Skip to main content
SpringerLink
Log in

Noncompaction Cardiomyopathy in Childhood

  • Chapter
  • First Online:
Noncompaction Cardiomyopathy

  • 378 Accesses

Abstract

Noncompaction cardiomyopathy (NCCM), also called left ventricular noncompaction (LVNC), a classified form of cardiomyopathy, is a genetic disease characterized by excessive and unusual trabeculations within the mature left ventricle (LV). NCCM has been considered to be a developmental failure of the heart to form fully the compact myocardium during the later stages of cardiac development. Clinically and pathologically, NCCM is characterized by a spongy morphological appearance of the myocardium occurring primarily in the LV with the abnormal trabeculations typically being most evident in the apical and midlateral-inferior portions of the LV. The right ventricle (RV) may also be affected alone or in conjunction with the LV. In NCCM, in addition to the regional presence of prominent trabeculae and inter-trabecular recesses in the LV, thickening of the myocardium in 2 distinct layers composed of compacted and non-compacted myocardium is also classically noted. It may be associated with left ventricular dilation or hypertrophy, systolic and/or diastolic dysfunction, atrial enlargement, or various forms of congenital heart disease. The myocardium in NCCM may demonstrate normal or abnormal systolic or diastolic function and the size, thickness or function may change unexpectedly (“undulating phenotype”). Affected individuals are at risk of left or right ventricular failure, or both. Heart failure symptoms can be exercise-induced or persistent at rest, but many patients are asymptomatic. Chronically treated patients sometimes present acutely with decompensated heart failure. Other life-threatening risks are ventricular arrhythmias and atrioventricular block, presenting clinically as syncope, and sudden death. Genetic inheritance arises in at least 30–50% of patients, NCCM is thought to occur in approximately 1 per 7000 live births. It occurs in newborns, young children and adults, with the worst reported outcomes seen in infants, particularly those with associated systemic disease and metabolic derangement. In some families, a consistent phenotype of NCCM is seen in affected relatives but quite commonly individuals with features of NCCM are found in families where other affected relatives have typical hypertrophic cardiomyopathy, dilated cardiomyopathy, or restrictive cardiomyopathy. Mutations in ~15 genes have been implicated and include cytoskeletal, sarcomeric, and ion channel genes, with sarcomere-encoding genes being most common. In the case of NCCM with congenital heart disease, disturbance of the Notch or Wnt signaling pathways appear to be part of a “final common pathway” for this form of the disease. In addition, disrupted mitochondrial function and metabolic abnormalities have a causal role as well. Treatments focus on improvement of cardiac efficiency and reduction of mechanical stress in those with systolic dysfunction. Further, arrhythmia therapy and implantation of an automatic implantable cardioverter-defibrillator (ICD) for prevention of sudden death are mainstays of treatment when deemed necessary and appropriate. Patients with NCCM associated with congenital heart disease commonly require surgical or catheter-based interventions. Despite progress in diagnosis and treatment over the past 10–15 years, understanding of the disorder and outcomes continue to need further improvement.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 54.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 69.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 99.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Grant RT. An unusual anomaly of the coronary vessels in the malformed heart of a child. Heart. 1926;13:273–83.

    Google Scholar 

  2. Chin TK, Perloff JK, Williams RG, Jue K, Mohrmann R. Isolated noncompaction of left ventricular myocardium. A study of eight cases. Circulation. 1990;82:507–13.

    Article  CAS  PubMed  Google Scholar 

  3. Pignatelli RH, McMahon CJ, Dreyer WJ, et al. Clinical characterization of left ventricular noncompaction in children: a relatively common form of cardiomyopathy. Circulation. 2003;108:2672–8.

    Article  PubMed  Google Scholar 

  4. Engberding R, Yelbuz TM, Breithardt G. Isolated noncompaction of the left ventricular myocardium -- a review of the literature two decades after the initial case description. Clin Res Cardiol. 2007;96:481–8.

    Article  CAS  PubMed  Google Scholar 

  5. Sedmera D, Pexieder T, Vuillemin M, Thompson RP, Anderson RH. Developmental patterning of the myocardium. Anat Rec. 2000;258:319–37.

    Article  CAS  PubMed  Google Scholar 

  6. Dusek J, Ostadal B, Duskova M. Postnatal persistence of spongy myocardium with embryonic blood supply. Arch Pathol. 1975;99:312–7.

    CAS  PubMed  Google Scholar 

  7. Fazio G, Lunetta M, Grassedonio E, et al. Noncompaction of the right ventricle. Pediatr Cardiol. 2010;31:576–8.

    Article  PubMed  Google Scholar 

  8. Ranganathan A, Ganesan G, Sangareddi V, Pillai AP, Ramasamy A. Isolated noncompaction of right ventricle--a case report. Echocardiography. 2012;29:E169–72.

