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Marfan syndrome

Abstract

Marfan syndrome (MFS) is an autosomal dominant, age-related but highly penetrant condition with substantial intrafamilial and interfamilial variability. MFS is caused by pathogenetic variants in FBN1, which encodes fibrillin-1, a major structural component of the extracellular matrix that provides support to connective tissues, particularly in arteries, the pericondrium and structures in the eye. Up to 25% of individuals with MFS have de novo variants. The most prominent manifestations of MFS are asymptomatic aortic root aneurysms, aortic dissections, dislocation of the ocular lens (ectopia lentis) and skeletal abnormalities that are characterized by overgrowth of the long bones. MFS is diagnosed based on the Ghent II nosology; genetic testing confirming the presence of a FBN1 pathogenetic variant is not always required for diagnosis but can help distinguish MFS from other heritable thoracic aortic disease syndromes that can present with skeletal features similar to those in MFS. Untreated aortic root aneurysms can progress to life-threatening acute aortic dissections. Management of MFS requires medical therapy to slow the rate of growth of aneurysms and decrease the risk of dissection. Routine surveillance with imaging techniques such as transthoracic echocardiography, CT or MRI is necessary to monitor aneurysm growth and determine when to perform prophylactic repair surgery to prevent an acute aortic dissection.

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Fig. 1: Aortic root aneurysm and acute aortic dissections in patients with MFS.
Fig. 2: Pathogenetic variants in FBN1.
Fig. 3: Role of fibrillin-1 in the aorta.
Fig. 4: Clinical manifestations of Marfan syndrome.
Fig. 5: Imaging for thoracic aortic disease in individuals with MFS.

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Acknowledgements

NIH R01HL109942 and R01HL146583, American Heart Association Merit Award, Genetic Aortic Disorders Association Canada, John Ritter Foundation, Marfan Foundation to D.M.M. The authors thank the patients with Marfan syndrome who shared their story.

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Introduction (D.M.M. and R.E.P.); Epidemiology (D.M.M. and R.E.P.); Mechanisms/pathophysiology (D.M.M., C.B. and R.E.P.); Diagnosis, screening and prevention (D.M.M., A.C.B., J.De B., S.A.M., G.J., A.E. and R.E.P.); Management (D.M.M., A.C.B., S.A.M., I.H.M., G.J., A.E. and R.E.P.); Quality of life (D.M.M. and R.E.P.); Outlook (D.M.M.); Overview of Primer (D.M.M.).

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Correspondence to Dianna M. Milewicz.

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Nature Reviews Disease Primers thanks M. Groenink; D. Reinhardt, who co-reviewed with R. Zhang; P. Robinson; L. Sakai; and Y. Von Kodolitsch for their contribution to the peer review of this work.

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Milewicz, D.M., Braverman, A.C., De Backer, J. et al. Marfan syndrome. Nat Rev Dis Primers 7, 64 (2021). https://doi.org/10.1038/s41572-021-00298-7

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