Marfan Syndrome

  • Francesco RamirezEmail author
  • Julie De Backer


Marfan syndrome is a heritable connective tissue disease with typical impairment of multiple organ systems. The condition is primarily caused by mutations in the fibrillin 1 gene. The diagnosis is based on the demonstration of clinical manifestations and is often complicated by several factors, including age-dependent expression, the important inter- and intrafamilial variability, and overlap with other connective tissue disorders and disorders of the aorta, which are discussed in this chapter. Additional molecular genetic testing may be useful / necessary in certain cases to confirm the diagnosis as illustrated in the cases presented. We will also review the molecular aspects of the disorder with particular emphasis on the different structural and functional roles of fibrillin 1 assemblies. Finally, we will discuss the current concepts of treatment for Marfan syndrome.


Dissecting aneurysm Fibrillin 1 Marfan syndrome Mechanosensing TGFβ signaling 


  1. Chen X et al (2013) Conundrum of angiotensin II and TGF-β interactions in aortic aneurysms. Curr Opin Pharmacol 13:180–185CrossRefGoogle Scholar
  2. Cook JR et al (2014) Abnormal muscle mechanosignaling triggers cardiomyopathy in mice with Marfan syndrome. J Clin Invest 124:1329–1339PubMedPubMedCentralGoogle Scholar
  3. Cook JR et al (2015) Dimorphic effects of TGFβ signaling during aortic aneurysm progression in mice suggest a combinatorial therapy for Marfan syndrome. Arterioscler Thromb Vasc Biol 35:911–917CrossRefGoogle Scholar
  4. den Hartog AW et al (2016) The effect of losartan therapy on ventricular function in Marfan patients with haploinsufficient or dominant negative FBN1 mutations. Neth Hear J 24:675–681CrossRefGoogle Scholar
  5. Devereux RB et al (2012) Normal limits in relation to age, body size and gender of two-dimensional echocardiographic aortic root dimensions in persons ≥15 years of age. Am J Cardiol 110:1189–1194CrossRefGoogle Scholar
  6. Habashi JP et al (2006) Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science 312:117–121CrossRefGoogle Scholar
  7. Judge DP, Dietz HC (2005) Marfan’s syndrome. Lancet 366:1965–1976CrossRefGoogle Scholar
  8. Li W et al (2014) Tgfbr2 disruption in postnatal smooth muscle impairs aortic wall homeostasis. J Clin Invest 124:755–767CrossRefGoogle Scholar
  9. Loeys BL et al (2006) Aneurysm syndromes caused by mutations in the TGF-b receptor. N Engl J Med 355:788–798CrossRefGoogle Scholar
  10. Loeys BL et al (2010a) The revised Ghent nosology for the Marfan syndrome. J Med Genet 47:476–485CrossRefGoogle Scholar
  11. Loeys BL et al (2010b) Mutations in fibrillin-1 cause congenital scleroderma: stiff skin syndrome. Sci Transl Med 2:23ra20CrossRefGoogle Scholar
  12. Milewicz DM, Regalado ES (2015) Use of genetics for personalized management of heritable thoracic aortic disease: how do we get there? J Thorac Cardiovasc Surg 149:S3–S5CrossRefGoogle Scholar
  13. Milewicz DM et al (2010) De novo ACTA2 mutation causes a novel syndrome of multisystemic smooth muscle dysfunction. Am J Med Genet A 152A:2437–2443CrossRefGoogle Scholar
  14. Milewicz DM et al (2017) Altered smooth muscle cell force generation as a driver of thoracic aortic aneurysm and dissections. Arterioscler Thromb Vasc Biol 37:26–34CrossRefGoogle Scholar
  15. Pitcher A et al (2015) Design and rationale of a prospective, collaborative meta-analysis of all randomized controlled trials of angiotensin receptor antagonists in Marfan syndrome, based on individual patient data: a report from the Marfan Treatment Trialists’ Collaboration. Am Heart J 169:605–612CrossRefGoogle Scholar
  16. Pyeritz RE (2014) Heritable thoracic aortic disorders. Curr Opin Cardiol 29:97–102CrossRefGoogle Scholar
  17. Robertson IB, Rifkin DB (2016) Regulation of the bioavailability of TGF-b and TGF-b-related proteins. Cold Spring Harb Perspect Biol 8(6):a021907CrossRefGoogle Scholar
  18. Sakai LY et al (2016) FBN1: the disease-causing gene for Marfan syndrome and other genetic disorders. Gene 591:279–291CrossRefGoogle Scholar
  19. van de Laar IM et al (2011) Mutations in SMAD3 cause a syndromic form of aortic aneurysm and dissections with early-onset osteoarthritis. Nat Genet 43:121–126CrossRefGoogle Scholar
  20. Wagenseil JE, Mecham RP (2009) Vascular extracellular matrix and arterial mechanics. Physiol Rev 89:957–989CrossRefGoogle Scholar

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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of Pharmacological SciencesIcahn School of Medicine at Mount SinaiNew YorkUSA
  2. 2.Department of Cardiology and Center for Medical GeneticsGhent University HospitalGhentBelgium

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