Skip to Main Content

We have a new app!

Take the Access library with you wherever you go—easy access to books, videos, images, podcasts, personalized features, and more.

Download the Access App here: iOS and Android

Key Points

  • Disease summary:

    • Marfan syndrome (MFS) is a relatively common heritable disorder of connective tissue that affects many tissues and organs, most prominently the ocular, cardiovascular, and musculoskeletal systems. The natural history predicts early demise, typically from aortic dissection. However, advances in medical and surgical management over the past three decades have extended life expectancy to near normal.

  • Hereditary basis:

    • MFS is an autosomal dominant condition found in all populations. Reproduction is affected in the most severe cases, so sporadic cases represent one-quarter to one-third of all cases. Most cases (>95%) are due to mutations in FBN1, the product of which is a large glycoprotein in the extracellular matrix, especially elastic fibers. The molecule also functions to stabilize the latent transforming growth factor beta (TGFβ) complex, so the pathogenesis to an important extent involves excess canonical and noncanonical signaling.

    • MFS shows no ethnic predilection and occurs at a prevalence of at least 1 per 3 to 5000.

  • Differential diagnosis:

    • A number of syndromes include ectopia lentis, including an autosomal dominant form due to mutations in FBN1 with mild MFS-like skeletal features but no involvement of the aorta.

    • Isolated dilatation of the aortic root can occur in the absence of other features of MFS. Dilatation of the ascending aorta, typically of the mid portion more than the sinuses, often accompanies a bicuspid aortic valve. Dilatation, dissection, or both of any portion of the aorta can be inherited as an autosomal dominant trait and can be due to mutations in a growing list of genes (FBN1, TGFBR1, TGFBR2, ACTA2, MY11, SMAD3, COL3A1).

    • Many individuals have some features of MFS but fail to meet the revised Ghent criteria. If the individual is a child, then features sufficient to diagnose MFS may emerge with time, and a diagnosis of emerging MFS is useful to ensure that routine follow-up is maintained. Other individuals never warrant a diagnosis of MFS, despite having numerous, mild features. A diagnosis of MASS phenotype is appropriate for the individual with several of the following: mitral valve prolapse (MVP), myopia, an aortic root at the upper limits of normal, mild skeletal features, and striae distensae. This phenotype is of unclear molecular cause, can be inherited as an autosomal dominant trait, and, importantly, is not generally associated with progressive aortic dilatation or dissection.

    • In the Loeys-Dietz syndrome (LDS), the aorta and its branches are tortuous from an early age and the aorta tends to dissect at a smaller diameter than in MFS. The craniofacial characteristics include cleft palate or bifid uvula, craniosynostosis, and increased head circumference. The lens of the eye does not dislocate in LDS. Molecular testing for mutations in TGFBR1 and TGFBR2 can distinguish LDS from MFS.

Diagnostic Criteria and Clinical Characteristics

Diagnostic Criteria for MFS

The revised Ghent criteria have been expanded ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.