Skip to main content
NCBI home page
Archives of Disease in Childhood logoLink to Archives of Disease in Childhood
. 2001 Feb;84(2):129–137. doi: 10.1136/adc.84.2.129

Natural history of cardiovascular manifestations in Marfan syndrome

C D M van Karnebeek 1, M Naeff 1, B Mulder 1, R Hennekam 1, M Offringa 1
PMCID: PMC1718664  PMID: 11159287

Abstract

AIMS—To investigate the natural history of mitral valve and aortic abnormalities in patients with Marfan syndrome during childhood and adolescence.
METHODS—Fifty two patients with Marfan syndrome were followed for a mean of 7.9 years. Occurrence of adverse cardiovascular outcomes was measured clinically and by ultrasound examination.
RESULTS—Mitral valve prolapse (MVP) was diagnosed in 46 patients at a mean age of 9.7 years, more than 80% of whom presented as "silent MVP". Mitral regurgitation (MR) occurred in 25 patients, aortic dilatation in 43, and aortic regurgitation (AR) in 13. Both MVP and aortic dilatation developed at a constant rate during the age period 5-20 years. In 23 patients MVP was diagnosed before aortic dilatation, in 18 the reverse occurred, and in 11 patients the two abnormalities were diagnosed simultaneously. During follow up, 21 patients showed progression of mitral valve dysfunction; progression of aortic abnormalities occurred in 13. Aortic surgery was performed in 10; two died of subsequent complications. Mitral valve surgery was performed in six. In sporadic female Marfan patients the age at initial diagnosis of MVP, MR, aortic dilatation, and AR was lowest, the grade of MR and AR most severe, the time lapse between the occurrence of MVP and subsequent MR as well as between dilatation and subsequent AR shortest, and the risk for cardiovascular associated morbidity and mortality highest.
CONCLUSIONS—During childhood and adolescence in Marfan syndrome, mitral valve dysfunction as well as aortic abnormalities develop and progress gradually, often without symptoms, but may cause considerable morbidity and mortality by the end of the second decade, especially in female sporadic patients.



