Spontaneous pneumothorax and hemothorax frequently precede the arterial and intestinal complications of vascular Ehlers-Danlos syndrome

Am J Med Genet A. 2019 May;179(5):797-802. doi: 10.1002/ajmg.a.61094. Epub 2019 Feb 22.


Vascular Ehlers-Danlos syndrome (vEDS) is a connective tissue disorder due to defective type III collagen production and is associated with arterial rupture, spontaneous intestinal perforation, and gravid uterine rupture. Spontaneous pneumothorax and/or hemothorax (P/HTX) also occurs in vEDS patients. The temporal relation of pulmonary manifestations to arterial and intestinal complications in vEDS has not been well described. This was investigated in a multi-institutional retrospective case series of vEDS patients with confirmatory testing for COL3A1 mutation between 2000 and 2012. Data abstracted included demographics, family histories, presentation, and management of associated complications. Ninety-six cases (39% males, mean age 38.6 ± 15.5 years, range 8-79) had confirmatory testing for vEDS. P/HTX was documented in 17 (17.7%) cases. Most P/HTX preceded the diagnosis of vEDS (81%). Diagnosis of vEDS was made after arterial or intestinal complications at a mean of 7 years (range 0-26) post the initial P/HTX. In conclusion, spontaneous P/HTX is an early manifestation of vEDS frequently preceding an arterial complication or intestinal perforation. Thus, a spontaneous P/HTX in a young patient should trigger a differential diagnosis that includes vEDS. This should lead to an investigation of other vEDS features and subsequent genetic testing if vEDS features are present.

Keywords: Ehlers-Danlos syndrome type IV; spontaneous hemothorax; spontaneous pneumothorax; type III collagen; vascular Ehlers-Danlos syndrome.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Collagen Type III / genetics
  • Cross-Sectional Studies
  • Ehlers-Danlos Syndrome / complications*
  • Ehlers-Danlos Syndrome / diagnosis
  • Ehlers-Danlos Syndrome / genetics*
  • Female
  • Genetic Association Studies
  • Genetic Testing
  • Hemothorax / diagnosis
  • Hemothorax / etiology*
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Phenotype*
  • Pneumothorax / diagnosis
  • Pneumothorax / etiology*
  • Prevalence
  • Young Adult


  • COL3A1 protein, human
  • Collagen Type III