Ehlers-Danlos syndromes

Ehlers-Danlos syndromes (EDS) are genetic disorders that can be caused by mutations in several different genes, including COL5A1, COL5A2, COL1A1, COL3A1, TNXB, PLOD1, COL1A2, FKBP14 _and ADAMTS2. _However, the underlying genetic cause is unknown in some families.

Mutations in these genes usually change the structure, production, and/or processing of collagen, or proteins that interact with collagen. Collagen provides structure and strength to connective tissues throughout the body. A defect in collagen can weaken connective tissues in the skin, bones, blood vessels, and organs, resulting in the signs and symptoms of EDS.

The Ehlers-Danlos Society website has a more complete list of genes associated with EDS.

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 inheritance pattern of Ehlers-Danlos syndromes (EDS) varies by subtype. The arthrochalasia EDS, classical EDS, hypermobile EDS, periodontal EDS, some cases of myopatic EDS, and vascular forms of EDS usually have an autosomal dominant pattern of inheritance. This means that to be affected, a person needs to have a change (mutation) in only one copy of the disease-causing gene in each cell. In some cases, a person with these forms of EDS inherits the mutation from an affected parent. Other cases may result from new ( de novo) mutations in the gene; these cases occur in people with no family history of EDS. Each child of a person with autosomal dominant EDS has a 50% chance of inheriting the mutation.

The dermatosparaxis EDS, kyphoscoliosis EDS, classical-like EDS, cardiac- vascular EDS, brittle cornea syndrome, spondylodysplastic EDS, musculocontractural EDS, and some cases of myopatic EDS are inherited in an autosomal recessive pattern. This means that have any of these types of EDS, a person must have a mutation in both copies of the disease-causing gene in each cell. The parents of an affected person usually each carry one mutated copy of the gene and are referred to as carriers. Carriers typically do not show signs or symptoms of the condition. When two carriers of an autosomal recessive condition have children, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be a carrier like each of the parents, and a 25% chance to not have the condition and not be a carrier.

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 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.

For more specific information on the treatment of each subtype, please click on the links below:

• Hypermobility type
• Classic type
• Vascular type
• Kyphoscoliosis type
• Arthrochalasia type
• Dermatosparaxis type

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