Full Text

The Full Text of this article is available as a PDF (136.1 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beighton P., de Paepe A., Danks D., Finidori G., Gedde-Dahl T., Goodman R., Hall J. G., Hollister D. W., Horton W., McKusick V. A. International Nosology of Heritable Disorders of Connective Tissue, Berlin, 1986. Am J Med Genet. 1988 Mar;29(3):581–594. doi: 10.1002/ajmg.1320290316. [DOI] [PubMed] [Google Scholar]
  2. Brown O. R., DeMots H., Kloster F. E., Roberts A., Menashe V. D., Beals R. K. Aortic root dilatation and mitral valve prolapse in Marfan's syndrome: an ECHOCARDIOgraphic study. Circulation. 1975 Oct;52(4):651–657. doi: 10.1161/01.cir.52.4.651. [DOI] [PubMed] [Google Scholar]
  3. Brown O. R., DeMots H., Kloster F. E., Roberts A., Menashe V. D., Beals R. K. Aortic root dilatation and mitral valve prolapse in Marfan's syndrome: an ECHOCARDIOgraphic study. Circulation. 1975 Oct;52(4):651–657. doi: 10.1161/01.cir.52.4.651. [DOI] [PubMed] [Google Scholar]
  4. De Paepe A., Devereux R. B., Dietz H. C., Hennekam R. C., Pyeritz R. E. Revised diagnostic criteria for the Marfan syndrome. Am J Med Genet. 1996 Apr 24;62(4):417–426. doi: 10.1002/(SICI)1096-8628(19960424)62:4<417::AID-AJMG15>3.0.CO;2-R. [DOI] [PubMed] [Google Scholar]
  5. Dietz H. C., Cutting G. R., Pyeritz R. E., Maslen C. L., Sakai L. Y., Corson G. M., Puffenberger E. G., Hamosh A., Nanthakumar E. J., Curristin S. M. Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature. 1991 Jul 25;352(6333):337–339. doi: 10.1038/352337a0. [DOI] [PubMed] [Google Scholar]
  6. Fleischer K. J., Nousari H. C., Anhalt G. J., Stone C. D., Laschinger J. C. Immunohistochemical abnormalities of fibrillin in cardiovascular tissues in Marfan's syndrome. Ann Thorac Surg. 1997 Apr;63(4):1012–1017. doi: 10.1016/s0003-4975(97)00061-1. [DOI] [PubMed] [Google Scholar]
  7. Geva T., Hegesh J., Frand M. The clinical course and echocardiographic features of Marfan's syndrome in childhood. Am J Dis Child. 1987 Nov;141(11):1179–1182. doi: 10.1001/archpedi.1987.04460110049020. [DOI] [PubMed] [Google Scholar]
  8. Geva T., Hegesh J., Frand M. The clinical course and echocardiographic features of Marfan's syndrome in childhood. Am J Dis Child. 1987 Nov;141(11):1179–1182. doi: 10.1001/archpedi.1987.04460110049020. [DOI] [PubMed] [Google Scholar]
  9. Geva T., Sanders S. P., Diogenes M. S., Rockenmacher S., Van Praagh R. Two-dimensional and Doppler echocardiographic and pathologic characteristics of the infantile Marfan syndrome. Am J Cardiol. 1990 May 15;65(18):1230–1237. doi: 10.1016/0002-9149(90)90979-b. [DOI] [PubMed] [Google Scholar]
  10. Geva T., Sanders S. P., Diogenes M. S., Rockenmacher S., Van Praagh R. Two-dimensional and Doppler echocardiographic and pathologic characteristics of the infantile Marfan syndrome. Am J Cardiol. 1990 May 15;65(18):1230–1237. doi: 10.1016/0002-9149(90)90979-b. [DOI] [PubMed] [Google Scholar]
  11. Gillinov A. M., Zehr K. J., Redmond J. M., Gott V. L., Deitz H. C., Reitz B. A., Laschinger J. C., Cameron D. E. Cardiac operations in children with Marfan's syndrome: indications and results. Ann Thorac Surg. 1997 Oct;64(4):1140–1145. doi: 10.1016/s0003-4975(97)00849-7. [DOI] [PubMed] [Google Scholar]
  12. Gillinov A. M., Zehr K. J., Redmond J. M., Gott V. L., Deitz H. C., Reitz B. A., Laschinger J. C., Cameron D. E. Cardiac operations in children with Marfan's syndrome: indications and results. Ann Thorac Surg. 1997 Oct;64(4):1140–1145. doi: 10.1016/s0003-4975(97)00849-7. [DOI] [PubMed] [Google Scholar]
  13. Gray J. R., Bridges A. B., West R. R., McLeish L., Stuart A. G., Dean J. C., Porteous M. E., Boxer M., Davies S. J. Life expectancy in British Marfan syndrome populations. Clin Genet. 1998 Aug;54(2):124–128. doi: 10.1111/j.1399-0004.1998.tb03714.x. [DOI] [PubMed] [Google Scholar]
  14. Haycock G. B., Schwartz G. J., Wisotsky D. H. Geometric method for measuring body surface area: a height-weight formula validated in infants, children, and adults. J Pediatr. 1978 Jul;93(1):62–66. doi: 10.1016/s0022-3476(78)80601-5. [DOI] [PubMed] [Google Scholar]
  15. Kainulainen K., Pulkkinen L., Savolainen A., Kaitila I., Peltonen L. Location on chromosome 15 of the gene defect causing Marfan syndrome. N Engl J Med. 1990 Oct 4;323(14):935–939. doi: 10.1056/NEJM199010043231402. [DOI] [PubMed] [Google Scholar]
  16. Krivokapich J., Child J. S., Dadourian B. J., Perloff J. K. Reassessment of echocardiographic criteria for diagnosis of mitral valve prolapse. Am J Cardiol. 1988 Jan 1;61(1):131–135. doi: 10.1016/0002-9149(88)91318-5. [DOI] [PubMed] [Google Scholar]
