Marfan syndrome is a multisystem disorder of connective tissue that is inherited in an autosomal dominant fashion, and results from mutation of the FBN1 gene on human chromosome 15.
There are a number of conditions of the connective tissue with a similar phenotype that can be confused with Marfan syndrome. Modifications of the diagnostic criteria have recently been published, facilitating the differentiation of Marfan syndrome from these conditions.
It is still difficult to use modern genetic testing for diagnosis because Marfan syndrome can be caused by many different mutations in FBN1, a large gene with 65 coding segments, while mutations in other genes can cause overlapping phenotypes.
Several clinical trials of drug therapy, including the antihypertensive drug losartan, are in progress.
- 1. Summers KM, West JA, Peterson MM, et al. Challenges in the diagnosis of Marfan syndrome. Med J Aust 2006; 184: 627-631. <MJA full text>
- 2. De Paepe A, Devereux RB, Dietz HC, et al. Revised diagnostic criteria for the Marfan syndrome. Am J Med Genet 1996; 62: 417-426.
- 3. Loeys BL, Dietz HC, Braverman AC, et al. The revised Ghent nosology for the Marfan syndrome. J Med Genet 2010; 47: 476-485.
- 4. Faivre L, Collod-Beroud G, Adès L, et al. The new Ghent criteria for Marfan syndrome: what do they change? Clin Genet 2012; 81: 433-442.
- 5. Roman MJ, Devereux RB, Kramer-Fox R, O’Loughlin J. Two-dimensional echocardiographic aortic root dimensions in normal children and adults. Am J Cardiol 1989; 64: 507-512.
- 6. Charbonneau NL, Carlson EJ, Tufa S, et al. In vivo studies of mutant fibrillin-1 microfibrils. J Biol Chem 2010; 285: 24943-24955.
- 7. Neptune ER, Frischmeyer PA, Arking DE, et al. Dysregulation of TGF-beta activation contributes to pathogenesis in Marfan syndrome. Nat Genet 2003; 33: 407-411.
- 8. Loeys BL, Chen J, Neptune ER, et al. A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat Genet 2005; 37: 275-281.
- 9. Habashi JP, Judge DP, Holm TM, et al. Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science 2006; 312: 117-121.
- 10. Nistala H, Lee-Arteaga S, Carta L, et al. Differential effects of alendronate and losartan therapy on osteopenia and aortic aneurysm in mice with severe Marfan syndrome. Hum Mol Genet 2010; 19: 4790-4798.
- 11. Davis MR, Summers KM. Structure and function of the mammalian fibrillin gene family: implications for human connective tissue diseases. Mol Genet Metab 2012; Aug 3. [Epub ahead of print.]
- 12. Yetman AT, Bornemeier RA, McCrindle BW. Long-term outcome in patients with Marfan syndrome: is aortic dissection the only cause of sudden death? J Am Coll Cardiol 2003; 41: 329-332.
- 13. Bowne SJ, Sullivan LS, Koboldt DC, et al. Identification of disease-causing mutations in autosomal dominant retinitis pigmentosa (adRP) using next-generation DNA sequencing. Invest Ophthalmol Vis Sci 2011; 52: 494-503.
- 14. Hedges DJ, Guettouche T, Yang S, et al. Comparison of three targeted enrichment strategies on the SOLiD sequencing platform. PLoS One 2011; 6: e18595.
- 15. Ku CS, Naidoo N, Pawitan Y. Revisiting Mendelian disorders through exome sequencing. Hum Genet 2011; 129: 351-370.
- 16. De Leeneer K, Hellemans J, De Schrijver J, et al. Massive parallel amplicon sequencing of the breast cancer genes BRCA1 and BRCA2: opportunities, challenges, and limitations. Hum Mutat 2011; 32: 335-344.
- 17. Faivre L, Masurel-Paulet A, Collod-Béroud G, et al. Clinical and molecular study of 320 children with Marfan syndrome and related type I fibrillinopathies in a series of 1009 probands with pathogenic FBN1 mutations. Pediatrics 2009; 123: 391-398.
- 18. Baetens M, Van Laer L, De Leeneer K, et al. Applying massive parallel sequencing to molecular diagnosis of Marfan and Loeys-Dietz syndromes. Hum Mutat 2011; 32: 1053-1062.
- 19. Ozsolak F, Milos PM. RNA sequencing: advances, challenges and opportunities. Nat Rev Genet 2011; 12: 87-98.
- 20. Tang N, Suthers G. FBN1. In: Tang N, Suthers G, editors. RCPA [Royal College of Pathologists of Australasia] Catalogue of Genetic Tests and Laboratories. April 2009. http://genetictesting.rcpa.edu.au/component/gene/genetest/FBN1/ (accessed May 2012).
- 21. NCBI, GeneTests. Marfan syndrome. [Online database] http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/clinical_disease_id/2104?db=genetests (accessed May 2012).
- 22. Summers KM, Xu D, West JA, et al. An integrated approach to management of Marfan syndrome caused by an FBN1 exon 18 mutation in an Australian Aboriginal family. Clin Genet 2004; 65: 66-69.
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