Prevalence of dural ectasia in 63 gene-mutation-positive patients with features of Marfan syndrome type 1 and Loeys-Dietz syndrome and report of 22 novel FBN1 mutations

Clin Genet. 2009 Mar;75(3):265-70. doi: 10.1111/j.1399-0004.2008.01126.x. Epub 2009 Jan 20.

Abstract

Marfan syndrome is an autosomal dominant disorder involving different organ systems. Marfan syndrome type 1 (MFS1) is caused by mutations in the FBN1 gene. Heterozygosity for mutations in the TGFBR1 or TGFBR2 genes cause Loeys-Dietz syndrome (LDS) types 2A and 2B that overlap with MFS1 in their clinical features. The phenotype of MFS1 is defined by the Ghent nosology, which classifies the clinical manifestations in major and minor criteria. Dural ectasia is one of the major criteria for Marfan syndrome but it is rarely tested for. We here report 22 novel and 9 recurrent mutations in the FBN1 gene in 36 patients with clinical features of Marfan syndrome. Sixty patients with identified mutations in the FBN1 gene and three patients with mutations in the TGFBR1 or TGFBR2 genes were examined for dural ectasia. Forty-seven of the 60 patients (78%) with MFS1 showed the dural ectasia criterion and 13 (22%) did not. Thirty-three (55%) patients were suspected of having Marfan syndrome and 24 (73%) of them had dural ectasia. Two of the three patients with LDS had dural ectasia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aortic Aneurysm, Thoracic / genetics
  • Dilatation, Pathologic / epidemiology
  • Dilatation, Pathologic / genetics
  • Dura Mater / abnormalities*
  • Female
  • Fibrillin-1
  • Fibrillins
  • Humans
  • Male
  • Marfan Syndrome / classification
  • Marfan Syndrome / diagnosis
  • Marfan Syndrome / genetics*
  • Microfilament Proteins / genetics*
  • Microfilament Proteins / metabolism
  • Middle Aged
  • Mutation*
  • Prevalence
  • Protein Serine-Threonine Kinases / genetics
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / genetics
  • Syndrome

Substances

  • FBN1 protein, human
  • Fibrillin-1
  • Fibrillins
  • Microfilament Proteins
  • Receptors, Transforming Growth Factor beta
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptor, Transforming Growth Factor-beta Type II
  • TGFBR1 protein, human