  17. Legget M. E., Unger T. A., O'Sullivan C. K., Zwink T. R., Bennett R. L., Byers P. H., Otto C. M. Aortic root complications in Marfan's syndrome: identification of a lower risk group. Heart. 1996 Apr;75(4):389–395. doi: 10.1136/hrt.75.4.389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lipscomb K. J., Clayton-Smith J., Harris R. Evolving phenotype of Marfan's syndrome. Arch Dis Child. 1997 Jan;76(1):41–46. doi: 10.1136/adc.76.1.41. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Magenis R. E., Maslen C. L., Smith L., Allen L., Sakai L. Y. Localization of the fibrillin (FBN) gene to chromosome 15, band q21.1. Genomics. 1991 Oct;11(2):346–351. doi: 10.1016/0888-7543(91)90142-2. [DOI] [PubMed] [Google Scholar]
  20. Marsalese D. L., Moodie D. S., Vacante M., Lytle B. W., Gill C. C., Sterba R., Cosgrove D. M., Passalacqua M., Goormastic M., Kovacs A. Marfan's syndrome: natural history and long-term follow-up of cardiovascular involvement. J Am Coll Cardiol. 1989 Aug;14(2):422–431. doi: 10.1016/0735-1097(89)90197-6. [DOI] [PubMed] [Google Scholar]
  21. McKUSICK V. A. The cardiovascular aspects of Marfan's syndrome: a heritable disorder of connective tissue. Circulation. 1955 Mar;11(3):321–342. doi: 10.1161/01.cir.11.3.321. [DOI] [PubMed] [Google Scholar]
  22. Miyatake K., Izumi S., Okamoto M., Kinoshita N., Asonuma H., Nakagawa H., Yamamoto K., Takamiya M., Sakakibara H., Nimura Y. Semiquantitative grading of severity of mitral regurgitation by real-time two-dimensional Doppler flow imaging technique. J Am Coll Cardiol. 1986 Jan;7(1):82–88. doi: 10.1016/s0735-1097(86)80263-7. [DOI] [PubMed] [Google Scholar]
  23. Murdoch J. L., Walker B. A., Halpern B. L., Kuzma J. W., McKusick V. A. Life expectancy and causes of death in the Marfan syndrome. N Engl J Med. 1972 Apr 13;286(15):804–808. doi: 10.1056/NEJM197204132861502. [DOI] [PubMed] [Google Scholar]
  24. Pan C. W., Chen C. C., Wang S. P., Hsu T. L., Chiang B. N. Echocardiographic study of cardiac abnormalities in families of patients with Marfan's syndrome. J Am Coll Cardiol. 1985 Nov;6(5):1016–1020. doi: 10.1016/s0735-1097(85)80303-x. [DOI] [PubMed] [Google Scholar]
  25. Pini R., Roman M. J., Kramer-Fox R., Devereux R. B. Mitral valve dimensions and motion in Marfan patients with and without mitral valve prolapse. Comparison to primary mitral valve prolapse and normal subjects. Circulation. 1989 Oct;80(4):915–924. doi: 10.1161/01.cir.80.4.915. [DOI] [PubMed] [Google Scholar]
  26. Pyeritz R. E., Wappel M. A. Mitral valve dysfunction in the Marfan syndrome. Clinical and echocardiographic study of prevalence and natural history. Am J Med. 1983 May;74(5):797–807. doi: 10.1016/0002-9343(83)91070-7. [DOI] [PubMed] [Google Scholar]
  27. Roberts W. C. Congenital cardiovascular abnormalities usually "silent" until adulthood: morphologic features of the floppy mitral valve, valvular aortic stenosis, discrete subvalvular aortic stenosis, hypertrophic cardiomyopathy, sinus of Valsalva aneurysm, and the Marfan syndrome. Cardiovasc Clin. 1979;10(1):407–453. [PubMed] [Google Scholar]
  28. Roman M. J., Devereux R. B., Kramer-Fox R., O'Loughlin J. Two-dimensional echocardiographic aortic root dimensions in normal children and adults. Am J Cardiol. 1989 Sep 1;64(8):507–512. doi: 10.1016/0002-9149(89)90430-x. [DOI] [PubMed] [Google Scholar]
  29. Roman M. J., Rosen S. E., Kramer-Fox R., Devereux R. B. Prognostic significance of the pattern of aortic root dilation in the Marfan syndrome. J Am Coll Cardiol. 1993 Nov 1;22(5):1470–1476. doi: 10.1016/0735-1097(93)90559-j. [DOI] [PubMed] [Google Scholar]
  30. Shores J., Berger K. R., Murphy E. A., Pyeritz R. E. Progression of aortic dilatation and the benefit of long-term beta-adrenergic blockade in Marfan's syndrome. N Engl J Med. 1994 May 12;330(19):1335–1341. doi: 10.1056/NEJM199405123301902. [DOI] [PubMed] [Google Scholar]
  31. Silverman D. I., Burton K. J., Gray J., Bosner M. S., Kouchoukos N. T., Roman M. J., Boxer M., Devereux R. B., Tsipouras P. Life expectancy in the Marfan syndrome. Am J Cardiol. 1995 Jan 15;75(2):157–160. doi: 10.1016/s0002-9149(00)80066-1. [DOI] [PubMed] [Google Scholar]
  32. Silverman D. I., Burton K. J., Gray J., Bosner M. S., Kouchoukos N. T., Roman M. J., Boxer M., Devereux R. B., Tsipouras P. Life expectancy in the Marfan syndrome. Am J Cardiol. 1995 Jan 15;75(2):157–160. doi: 10.1016/s0002-9149(00)80066-1. [DOI] [PubMed] [Google Scholar]
  33. Tsang V. T., Pawade A., Karl T. R., Mee R. B. Surgical management of Marfan syndrome in children. J Card Surg. 1994 Jan;9(1):50–54. doi: 10.1111/j.1540-8191.1994.tb00823.x. [DOI] [PubMed] [Google Scholar]

Articles from Archives of Disease in Childhood are provided here courtesy of BMJ Publishing Group

RESOURCES