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Relationship between fibrillin-1 genotype and severity of cardiovascular involvement in Marfan syndrome

Romy Franken1,2, Gisela Teixido-Tura1, Maria Brion3

  • 1Servei de Cardiologia, Unitat de Marfan, Hospital Universitari, Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.

Heart (British Cardiac Society)
|May 5, 2017
PubMed
Abstract

Insights

Patients with haploinsufficiency (HI) FBN1 mutations in Marfan syndrome experience more severe aortic dilation and a higher risk of dissection or death compared to those with dominant negative (DN) FBN1 mutations.

Area of Science:

  • Cardiovascular Medicine
  • Genetics
  • Marfan Syndrome Research

Background:

  • The impact of FBN1 mutation type on cardiovascular manifestations in Marfan syndrome (MFS) remains debated.
  • FBN1 mutations are classified as dominant negative (DN) or haploinsufficiency (HI).

Purpose of the Study:

  • To investigate the influence of FBN1 mutation type (DN vs. HI) on aortic dimensions and dilation rates.
  • To assess the effect of FBN1 mutation type on cardiovascular events, including aortic dissection and mortality in MFS patients.

Main Methods:

  • Compared aortic diameters and dilation rates in MFS patients with HI-FBN1 versus DN-FBN1 mutations.
  • Utilized echocardiography to measure aortic dimensions and tracked clinical endpoints like dissection and death.
  • Classified FBN1 mutations based on their effect on fibrillin-1 protein in the extracellular matrix.

Main Results:

  • Patients with HI-FBN1 mutations exhibited larger baseline aortic root diameters compared to DN-FBN1 patients.
  • A significantly faster rate of aortic root and ascending aorta dilation was observed in the HI-FBN1 group.
  • The HI-FBN1 group showed a trend towards increased risk for combined aortic dissection and death events.

Conclusions:

  • Haploinsufficiency (HI) FBN1 mutations are associated with a more severe aortic phenotype in Marfan syndrome.
  • HI mutations lead to larger aortic diameters and accelerated dilation, increasing the risk of dissection and mortality compared to dominant negative (DN) mutations.
Keywords:
FBN1Marfan syndromeaortic dilationaortic dissectionhaploinsufficiency

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