Genetic testing for rare types of EDS

Please note: The following text cannot and should not replace advice from the patient's healthcare professional(s). Any person who experiences symptoms or feels that something may be wrong should seek individual, professional help for evaluation and/or treatment. This information is for guidance only and is not intended to provide individual medical advice.

Ehlers-Danlos syndromes (EDS) are a collection of inherited conditions that fit into a larger group known as heritable disorders of connective tissue. Connective tissues provide support in skin, tendons, ligaments and bones.  There are different types of EDS, but some have features in common. These can include joint hypermobility (increased mobility of joints), stretchy skin and tissue fragility. The fragile skin and unstable joints found in some types of EDS are the result of faulty collagen.

Hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorders

Hypermobile EDS and hypermobility spectrum disorders are not considered rare types of EDS and are both diagnosed clinically.  Currently there is no genetic testing available for these conditions.  However, a genetic component is suspected, given the way these conditions can run in families.

Rare types of Ehlers-Danlos syndrome

There are thirteen rare types of EDS where the genetic cause has been identified and genetic testing is possible. Many of the genes that have been identified are associated with the collagen pathway. Collagen is a protein in connective tissue which acts as a ‘glue’ in the body, adding strength and elasticity. When a collagen gene is altered it causes a lack or deficiency of collagen or related proteins.  This makes the connective tissue less effective, leading to symptoms of a rare type of EDS. The different EDS rare types are Classical, Vascular, Arthrochalasia, Dermatosparaxis, Cardiac valvular, Kyphoscoliotic, Classical-like type 1, Classical-like type 2, Myopathic, Musculocontractural, Spondylodysplastic, Periodontal EDS and Brittle Cornea Syndrome.

Genetic testing for rare types of Ehlers-Danlos syndrome

If a rare type of EDS is suspected based on personal or family history this can be discussed in the first instance with a GP who can decide whether to refer to a relevant specialist (depending on the symptom) for further assessment. It is very important to have information on the family or any reliable genetic test results available.  If a specialist suspects a rare type of EDS based on medical history, family history and/or physical examination then they may offer a genetic test to confirm the diagnosis. If genetic testing takes place in a local genetics service or EDS specialist service (see below), the clinical team will discuss the process including the implications of having a genetic test and what a positive result might mean for the individual, other family members if applicable, and implications for health management.

In order to carry out the genetic testing, DNA is extracted from a sample of blood or saliva. The testing involves analysing genes that have been found to be associated with rare forms of EDS and over-lapping conditions to look for disease- causing genetic alterations in the DNA (pathogenic variants). If a person receives a diagnosis through genetic testing, then suitable family members can be offered genetic testing for the gene alteration(s) in their family.  This may involve diagnostic testing (if the family member already has symptoms) or predictive testing (to find out if they may develop symptoms).

A person who has been diagnosed with a rare type of EDS and is planning to have a child can explore options should they wish to have a child without the condition. One option is testing during pregnancy which involves tests such as amniocentesis or Chorionic villus sampling  They may also be eligible for pre-implantation genetic testing for monogenic disorders (PGT-M) that tests embryos, during in vitro fertilisation, and selects only embryos that are free of the condition for the pregnancy.

More information

The National EDS service is an NHS highly specialised service for adults and children who have or are suspected to have a rare type of EDS. A team of consultants and genetic counsellors work with both adults and children being evaluated for a rare type of EDS and support those eligible through the genetic testing process. If a rare type of EDS is confirmed, supportive resources are offered to help people manage their condition, including referrals to other specialists where recommended, liaising with other health care professionals over care and long term follow-up where needed.

The service covers England and Scotland. For information about the service and for referral eligibility please click on the following links:

EDS National Diagnostic Service (based in London) covering the South of England

EDS National Diagnostic Service (based in Sheffield) covering the North of England