What is Ehlers-Danlos syndrome (EDS)?
EDS is a collection of inherited conditions that fit into a larger group known as connective tissue disorders. Connective tissues provide support in skin, tendons, ligaments and bones.There are different types of EDS, but they can have features in common. These can include joint hypermobility (increased mobility of joints), stretchy skin and tissue fragility. The fragile skin and unstable joints often found in EDS are the result of faulty collagen.
Collagen is a protein in connective tissue which acts as a ‘glue’ in the body,adding strength and elasticity. There are many different kinds including collagens types I, III and V. There are also other proteins that interact with collagen. The type of EDS depends on which collagen or interacting protein is involved.
What is Tenascin X?
Tenascin X is a protein that binds together collagen. Tenascin X deficient EDS is a condition with features that can look similar to Classical EDS without the characteristic scarring. Tenascin X deficient EDS is a rare condition and testing has only recently become available in the UK. Therefore there is limited information available and many health professionals will not have seen someone with this diagnosis.
What are the main symptoms and signs of Tenascin X deficient EDS?
Individuals with Tenascin X deficient EDS have the following features:
- Hyperelastic skin
- Hypermobility joints, that may subluxate or dislocate
- Easy Bruising
- Normal Scarring.
What causes Tenascin X deficient EDS?
Tenascin X deficient EDS is caused by alterations, also known as mutations, in the TNXB gene. This gene is the instruction for making the protein Tenascin X. The deficiency of Tenascin X causes changes to the connective tissues resulting in the clinical features seen in this condition.
How is Tenascin X deficient EDS inherited?
As well as the lack of scarring, another of the main differences between Tenascin X deficient EDS and Classical EDS is the inheritance pattern. Tenascin X deficient EDS is inherited in an autosomal recessive pattern, which means that to be affected someone must have an alteration to both copies of the TNXB gene. Someone with only one alteration is known as a carrier of Tenascin X deficient EDS and some carriers may have mild signs or symptoms of hypermobility.
Our bodies are made up of millions of cells and inside almost every cell is a complete set of our genetic material. Genes are the unique instructions which make us each individual. There are many thousands of genes, each carrying a different instruction. We have two copies of each gene. One copy of each pair is inherited from our mother, in the egg, and the other from our father, in the sperm.
Autosomal recessive inheritance
Autosomal means it can affect, and be passed on by, both males and females. Recessive means that both copies of the gene pair have an alteration. Usually the individual will have inherited one altered copy of the gene from each parent. Therefore a parent of someone with Tenascin X deficient EDS, has one normal copy of the gene and one altered copy and is known as a ‘carrier’. Carriers may experience hypermobility and some associated problems, but don’t have the easy bruising that characterizes Tenascin X deficient EDS.
When two carriers of Tenascin X deficient EDS have a child together, in any pregnancy they would have a:
- 1 in 4 chance of both passing the altered gene to their child who would then have Tenascin X deficient EDS.
- 1 in 2 chance of one parent passing on their altered gene and the other parent passing on their unaltered gene. The child would be a carrier of Tenascin X deficient EDS, like their parents.
- 1 in 4 chance of both parents passing on their normal (unaltered) copy of the gene. In this case the child will be neither a carrier nor affected by Tenascin X deficient EDS.
Individuals with Tenascin X deficient EDS will pass on one copy of their altered gene to each child and, unless their partner is also a carrier or affected by Tenascin X deficient EDS, every child will have one normal copy of the gene and one altered copy. The child will therefore be a carrier who may, or may not have mild signs and symptoms of hypermobility.
What follow up is recommended for people with Tenascin X deficient EDS?
Evidence on management of Tenascin X deficient EDS is limited, on the basis of current information we would suggest:
- Individuals should have an echocardiogram (ultrasound scan) of their heart to check the heart valves. If anything unusual is found, treatment may be recommended by the heart specialist.
- If surgery is being considered, the surgeon must be aware of the diagnosis of Tenascin X deficient EDS and they may wish to seek further advice.
- A baseline pulmonary function test is suggested in adulthood.
- It is thought that individuals with Tenascin X deficient EDS may be at increased risk of diverticulitis of the colon. Abdominal pain or changes in bowel habit should be reported to the GP.
Is there anything an individual with Tenascin X deficient EDS should avoid doing?
It is always important to maintain a healthy lifestyle and for individuals with Tenascin X deficient EDS it is specifically recommended to avoid smoking.
How can family members find out if this is relevant to them?
If family members would like further information about the implications for themselves, they should talk to their GP about the possibility of being referred to their local genetics service for genetic counseling.