Pediatric Cardiology

, Volume 34, Issue 4, pp 991–998

Impact of Age and Gender on Cardiac Pathology in Children and Adolescents With Marfan Syndrome

  • Goetz C. Mueller
  • Veronika Stark
  • Kristoffer Steiner
  • Yskert von Kodolitsch
  • Meike Rybczynski
  • Jochen Weil
  • Thomas S. Mir
Original Article


Cardiac pathologies are the major aspect in the treatment strategies for Marfan syndrome (MFS). In this progressive disease, less is known about manifestations and progression of cardiovascular symptoms in children. To define a certain decision regarding therapeutic options, knowledge concerning the onset of cardiovascular findings is essential. From 1998 to 2011, suspected pediatric Marfan patients were subjected to a standardized diagnostic program. Cardiovascular findings were analyzed in terms of age at first clinical manifestation, prevalence and gender differences, morbidity, mortality, and treatment. Marfan syndrome was diagnosed in 82 patients (46 boys; mean age at diagnosis, 9.0 ± 5.7 years). At first presentation, aortic root dilation was found in 56 % of patients, mitral valve prolapse in 31 %, whereas pulmonary artery dilation was detected in 22 % and tricuspid valve prolapse in only 17 % of patients. Aortic (2.5 %) and mitral valve regurgitations (22 %) are significantly correlated with aortic root dilation (p < 0.01) and mitral valve prolapse (p < 0.05) but without relevant progression during childhood. Prophylactic medication was initiated for 42 % of the patients (mean age, 8.0 ± 4.5 years) because of progressive aortic root dilation. Aortic dissection did not appear. Aortic root surgery was needed for 4 % of the patients. Gender-specific differences in cardiovascular findings, progression of disease, or treatment did not appear. Comparable with adults, aortic root dilation is the most frequent cardiovascular finding in children and associated with relevant morbidity, whereas aortic and mitral valve regurgitation are of minor clinical relevance. Manifestation at an early age and slow progression of cardiovascular findings underscore the necessity of repeated echocardiographic examinations for early diagnosis and start of prophylactic treatment.


