Side by side – vascular EDS and hypermobile EDS compared

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.

This information was provided by the NHS Ehlers-Danlos Syndrome National Diagnostic Service which is a specialist service for people with complex/ rare forms of Ehlers-Danlos syndrome (EDS). This service does not accept referrals from GPs or private consultants and only accepts referrals from NHS consultants.

There are 13 different types of EDS, but they do have some clinical features in common. These can include joint hypermobility, stretchy skin and tissue fragility.

Vascular EDS (vEDS) is a rare type of EDS. It is inherited in an autosomal dominant way which means that if a person has vEDS there is a 50% (1 in 2) chance that the condition will passed on to a child in each pregnancy. Vascular EDS is caused by a genetic alteration in a gene called COL3A1.  The role of this gene is to make a protein named collagen type 3 which strengthens blood vessel walls, hollow organs (such as the stomach, bladder and intestines), and the skin. A genetic alteration in COL3A1 results in a decrease in production of normal collagen type 3 which makes the tissues more fragile and prone to rupture. Vascular EDS can be very variable with regard to onset and types of symptoms even within the same family. It is a rare condition with an estimated prevalence of 1 in 90,000; approximately 750 people in the UK have vEDS, and therefore many health professionals will never have encountered someone with this condition. vEDS is confirmed only through genetic testing.

Hypermobile EDS (hEDS) is diagnosed clinically and a specific genetic cause has not yet been identified, although a genetic component is suspected, given the way that hEDS often runs in families. The prevalence of hEDS was thought to be 1: 5,000 before the use of the new diagnostic criteria that were established in 2017. The current prevalence of hEDS as diagnosed using the new criteria is unknown.

What are the main symptoms and signs of vascular EDS?

Individuals with vascular EDS may have all or some of the following key symptoms:

• Tendency to bruise very easily because the blood vessels are more fragile. Often patients will have a degree of bruising at any point in time.
• Risk of organ rupture such as the large bowel, or the uterus (womb) in pregnancy.
• Fragile blood vessels, which can lead to major complications, including tears (dissections) and ruptures.

Other features include:

• Thin skin which makes small blood vessels very visible on the upper chest and legs.
• Hypermobility and pain / dislocations often in (small) joints – where joints easily move beyond the normal expected range.
• Premature aging of the skin on hands and feet.
• Facial features, including a thin nose and lips, large eyes, small earlobes and fine sparse hair.
• Club foot.
• Partial collapse of the lung called a pneumothorax.
• Early onset severe varicose veins.

What are the main symptoms and signs of hypermobile EDS?

 New international criteria for diagnosing hypermobile EDS (hEDS) were published in 2017. To be diagnosed with hEDS, one needs to meet three separate groups of criteria (1-3 below).

1. An assessment of present and historical hypermobility using a scoring system called the Beighton Score.
2. The second criterion is divided into three features. To meet this criterion, an individual must meet two of these three features (a-c).
   1. Having at least five from a list of 12 signs and symptoms that can be identified by physical examination and additional investigations. These signs and symptoms include soft/velvety/ stretchy skin, stretchmarks, hernias, prolapse of organs (when they slip down from their normal position), mitral valve prolapse (largely treatable).
   2. Having a close family member (parent, child, brother or sister) who independently meets the criteria for a diagnosis of hypermobile EDS, though they may have different and variable symptoms.
   3. Having significant pain or unstable joints recurring daily for at least 3 months.
3. Other types of EDS and related connective tissue disorders need to have been considered by a doctor and ruled out.

Currently other signs and symptoms, including postural tachycardia syndrome  (PoTS, which causes dizziness by an abnormally large increase in heart rate), mast cell activation disorder (MCAD, which is an immunological condition) and gastrointestinal problems are not included in the 12 signs and symptoms mentioned above but an individual can still have these issues and fulfil criteria for hypermobile EDS. Research has shown there is an association between joint hypermobility and the occurrence of these signs and symptoms but as yet, there is no proof that they are linked, or due to an underlying identical cause.

 What management is recommended for people with vascular EDS?

 Heart and blood vessel monitoring and regular blood pressure checks. Blood pressure lowering medication may also be recommended.

• Investigation of any unusual signs or symptoms because of the possibility of complications related to vEDS. If any surgery or invasive procedures are being considered, the surgeon must be made aware of the diagnosis and should be encouraged to seek specialist advice.
• Wearing a Medical Alert bracelet or pendant and carrying a medical information card at all times in case of emergencies.
• Physical activity that does not strain muscles or cause a sustained increase in blood pressure and heart rate such as swimming, bicycle riding, walking or light jogging; avoiding contact sports or carrying heavy objects
• Avoiding constipation is also recommended to avoid straining that may place extra pressure on the walls of the bowel that are susceptible to tearing

What management is recommended for people with hEDS?

• Regular gentle exercise, such as walking, cycling or swimming is encouraged to keep joints mobilised and to build up muscle tone around the joints to help stabilise them. Pilates can be beneficial in helping maintain core stability and to develop good posture. Contact sports increase the risk of injury and should be avoided. A physiotherapist can help develop appropriate exercises and give advice on other suitable activities.
• Maintaining a healthy weight by sensible eating and appropriate exercise helps to avoid additional stress on the joints.
• Some people may benefit from a referral to medical specialities such as pain management, rheumatology, gastroenterology, physiotherapy or occupational therapy. This will depend upon individual needs.

Table 1. Main differences and similarities between vEDS and hEDS 

	vEDS	hEDS
Genetic cause	COL3A1 changes (more rarely, specific changes in COL1A1)	Unknown
Facial features	Characteristic ‘look’ – thin nose and lips, prominent eyes, small/absent earlobes and fine hair	No known ‘characteristic look’
Hypermobility	Tends to be only in small joints e.g. toes and fingers (however generalised joint hypermobility has also been reported)	Can be in small joints or generalised
Dislocations	Not reported as commonly as in hEDS	Quite common
Cardiovascular symptoms	A dissection or rupture as well as possible aneurysms of different vessels at a relatively young age	Heart valve abnormality (mitral valve prolapse), mild aortic root dilatation (widening)
Bruising	Bruise easily, with large bruises and  swellings often occurring after only very minor trauma	May bruise easily
Skin	Thin and translucent	Stretchmarks in unusual places
Rupture of organs	Common	Do not occur
Varicose veins	Early-onset and severe	May be present
Lung collapse (pneumothorax)	May occur	Unlikely to occur
Prolapse (uterine, rectal or bladder)	May occur	Occurs frequently

Sometimes patients with hEDS will suspect that they may have a rare form of EDS such as vascular EDS. Whilst there are common features between many of the EDS types, there is less in common between hEDS and vEDS as can be seen in table 1, especially with regard to the vascular and hollow organ complications. In children, it can sometimes be more difficult to make a distinction between different types of EDS as they will not have developed all symptoms and signs. If the doctor is uncertain, they may wish to seek specialist advice.