Vascular Ehlers-Danlos Syndrome (vEDS)

Vascular Ehlers-Danlos syndrome (vEDS) is a heritable connective tissue disorder that makes the connective tissue very fragile, particularly in the blood vessels and hollow organs. vEDS can cause life-threatening complications, such as aneurysm, dissection, and rupture of the arteries and rupture of organs, mainly the bowel.

vEDS is a rare condition that affects roughly 1 in 100,000 – 200,000 people.

Key signs and symptoms of vEDS include:

• Easy, unusual, and/or unexplained bruising, especially bruises unrelated to injury or in unusual places such as the cheeks or back
• Arterial aneurysm, dissection, and rupture, particularly before age 40
• Carotid-cavernous sinus fistula formation without trauma
• Bowel perforation, most commonly in the sigmoid colon
• Spontaneous pneumothorax
• Uterine rupture during the third trimester of pregnancy
• Characteristic facial features, including prominent eyes, narrow nose, thin lips, and attached or absent earlobes

You can learn more about the features of vEDS by selecting different body parts from the menu.

Genetic Basis

vEDS is caused by genetic variants in the COL3A1 gene. The COL3A1 gene provides instructions for making type III collagen, a major protein in the walls of blood vessels and hollow organs. vEDS can be caused by faulty type III collagen or by a reduced amount of type III collagen.

Humans have two copies of the COL3A1 gene. People with vEDS typically have a pathogenic variant in one copy of the COL3A1 gene. There are also specific genetic variants in the COL1A1 gene that can cause vEDS, but these are very rare.

Inheritance

vEDS is inherited in an autosomal dominant pattern. This means it can be passed on and inherited equally by males and females. People with vEDS have a 50% chance of passing the condition on to each child they have.

About half of people with vEDS inherit it from one of their parents, while the other half are the first person in their family to have vEDS because the genetic variant started in them. When a genetic variant starts in a person for the first time, it is known as a new or “de novo” variant.

Genetic testing is used to see if a person has a genetic variant that causes vEDS. Genetic testing should be considered if a person has any of the major criteria or several minor criteria, particularly in people under the age of 40.

Major Criteria

1. Family history of vEDS with a documented causative variant in COL3A1
2. Arterial rupture at a young age
3. Spontaneous sigmoid colon perforation in the absence of known diverticular disease or other bowel pathology
4. Uterine rupture during the third trimester in the absence of previous C-section and/or severe peripartum perineum tears
5. Carotid-cavernous sinus fistula (CCSF) formation in the absence of trauma

Minor Criteria

1. Bruising unrelated to identified trauma and/or in unusual sites such as the cheeks and back
2. Thin, translucent skin with increased venous visibility
3. Characteristic facial appearance
4. Spontaneous pneumothorax
5. Acrogeria
6. Talipes equinovarus
7. Congenital hip dislocation
8. Hypermobility of small joints
9. Tendon and muscle rupture
10. Keratoconus
11. Gingival recession and gingival fragility
12. Early-onset varicose veins (under age 30 and starting before pregnancy if female)

vEDS can cause a variety of symptoms in many different areas of the body, so people with vEDS may require providers in multiple different specialties to manage their care.

Key aspects of care include:

Early diagnosis
Early diagnosis allows people with vEDS to receive appropriate medical care and lifestyle advice, which is shown to improve outcomes in vEDS.

Genetic testing
It is important to confirm the diagnosis of vEDS through genetic testing. This helps to rule out other conditions that can cause similar symptoms but may be managed differently.

Genetic counseling
vEDS is inherited in an autosomal dominant pattern, so people with vEDS have a 50% chance of passing the condition on to each child they have. People with vEDS and their partners may benefit from discussing what this means for them with a genetic counselor. Pregnancy also carries additional risks for people with vEDS, so it is important to discuss pregnancy risks and management when family planning.

Pregnancy management
Pregnancy is known to carry significant risks for people with vEDS. Pregnancy should be managed carefully and with consideration of the diagnosis.

Lifestyle advice
People with vEDS should have discussions with their doctors about activities that may increase the risks of arterial or hollow organ rupture. People with vEDS should avoid:

• • Contact and collision sports
  • Heavy lifting and pushing
  • Muscle straining
  • Sudden or large increases in blood pressure
  • Repetitive or excessive joint movement

People with vEDS are encouraged to do regular, low-intensity exercise for their health and well-being.

Medical management
All medical professionals involved in a person’s care should be aware of their vEDS diagnosis and the risks associated with it. vEDS can affect all areas of medical care, so it is important to consider tissue fragility and the potential for sudden, severe, and life-threatening complications during any interventions. Conservative approaches should be considered when possible, and elective procedures should be avoided due to the higher surgical risks associated with vEDS.