Cardiovascular manifestation Marfan syndrome Morbidity Pediatric 


  1. 1.
    Ammash NM, Sundt TM, Connolly HM (2008) Marfan syndrome: diagnosis and management. Curr Probl Cardiol 33:7–39PubMedCrossRefGoogle Scholar
  2. 2.
    Avierinos JF, Detaint D, Messika-Zeitoun D, Mohty D, Enriquez-Sarano M (2008) Risk, determinants, and outcome implications of progression of mitral regurgitation after diagnosis of mitral valve prolapse in a single community. Am J Cardiol 101:662–667PubMedCrossRefGoogle Scholar
  3. 3.
    De Paepe A, Devereux RB, Dietz HC, Hennekam RC, Pyeritz RE (1996) Revised diagnostic criteria for the Marfan syndrome. Am J Med Genet 62:417–426PubMedCrossRefGoogle Scholar
  4. 4.
    Dean JC (2007) Marfan syndrome: clinical diagnosis and management. Eur J Hum Genet 15:724–733PubMedCrossRefGoogle Scholar
  5. 5.
    Detaint D, Faivre L, Collod-Beroud G et al (2010) Cardiovascular manifestations in men and women carrying a FBN1 mutation. Eur Heart J 31:2223–2229PubMedCrossRefGoogle Scholar
  6. 6.
    Dietz HC, Cutting GR, Pyeritz RE et al (1991) Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature 352:337–339PubMedCrossRefGoogle Scholar
  7. 7.
    Faivre L, Collod-Beroud G, Child A et al (2008) Contribution of molecular analyses in diagnosing Marfan syndrome and type I fibrillinopathies: an international study of 1,009 probands. J Med Genet 45:384–390PubMedCrossRefGoogle Scholar
  8. 8.
    Fleischer KJ, Nousari HC, Anhalt GJ, Stone CD, Laschinger JC (1997) Immunohistochemical abnormalities of fibrillin in cardiovascular tissues in Marfan’s syndrome. Ann Thorac Surg 63:1012–1017PubMedCrossRefGoogle Scholar
  9. 9.
    Freed LA, Benjamin EJ, Levy D et al (2002) Mitral valve prolapse in the general population: the benign nature of echocardiographic features in the Framingham Heart Study. J Am Coll Cardiol 40:1298–1304PubMedCrossRefGoogle Scholar
  10. 10.
    Hokken RB, Bartelings MM, Bogers AJJC, GittenbergerdeGroot AC (1997) Morphology of the pulmonary and aortic roots with regard to the pulmonary autograft procedure. J Thorac Cardiovasc Surg 113:453–461PubMedCrossRefGoogle Scholar
  11. 11.
    Judge DP, Dietz HC (2005) Marfan’s syndrome. Lancet 366:1965–1976PubMedCrossRefGoogle Scholar
  12. 12.
    Kampmann C, Wiethoff CM, Wenzel A et al (2000) Normal values of M-mode echocardiographic measurements of more than 2,000 healthy infants and children in central Europe. Heart 83:667–672PubMedCrossRefGoogle Scholar
  13. 13.
    Ladouceur M, Fermanian C, Lupoglazoff JM et al (2007) Effect of beta-blockade on ascending aortic dilatation in children with the Marfan syndrome. Am J Cardiol 99:406–409PubMedCrossRefGoogle Scholar
  14. 14.
    Loeys B, Nuytinck L, Delvaux I, De Bie S, De Paepe A (2001) Genotype and phenotype analysis of 171 patients referred for molecular study of the fibrillin-1 gene FBN1 because of suspected Marfan syndrome. Arch Intern Med 161:2447–2454PubMedCrossRefGoogle Scholar
  15. 15.
    Loeys BL, Dietz HC, Braverman AC et al (2010) The revised Ghent nosology for the Marfan syndrome. J Med Genet 47:476–485PubMedCrossRefGoogle Scholar
  16. 16.
    McKusick KV (1955) The cardiovascular aspects of Marfan’s syndrome: a heritable disorder of connective tissue. Circulation 11:321–342PubMedCrossRefGoogle Scholar
  17. 17.
    Meijboom LJ, Timmermans J, Zwinderman AH, Engelfriet PM, Mulder BJ (2005) Aortic root growth in men and women with the Marfan’s syndrome. Am J Cardiol 96:1441–1444PubMedCrossRefGoogle Scholar
  18. 18.
    Miyatake K, Izumi S, Okamoto M et al (1986) Semiquantitative grading of severity of mitral regurgitation by real-time two-dimensional Doppler flow imaging technique. J Am Coll Cardiol 7:82–88PubMedCrossRefGoogle Scholar
  19. 19.
    Nistri S, Porciani MC, Attanasio M, Abbate R, Gensini GF, Pepe G (2012) Association of Marfan syndrome and bicuspid aortic valve: frequency and outcome. Int J Cardiol 155:324–325PubMedCrossRefGoogle Scholar
  20. 20.
    Nollen GJ, van Schijndel KE, Timmermans J, et al (2002) Pulmonary artery root dilatation in Marfan syndrome: quantitative assessment of an unknown criterion. Heart 87(5):470–471Google Scholar
  21. 21.
    Okura H, Takada Y, Yamabe A et al (2011) Prevalence and correlates of physiological valvular regurgitation in healthy subjects. Circ J 75:2699–2704PubMedCrossRefGoogle Scholar
  22. 22.
    Pini R, Roman MJ, Kramer-Fox R, Devereux RB (1989) Mitral valve dimensions and motion in Marfan patients with and without mitral valve prolapse: comparison to primary mitral valve prolapse and normal subjects. Circulation 80:915–924PubMedCrossRefGoogle Scholar
  23. 23.
    Pyeritz RE, McKusick VA (1979) The Marfan syndrome: diagnosis and management. N Engl J Med 300:772–777PubMedCrossRefGoogle Scholar
  24. 24.
    Roman MJ, Devereux RB, Kramer-Fox R, O’Loughlin J (1989) Two-dimensional echocardiographic aortic root dimensions in normal children and adults. Am J Cardiol 64:507–512PubMedCrossRefGoogle Scholar
  25. 25.
    Rybczynski M, Bernhardt AM, Rehder U et al (2008) The spectrum of syndromes and manifestations in individuals screened for suspected Marfan syndrome. Am J Med Genet A 146A:3157–3166PubMedCrossRefGoogle Scholar
  26. 26.
    Rybczynski M, Treede H, Sheikhzadeh S et al (2011) Predictors of outcome of mitral valve prolapse in patients with the Marfan syndrome. Am J Cardiol 107:268–274PubMedCrossRefGoogle Scholar
  27. 27.
    Senbaklavaci O, Kaneko Y, Bartunek A et al (2001) Rupture and dissection in pulmonary artery aneurysms: incidence, cause, and treatment: review and case report. J Thorac Cardiovasc Surg 121:1006–1008PubMedCrossRefGoogle Scholar
  28. 28.
    Shores J, Berger KR, Murphy EA, Pyeritz RE (1994) Progression of aortic dilatation and the benefit of long-term beta-adrenergic blockade in Marfan’s syndrome. N Engl J Med 330:1335–1341PubMedCrossRefGoogle Scholar
  29. 29.
    Siu SC, Silversides CK (2010) Bicuspid aortic valve disease. J Am Coll Cardiol 55:2789–2800PubMedCrossRefGoogle Scholar
  30. 30.
    Zoghbi WA, Enriquez-Sarano M, Foster E et al (2003) Recommendations for evaluation of the severity of native valvular regurgitation with two-dimensional and Doppler echocardiography. J Am Soc Echocardiogr 16:777–802PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Goetz C. Mueller
    • 1
  • Veronika Stark
    • 1
  • Kristoffer Steiner
    • 1
  • Yskert von Kodolitsch
    • 2
  • Meike Rybczynski
    • 2
  • Jochen Weil
    • 1
  • Thomas S. Mir
    • 1
  1. 1.Clinic for Pediatric CardiologyUniversity Heart Centre Hamburg-EppendorfHamburgGermany
  2. 2.Clinic for CardiologyUniversity Heart Centre HamburgHamburgGermany

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