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Pediatric Cardiology

, Volume 37, Issue 6, pp 1123–1126 | Cite as

Fibrillin-1 Gene Mutations in Left Ventricular Non-compaction Cardiomyopathy

  • John J. ParentEmail author
  • Jeffrey A. Towbin
  • John L. Jefferies
Original Article

Abstract

Left ventricular non-compaction cardiomyopathy (LVNC) is a unique cardiomyopathy with a current yield of about 30–40 % in identifying a causative gene mutation. A retrospective review of all patients with LVNC at our institution was performed and genetic testing was reviewed. Echocardiographic and cardiac magnetic resonance imaging was reviewed to corroborate the reported phenotype. We present a series of patients with LVNC dilated phenotype associated with fibrillin-1 gene mutations. Fifty-one patients were identified as having LVNC with reduced left ventricular function and/or left ventricular dilation. We retrospectively reviewed gene testing in this cohort when available and identified 5 patients (10 %) with an FBN1 gene mutation. Syndrome breakdown as follows: 3 with Marfan, 1 with Shprintzen-Goldberg, and 1 with no identifiable syndrome. Derangements in fibrillin-1 may impact the compaction process resulting in LVNC. Although causation has not been proven by our report, it certainly raises interest in a possible mechanistic relationship between fibrillin-1 and LVNC given the increased prevalence of Marfan syndrome and fibrillin-1 gene mutations in this cohort.

Keywords

Cardiomyopathy Left ventricular non-compaction Heart failure Fibrillin-1 Marfan syndrome 

Notes

Compliance with Ethical Standards

Conflict of interest

The authors have no conflicts of interest to disclose.

References

  1. 1.
    Towbin JA (2010) Left ventricular noncompaction: a new form of heart failure. Heart Fail Clin 4:453–469CrossRefGoogle Scholar
  2. 2.
    Jenni R, Oechslin EN, van der Loo B (2007) Isolated ventricular non-compaction of the myocardium in adults. Heart 93(1):11–15CrossRefPubMedGoogle Scholar
  3. 3.
    Jenni R, Oechslin E, Schneider J, Attenhofer Jost C, Kaufmann PA (2001) Echocardiographic and pathoanatomical characteristics of isolated left ventricular non-compaction: a step towards classification as a distinct cardiomyopathy. Heart 86:666–671CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Maron BJ, Towbin JA, Thiene G, Antzelevitch C, Corrado D, Arnett D, Moss AJ, Seidman CE, Young JB (2006) Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation 113:1807–1816CrossRefPubMedGoogle Scholar
  5. 5.
    Oeschslin E, Jenni R (2011) Left ventricular non-compaction revisited: a distinct phenotype with genetic heterogeneity? Eur Heart J 32(12):1446–1456CrossRefGoogle Scholar
  6. 6.
    Varnava AM (2001) Isolated left ventricular non-compaction: a distinct cardiomyopathy? Heart 86:599–600CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Zuckerman WA, Richmond ME, Singh RK, Carroll SJ, Starc TJ, Addonizio L (2011) Left-ventricular noncompaction in a pediatric population: predictors of survival. Pediatr Cardiol 32(4):406–412CrossRefPubMedGoogle Scholar
  8. 8.
    Brescia ST, Rosano JW, Pignatelli R, Jefferies JL, Price JF, Decker JA, Denfield SW, Dreyer WJ, Smith O, Towbin JA, Kim JJ (2013) Mortality and sudden death in pediatric left ventricular noncompaction in a tertiary referral center. Circulation 127(22):2202–2208CrossRefPubMedGoogle Scholar
  9. 9.
    Greutmann M, Mah ML, Silversides CK, Klaassen S, Attenhofer Jost CH, Jenni R, Oechslin EN (2012) Predictors of adverse outcome in adolescents and adults with isolated left ventricular noncompaction. Am J Cardiol 109(2):276–281CrossRefPubMedGoogle Scholar
  10. 10.
    Wald R, Veldtman G, Golding F, Kirsh J, McCrindle B, Benson L (2004) Determinants of outcome in isolated ventricular noncompaction in childhood. Am J Cardiol 94(12):1581–1584CrossRefPubMedGoogle Scholar
  11. 11.
    Tian T, Liu Y, Gao L, Wang J, Sun K, Zou Y, Wang L, Zhang L, Li Y, Xiao Y, Song L, Zhou X (2014) Isolated left ventricular noncompaction: clinical profile and prognosis in 106 adult patients. Heart Vessels 29(5):645–652CrossRefPubMedGoogle Scholar
  12. 12.
    Hoedenmaekers YM, Caliskan K, Michels M, Frohn-Mulder I, van der Smagt JJ, Phefferkorn JE, Wessels MW, ten Cate FJ, Sijbrands EJ, Dooijes D, Majoor-Krakauer DF (2010) The importance of genetic counseling, DNA diagnostics, and cardiologic family screening in left ventricular noncompaction cardiomyopathy. Circ Cardiovasc Genet 3(3):232–239CrossRefGoogle Scholar
  13. 13.
    Petersen SE, Selvanayagam JB, Wiesmann F, Robson MD, Francis JM, Anderson RH, Watkins H, Neubauer S (2005) Left ventricular non-compaction: insights from cardiovascular magnetic resonance imaging. J Am Coll Cardiol 46(1):101–105CrossRefPubMedGoogle Scholar
  14. 14.
    Kwiatkowski D, Hagenbuch S, Meyer R (2010) A teenager with Marfan syndrome and left ventricular noncompaction. Pediatr Cardiol 31(1):132–135CrossRefPubMedGoogle Scholar
  15. 15.
    Bouzeghrane F, Reihardt DP, Reudelhuber TL, Thibault G (2005) Enhanced expression of fibrillin-1, a constituent of the myocardial extracellular matrix in fibrosis. Am J Physiol Heart Circ Physiol 289(3):H982–H991CrossRefPubMedGoogle Scholar
  16. 16.
    Vracko R, Thorning D, Frederickson RG (1990) Spatial arrangements of microfibrils in myocardial scars: application of antibody to fibrillin. J Mol Cell Cardiol 22(7):749–757CrossRefPubMedGoogle Scholar
  17. 17.
    de Witte P, Aalberts JJ, Radonic T, Timmermans J, Scholte AJ, Zwinderman AH, Mulder BJ, Groenink M, van den Berg MP (2011) Intrinsic biventricular dysfunction in Marfan syndrome. Heart 97(24):2063–2068CrossRefPubMedGoogle Scholar
  18. 18.
    De Backer J (2009) The expanding cardiovascular phenotype of Marfan syndrome. Eur J Echocardiogr 10:213–215CrossRefPubMedGoogle Scholar
  19. 19.
    Lockhart M, Wirrig E, Phelps A, Wessels A (2011) Extracellular matrix and heart development. Birth Defects Res A Clin Mol Teratol 91(6):535–550CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Drechsler M, Schmidt AC, Meyer H, Paululat A (2013) The conserved ADAMTS-like protein lonely heart mediates matrix formation and cardiac tissue integrity. PLoS Genet 9(7):e1003616CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • John J. Parent
    • 1
    Email author
  • Jeffrey A. Towbin
    • 2
  • John L. Jefferies
    • 3
  1. 1.Riley Hospital for Children at Indiana University HealthIndiana University School of MedicineIndianapolisUSA
  2. 2.Division of Pediatric Cardiology, The Heart InstituteLe Bonheur Children’s HospitalMemphisUSA
  3. 3.The Heart InstituteCincinnati Children’s Hospital Medical CenterCincinnatiUSA

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