Marfan Syndrome


Marfan syndrome is a common autosomal dominant hereditary disorder of connective tissue with prominent manifestations in the eye, skeleton and cardiovascular system. Mutations in the gene for fibrillin‐1 (FBN1) can cause Marfan syndrome.

Keywords: Marfan syndrome; fibrillinopathy; microfibril; connective tissue; aortic dissection

Figure 1.

Diagram of a calcium‐binding epidermal growth factor‐like module (cbEGF). Fibrillin‐1 contains 43 cbEGF modules, which comprise about 42 amino acid residues with six cysteine residues (C) which together form three disulfide bonds in a 1–3, 2–4, 5–6 arrangement. cbEGF modules additionally contain a calcium‐binding consensus: D/N–X–D/N–E/Q–Xm–D/N*–Xn–Y/F (where m and n are variable and * indicates potential beta hydroxylation). (Figure modified from Robinson PN and Booms P (2001) Cellular and Molecular Life Sciences58: 1698–1707.)

Figure 2.

Domain organization of fibrillin‐1. Fourteen putative N‐glycosylation sites are shown as black dots above the protein, N‐ and C‐terminal proteolytic processing sites are shown as arrows and an RGD motif cell‐attachment signal is shown as an open triangle. EGF: epidermal growth factor; cbEGF: calcium‐binding epidermal growth factor‐like module; LTBP: latent transforming growth factor β1 binding protein (module also referred to as the TGFβ1bp). (Figure modified from Robinson PN and Booms P (2001) Cellular and Molecular Life Sciences58: 1698–1707.)

Figure 3.

Proposed dominant negative model of the pathogenesis of Marfan syndrome. Top: wild‐type (wt) fibrillin‐1 monomers polymerize with one another and with a series of other proteins to form aggregate structures called microfibrils. Bottom: a missense mutation (represented as an asterisk) is likely to alter the conformation of affected fibrillin‐1 monomers, which could interfere with polymerization, destabilize the polymeric microfibrils causing a progressive loss of microfibrils or otherwise interfere with proper microfibrillar function. (Figure modified from Robinson PN and Booms P (2001) Cellular and Molecular Life Sciences58: 1698–1707.)



De Paepe A, Devereux RB, Dietz HC, Hennekam RC and Pyeritz RE (1996) Revised diagnostic criteria for the Marfan syndrome. American Journal of Medical Genetics 62: 417–426.

Dietz HC, Cutting GR, Pyeritz RE, et al. (1991) Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature 352: 337–339.

Downing AK, Knott V, Werner JM, et al. (1996) Solution structure of a pair of calcium‐binding epidermal growth factor‐like domains: implications for the Marfan syndrome and other genetic disorders. Cell 85: 597–605.

Gott VL, Greene PS, Alejo DE, et al. (1999) Replacement of the aortic root in patients with Marfan's syndrome. New England Journal of Medicine 340: 1307–1313.

Pereira L, Lee SY, Gayraud B, et al. (1999) Pathogenetic sequence for aneurysm revealed in mice underexpressing fibrillin‐1. Proceedings of the National Academy of Sciences of the United States of America 96: 3819–3823.

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Reinhardt DP, Mechling DE, Boswell BA, et al. (1997) Calcium determines the shape of fibrillin. Journal of Biological Chemistry 272: 7368–7373.

Robinson PN and Booms P (2001) The molecular pathogenesis of the Marfan syndrome. Cellular and Molecular Life Sciences 58: 1698–1707.

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Further Reading

Handford PA (2000) Fibrillin‐1, a calcium binding protein of extracellular matrix. Biochimica et Biophysica Acta 1498: 84–90.

Pyeritz RE (2002) BR Marfan syndrome and other disorders of fibrillin. In: Rimoin DL, Connor JM, Pyeritz RE and Korf B (eds.) Emery and Rimoin's Principles and Practice of Medical Genetics, 4th ed., pp. 3977–4020. London, UK: Churchill Livingstone.

Ramirez F, Gayraud B and Pereira L (1999) Marfan syndrome: new clues to genotype–phenotype correlations. Annals of Medicine 31: 202–207.

Robinson PN and Godfrey M (2000) The molecular genetics of Marfan syndrome and related microfibrillopathies. Journal of Medical Genetics 37: 9–25.

Web Links

Online Mendelian Inheritance in Man: Marfan syndrome

Fibrillin‐1 (Marfan syndrome) (FBN1); Locus ID: 2200. LocusLink:

Fibrillin 2 (congenital contractural arachnodactyly) (FBN2); Locus ID: 2201. LocusLink:

Fibrillin‐1 (Marfan syndrome) (FBN1); MIM number: 134797. OMIM:

Fibrillin 2 (congenital contractural arachnodactyly) (FBN2); MIM number: 121050. OMIM:

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How to Cite close
Robinson, Peter N(Jan 2006) Marfan Syndrome. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0006087]