FBN1 mutations in patients with descending thoracic aortic dissections

Am J Med Genet A. 2010 Feb;152A(2):413-6. doi: 10.1002/ajmg.a.32856.

Abstract

Aortic aneurysm and dissection cause significant morbidity and mortality. There are several known single gene disorders that predispose to isolated aortic disease and eventually aneurysm and dissection. FBN1 mutations are associated with multiple clinical phenotypes, including Marfan syndrome (MFS), MASS phenotype, and familial ectopia lentis, but rarely with isolated aortic aneurysm and dissection. In this report, we describe three patients who presented with primary descending thoracic aortic dissection and who were found to have an FBN1 mutation. None of the patients fulfilled clinical criteria for the diagnosis of MFS, and all had few or none of the skeletal features typical of the condition. Two patients had a history of long-term hypertension, and such a history was suspected in the third patient. These observations suggest that some individuals with FBN1 mutations have significant aortic disease involvement of other systems that is typical of FBN1 mutation-related syndromes. Superimposed risk factors, such as hypertension, may weaken the aortic wall and eventually lead to aortic dissection. Given that the cost continues to decrease, we suggest that diagnostic DNA sequencing for FBN1 mutations in patients with thoracic aortic aneurysms and dissection may be a practical clinical step in evaluating such patients and at-risk family members.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aneurysm, Dissecting / diagnosis
  • Aneurysm, Dissecting / genetics*
  • Aorta, Thoracic / pathology*
  • Aortic Aneurysm, Thoracic / diagnosis
  • Aortic Aneurysm, Thoracic / genetics*
  • DNA Mutational Analysis
  • Female
  • Fibrillin-1
  • Fibrillins
  • Humans
  • Hypertension / pathology
  • Male
  • Microfilament Proteins / genetics*
  • Middle Aged
  • Mutation*
  • Phenotype
  • Risk Factors
  • Sequence Analysis, DNA

Substances

  • FBN1 protein, human
  • Fibrillin-1
  • Fibrillins
  • Microfilament Proteins