Vascular Ehlers-Danlos Syndrome (vEDS)

Vascular Ehlers-Danlos Syndrome (vEDS)

Description

Ehlers-Danlos syndrome (EDS) is an inherited disorder caused by mutations in the genes responsible for the structure, production, or processing of collagen, an important component of the connective tissues in the human body, or proteins that interact with collagen. EDS is a spectrum disorder where patients present with various forms, the most serious of which is vEDS, also known as EDS type IV, which is generally caused by a mutation in the COL3A1 gene. vEDS causes abnormal fragility in blood vessels, which can give rise to aneurysms, abnormal connections between blood vessels known as arteriovenous fistulas, arterial dissections, and spontaneous vascular ruptures, all of which can be potentially life-threatening. Gastrointestinal and uterine fragility or rupture also commonly occur in vEDS patients. Spontaneous arterial rupture has a peak incidence in the third or fourth decade of life in vEDS patients but may occur earlier and is the most common cause of sudden death in vEDS patients. Arterial rupture or dissection events occur in about 25% of patients before the age of 20 but increase to roughly 90% of patients by the age of 40. The median survival age of vEDS patients in the U.S. is 51 years, with arterial rupture being the most common cause of sudden death.1

Epidemiology

Studies estimate the prevalence of vEDS as ranging from approximately 1 in 90,000 to 1 in 250,000.2 In 2017, we commissioned a patient-finder study that phenotypically identified 4,169 vEDS patients in the United States from an analysis of a commercially available patient claims database, with data of approximately 190 million unique patient lives. Based on that information, we estimate the prevalence of phenotypically-defined vEDS in the United States could be greater than 1 in 45,000.

Diagnosis

vEDS should be suspected in the presence of the following major symptoms:4,5

  • Characteristic facial features (thin lips, narrow nose, undersized jaw, protruding eyes)
  • Easy bruising
  • Thin skin with visible veins (especially on the chest or abdomen)
  • Rupture or tearing of the arteries, intestines or uterus
  • Family history of vEDS

Other less obvious symptoms that may also help raise suspicion of vEDS include:3,4

  • Acrogeria (an aged appearance, especially of the hands and feet)
  • Carotid-cavernous sinus arteriovenous fistula (an abnormal connection between an artery in the neck and a set of veins behind the eye)
  • Joint hypermobility
  • Rupture of muscles or tendons
  • Early-onset varicose veins
  • Collapsed lung (with possible buildup of blood in the chest cavity)
  • Chronic joint dislocations
  • Dislocated hips or clubfoot (in infants born with the disorder)
  • Receding gums

Clinical suspicion of vEDS is confirmed through genetic testing of COL3A1 and/or biochemical analysis of fibroblasts, the cells that produce collagen, as a means of detecting abnormalities in type III collagen.2,5

Management

Despite the serious nature of vEDS, there are no approved pharmacologic treatments for these patients, and current treatment and intervention is limited to asymptomatic periodic monitoring to assess for aneurysms and other arterial events, precautionary measures (e.g., modulating lifestyle to minimize injury and treating any existing hypertension), genetic counseling, and surgery when needed (Byers 2017; Germain 2006). Surgery may be required urgently to treat potentially fatal complications such as uncontrolled hemorrhage, or a very large or rapidly-expanding aneurysm (Germain 2006; Oderich 2005). Despite surgical precautions, including delicate and atraumatic handling of tissues and choosing the least complex and most direct repair technique possible (Germain 2002), a number of patients develop post-operative hemorrhagic complications, as well as problems relating to anastomosis of prosthetic grafts (Oderich 2005). Although surgery is potentially an option for some patients in some situations, risk for complications is high and inevitable, and with limited success.

References:

  1. Pepin M, et al. Clinical and genetic features of Ehlers-Danlos syndrome type IV, the vascular type. N Engl J Med. 2000;342:673-80.
  2. Byers PH et al. Am J Med Genet Part C Semin Med Genet. 2017;175C:40-47.
  3. Malfait F et al. Am J Med Genet Part C Semin Med Genet. 2017;175C:8-26.
  4. Beighton P, et al. Am J Med Genet. 1998;77:31-37.
  5. Lum YW et al. Curr Opin Cardiol. 2011;26:494-501.
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