Vascular Ehlers-Danlos Syndrome (vEDS)

Monogenic (Mendelian): vascular EDS, COL3A1 (rarely COL1A1); ~50% de novo^[1]

Inheritance: Autosomal dominant. Each child of an affected person has a 50% chance of inheriting the variant; risk to parents and siblings depends on whether the variant was inherited or arose de novo (low-level parental mosaicism is possible), so it is set by parental testing and the pedigree.^[1]

Familial vs de novo: Approximately 50% of vEDS cases are familial (inherited from an affected parent); approximately 50% arise as de novo COL3A1 mutations, no prior family history. This high de novo rate means a negative family history does NOT exclude vEDS.^[1]

Gene: COL3A1, encodes type III procollagen; structural defect → arterial, uterine, and intestinal fragility

Variant type: most variants disrupt assembly of type III collagen fibrils; null (haploinsufficient) variants carry a better prognosis^[3]

Vascular EDS (vEDS): 1 in 50,000 to 1 in 200,000^[1]

Most life-threatening EDS subtype

Diagnosis is molecular: vascular EDS is confirmed by a pathogenic COL3A1 variant. Clinical suspicion (the criteria below) should trigger urgent genetic testing rather than invasive investigation.^[1]

Major criteria:

• Family history of vEDS with a documented causative COL3A1 variant
• Arterial rupture at a young age
• Spontaneous sigmoid colon perforation (without diverticular disease or other bowel pathology)
• Uterine rupture in the third trimester (without previous caesarean) or severe peripartum perineal tears
• Carotid-cavernous sinus fistula (without trauma)

Minor criteria (2017 classification): easy bruising unrelated to trauma, thin translucent skin, characteristic facial features, spontaneous pneumothorax, acrogeria (aged appearance of hands), talipes equinovarus, congenital hip dislocation, small-joint hypermobility, tendon/muscle rupture, keratoconus, gingival recession and early-onset varicose veins

Other Ehlers-Danlos types: the 2017 classification recognises 13 types. This page focuses on vascular EDS, the type with the greatest arterial risk; the cardiovascular relevance of the others is summarised below.^[1][6]

• Hypermobile EDS: the commonest type, with no known gene and a clinical diagnosis. Mild aortic root dilatation and mitral valve prolapse are occasionally reported and are usually not progressive; orthostatic intolerance, including postural tachycardia syndrome, is common. A baseline echocardiogram is commonly performed, and a dilated or growing aorta should prompt a search for another diagnosis, such as Marfan or Loeys-Dietz syndrome.
• Classical EDS (COL5A1, COL5A2): skin hyperextensibility and atrophic scarring; arterial dissection or rupture is reported but rare
• COL1A1-related arterial fragility: specific COL1A1 variants (e.g. p.Arg312Cys) are associated with arterial dissection
• Kyphoscoliotic EDS (PLOD1, FKBP14): arterial rupture is reported
• Cardiac-valvular EDS (biallelic COL1A2): progressive, severe aortic and mitral valve disease

Genetic testing: COL3A1 sequencing (diagnostic; preferred over skin biopsy in the first instance)^[1]

Baseline arterial imaging: head-to-pelvis MR or CT angiography at diagnosis to document existing aneurysms, dissections and arterial tortuosity.^[3]

Surveillance imaging: Use non-invasive arterial imaging (duplex, CT or MR angiography) for surveillance at individualised intervals in expert care. Duplex ultrasound and MR angiography are preferred for repeated imaging to limit radiation. Avoid invasive arteriography and arterial puncture unless clinically essential, because COL3A1 disease carries a significant risk of arterial injury from invasive procedures^[2][3]

Echocardiography: aortic root and valves at baseline.^[3]

Blood pressure: measured at every visit, with home monitoring where helpful, since control is part of management.^[3]

Acute presentations: sudden severe pain in the abdomen, flank, chest or head needs urgent non-invasive imaging (CT angiography), which should not be withheld because of the fragility concerns that apply to invasive procedures.

1. General measures:

• Non-invasive arterial imaging (duplex / CT / MR angiography) of the whole arterial tree at individualised intervals^[3]
• Patient-held emergency/alert card; avoid contact and high-resistance sports; plan pregnancy and delivery at an expert centre (high risk of arterial and uterine rupture)
• Genetic counselling and family cascade testing, see the Genetic Testing page

2. Medical therapy:

1. Celiprolol: first-line; reduced arterial rupture/dissection in a randomised trial. Up-titrate to the maximum tolerated dose.^[4]
2. Strict blood-pressure control; avoid arterial puncture and elective angiography wherever possible.^[3]

3. Surgery:

• Avoid elective surgery where possible, tissue fragility makes haemostasis and repair difficult; conservative or endovascular management is preferred and should be at a centre familiar with vEDS^[3]

• Spontaneous arterial rupture or dissection: of medium-sized vessels, often without a preceding aneurysm, and the leading cause of death^[1]
• Hollow-organ rupture: sigmoid colon and gravid uterus, with spontaneous pneumothorax
• Catastrophic procedural and surgical bleeding: with poor wound healing, so intervention itself is hazardous
• High peripartum mortality.

Median survival: ~50 years

Pregnancy very high risk. Published mortality estimates vary; GeneReviews cites approximately 5% mortality per pregnancy, depending on variant, vascular history and expert management

mWHO class II–III or above: refer to a Pregnancy Heart Team before conception (see Pregnancy).

Based on ESC aortic-disease guidance and the celiprolol trial^[3][4].

Vascular EDS is managed in an expert centre; the intensity of surveillance is individualised to arterial history and variant.

Disclaimer: This table is general guidance based on published guidelines and does not replace clinical judgement. The responsible clinician is accountable for determining the appropriate, individualised follow-up plan for each patient.

• Arterial/bowel rupture can occur spontaneously without warning^[1]
• Avoid invasive vascular procedures when possible (tissue fragility)^[1]
• Do not delay urgent non-invasive imaging for acute pain
• Celiprolol reduced arterial events in a randomised trial: titrate to the maximum tolerated dose^[4]
• Most other EDS types carry much lower arterial risk; a progressive aortopathy in hypermobile EDS should prompt a search for another diagnosis^[6]
• Pregnancy is very high risk, not universally contraindicated; the largest series estimates ~5% maternal mortality per pregnancy, with roughly half of pregnancies having no major vascular complication; risk varies by COL3A1 variant and prior vascular history^[1]
• Offer early, non-directive, variant-informed reproductive counselling covering all options, including continuing pregnancy with specialist surveillance, surrogacy and adoption
• If pregnancy occurs: manage at a specialist centre; delivery timing and mode are set by the cardio-obstetric MDT
• Offer highly effective contraception (including LARC or sterilisation) to all women of reproductive age, with the decision led by the patient