Vascular Ehlers-Danlos Syndrome (vEDS)

Vascular Ehlers-Danlos Syndrome (vEDS)

Description

Vascular Ehlers-Danlos syndrome (vEDS, EDS type IV) constitutes < 5% of all cases of EDS (Bergqvist 2013) and is considered the most serious subtype, as it is associated with a high risk of death due to arterial, intestinal, and uterine ruptures, as well as complications of surgical and radiologic interventions (Germain 2006). Patients with vEDS have a median survival of 51 years (Pepin 2014). While the first complications and diagnosis can occur as early as infancy, most patients do not have a complication (or receive a diagnosis) until their 20s or 30s, which often initially presents as life-threatening dissections or ruptures; complications affect 25% of patients before the age of 20 and 80% by the age of 40 (Pepin 2000).

Most patients with vEDS are asymptomatic and remain undiagnosed until they present with clinically important life-threatening complications (Beridze 2012; Pepin 2014; Shalhub 2014). Diagnosis of vEDS is therefore typically made based on clinical signs and presentation, after which patients undergo molecular testing for genetic confirmation. After the “index” case is diagnosed, some patients and families decide to undergo cascade screening which can reveal additional confirmed vEDS patients. Additionally, approximately 50% of vEDS patients have inherited mutations and 50% have spontaneous mutations (Shalhub 2014).

Epidemiology

Studies estimate the prevalence of vEDS as ranging from approximately 1 in 90,000 to 1 in 250,000.1 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:4,5

  • 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.1,2

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. Byers PH et al. Am J Med Genet Part C Semin Med Genet. 2017;175C:40-47.
  2. Lum YW et al. Curr Opin Cardiol. 2011;26:494-501.
  3. 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.
  4. Malfait F et al. Am J Med Genet Part C Semin Med Genet. 2017;175C:8-26.
  5. Beighton P, et al. Am J Med Genet. 1998;77:31-37.
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