Emergency care
Emergency providers must be made aware that a person has vEDS in order to provide appropriate care. People with vEDS are encouraged to carry emergency information with them to help them get the right emergency care. People with vEDS require tailored medical care, and conservative management options should be considered before surgery due to the higher surgical risks associated with vEDS.

Medications
High blood pressure puts stress on the blood vessel walls, which are very fragile in people with vEDS. Medications are often used to keep blood pressure at a normal or low level and to prevent large changes in blood pressure. Beta-blockers and angiotensin II receptor blockers (ARBs) have been shown to improve clinical outcomes for those with vEDS when combined with specialist care and advice.

Vascular imaging
Most people with vEDS should have regular vascular imaging to screen for potential complications, which may allow them to be addressed in a planned procedure rather than in an emergency. It is important to investigate suspected vascular events because symptoms can be subtle.

Support
Mental health support can be beneficial for anyone with a lifelong medical condition. There are many ways to get mental health support, including through doctors, therapists, charity organizations, and support groups. The Ehlers-Danlos Society offers a monthly virtual support group for people with vEDS and parents of people with vEDS.

Diagnosis, natural history, and management in vascular Ehlers-Danlos syndrome (Byers et al., 2017)
https://doi.org/10.1002/ajmg.c.31553

The 2017 International Classification of the Ehlers-Danlos Syndromes (Malfait et al., 2017)
https://doi.org/10.1002/ajmg.c.31552

A multi-institutional experience in vascular Ehlers-Danlos syndrome diagnosis (Shalhub et al., 2020)
https://doi.org/10.1016/j.jvs.2019.04.487

Diagnosis and management of vascular Ehlers-Danlos syndrome: Experience of the UK national diagnostic service (Bowen et al., 2023)
https://doi.org/10.1038/s41431-023-01343-7

Surveillance and monitoring in vascular Ehlers-Danlos syndrome in European Reference Network for Rare Vascular Diseases (VASCERN) (Van de Laar et al., 2022)
https://doi.org/10.1016/j.ejmg.2022.104557

Vascular Ehlers-Danlos Syndrome: Long-Term Observational Study (Frank et al., 2019)
https://doi.org/10.1016/j.jacc.2019.01.058

Molecular diagnosis in vascular Ehlers-Danlos syndrome predicts pattern of arterial involvement and outcomes (Shalhub et al., 2014)
https://doi.org/10.1016/j.jvs.2014.01.070

A multi-institutional experience in the aortic and arterial pathology in individuals with genetically confirmed vascular Ehlers-Danlos syndrome (Shalhub et al., 2019)
https://doi.org/10.1016/j.jvs.2019.01.069\

Assessment of arterial damage in vascular Ehlers-Danlos syndrome: A retrospective multicentric cohort (Adham et al., 2022)
https://doi.org/10.3389/fcvm.2022.953894

Arterial complications of vascular Ehlers-Danlos syndrome (Eagleton, 2016)
https://doi.org/10.1016/j.jvs.2016.06.120

Spontaneous pneumothorax and hemothorax frequently precede the arterial and intestinal complications of vascular Ehlers-Danlos syndrome (Shalhub et al., 2019)
https://doi.org/10.1002/ajmg.a.61094

Bowel perforation in vascular Ehlers-Danlos syndrome. A systematic review (El Masri et al, 2019)
https://doi.org/10.1111/1346-8138.12057

Management of colonic complications of vascular Ehlers-Danlos syndrome: a systematic review and evidence-based management strategy (Speake et al., 2020)
https://doi.org/10.1111/codi.14749

Natural history ofgastrointestinal manifestations in vascular Ehlers–Danlos syndrome: A 17-year retrospective review (Frank et al., 2018)
https://doi.org/10.1111/jgh.14522

Spontaneous Colon Perforations Associated with a Vascular Type of Ehlers-Danlos Syndrome (Yoneda et al., 2014)
https://doi.org/10.1159%2F000363373

The type of variants at the COL3A1 gene associates with the phenotype and severity of vascular Ehlers-Danlos syndrome (Frank et al., 2015)
https://doi.org/10.1038/ejhg.2015.32

Vascular Ehlers-Danlos Syndrome: A Comprehensive Natural History Study in a Dutch National Cohort of 142 Patients (Demirdas et al., 2024) 
https://doi.org/10.1161/CIRCGEN.122.003978 

Cardiovascular Management of Aortopathy in Children: A Scientific Statement From the American Heart Association (Morris et al., 2024) 
https://doi.org/10.1161/CIR.0000000000001265 

Zevra Therapeutics is developing ACER-002 (celiprolol) tablets for the treatment of vEDS in people with a COL3A1 variant to reduce the risk of arterial and other hollow organ clinical events.

For more information on the ongoing trial, please click here.

Information on how to participate can be found here.

The VEDS Movement

Annabelle’s Challenge

FIGHT vEDS

DEFY Foundation