannot confirm it. Collagen is a tough, fiber-like protein that makes up about a third of body protein. It is part of the structure of tendons, bones, and connective tissues. Although this test is generally not helpful in confirming a diagnosis of classical EDS, it can be used to rule out some of the other forms of EDS.

Absence of these findings does not rule-out the diagnosis of classical EDS; however, alternative diagnoses should be considered in the absence of a type V collagen gene mutation or electron microscopy findings.

Classical EDS is inherited in an autosomal dominant manner. This means that to have the syndrome, a person needs a mutation in only one copy of the known disease-causing genes in each cell. In some cases, a person with classical EDS inherits the mutation from a parent with the syndrome. Other cases may result from new ( de novo) mutations in the gene. These cases occur in people with no history of the disorder in their family. A person with classical EDS has a 50% chance with each pregnancy of passing along the mutated gene to his or her child.

While proanthocyanidins appear to strengthen connective tissue and stabilize collagen, there is no literature to support the use of these compounds in people with Ehlers-Danlos syndrome.

The treatment of classical EDS varies based on the signs and symptoms present in each person. For example, children with hypotonia and/or delayed motor milestones may benefit from physical therapy and occupational therapy. These treatments can also help improve joint stability. Assistive devices such as braces may also be necessary depending on the severity of joint instability. Anti-inflammatory medications may be prescribed for joint pain. Because classical EDS is associated with fragile skin with abnormal wound healing, people with the syndrome, especially children, may need to wear protective bandages or pads over exposed areas, such as the knees, shins, and forehead. Children and adolescents may be monitored for the development of aortic root dilatation (enlargement of the blood vessel that distributes blood from the heart to the rest of the body).

Please speak to your healthcare provider if you have any questions about your personal medical management plan.