    Article  PubMed  Google Scholar 

  9. Tigen K, Karaahmet T, Gurel E, Cevik C, Basaran Y. Biventricular noncompaction: a case report. Echocardiography. 2008;25:993–6.

    Article  PubMed  Google Scholar 

  10. Towbin JA. Left ventricular noncompaction: a new form of heart failure. Heart Fail Clin. 2010;6:453–69.

    Article  PubMed  Google Scholar 

  11. Maron BJ, Towbin JA, Thiene G, et al. 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. 2006;113:1807–16.

    Article  PubMed  Google Scholar 

  12. Stollberger C, Finsterer J, Blazek G. Left ventricular hypertrabeculation/noncompaction and association with additional cardiac abnormalities and neuromuscular disorders. Am J Cardiol. 2002;90:899–902.

    Article  PubMed  Google Scholar 

  13. Stollberger C, Finsterer J. Left ventricular hypertrabeculation/noncompaction. J Am Soc Echocardiogr. 2004;17:91–100.

    Article  PubMed  Google Scholar 

  14. Ichida F, Hamamichi Y, Miyawaki T, et al. Clinical features of isolated noncompaction of the ventricular myocardium: long-term clinical course, hemodynamic properties, and genetic background. J Am Coll Cardiol. 1999;34:233–40.

    Article  CAS  PubMed  Google Scholar 

  15. Cartoni D, Salvini P, De Rosa R, Cortese A, Nazzaro MS, Tanzi P. Images in cardiovascular medicine. Multiple coronary artery-left ventricle microfistulae and spongy myocardium: the eagerly awaited link? Circulation. 2007;116:e81–4.

    Article  PubMed  Google Scholar 

  16. Reynen K, Bachmann K, Singer H. Spongy myocardium. Cardiology. 1997;88:601–2.

    Article  CAS  PubMed  Google Scholar 

  17. Icardo JM, Fernandez-Teran A. Morphologic study of ventricular trabeculation in the embryonic chick heart. Acta Anat. 1987;130:264–74.

    Article  CAS  PubMed  Google Scholar 

  18. Chen H, Zhang W, Li D, Cordes TM, Payne RM, Shou W. Analysis of ventricular hypertrabeculation and noncompaction using genetically engineered mouse models. Pediatr Cardiol. 2009;30:626–34.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Harvey RP. Patterning the vertebrate heart. Nat Rev Genet. 2002;3:544–56.

    Article  CAS  PubMed  Google Scholar 

  20. Risebro CA, Riley PR. Formation of the ventricles. Sci World J. 2006;6:1862–80.

    Article  Google Scholar 

  21. Sedmera D, McQuinn T. Embryogenesis of the heart muscle. Heart Fail Clin. 2008;4:235–45.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Yang J, Bucker S, Jungblut B, et al. Inhibition of Notch2 by Numb/Numblike controls myocardial compaction in the heart. Cardiovasc Res. 2012;96:276–85.

    Article  CAS  PubMed  Google Scholar 

  23. Ichida F, Tsubata S, Bowles KR, et al. Novel gene mutations in patients with left ventricular noncompaction or Barth syndrome. Circulation. 2001;103:1256–63.

    Article  CAS  PubMed  Google Scholar 

  24. Caliskan K, Ujvari B, Bauernfeind T, et al. The prevalence of early repolarization in patients with noncompaction cardiomyopathy presenting with malignant ventricular arrhythmias. J Cardiovasc Electrophysiol. 2012;23:938–44.

    Article  PubMed  Google Scholar 

  25. Steffel J, Duru F. Rhythm disorders in isolated left ventricular noncompaction. Ann Med. 2012;44:101–8.

    Article  PubMed  Google Scholar 

  26. Attenhofer Jost CH, Connolly HM, Warnes CA, et al. Noncompacted myocardium in Ebstein’s anomaly: initial description in three patients. J Am Soc Echocardiogr. 2004;17:677–80.

    Article  PubMed  Google Scholar 

  27. Zuckerman WA, Richmond ME, Singh RK, Carroll SJ, Starc TJ, Addonizio LJ. Left-ventricular noncompaction in a pediatric population: predictors of survival. Pediatr Cardiol. 2011;32:406–12.

    Article  PubMed  Google Scholar 

  28. Stahli BE, Gebhard C, Biaggi P, et al. Left ventricular non-compaction: Prevalence in congenital heart disease. Int J Cardiol. 2013;167:2477–81.

    Article  PubMed  Google Scholar 

  29. Madan S, Mandal S, Bost JE, et al. Noncompaction cardiomyopathy in children with congenital heart disease: evaluation using cardiovascular magnetic resonance imaging. Pediatr Cardiol. 2012;33:215–21.

    Article  PubMed  Google Scholar 

  30. Scaglia F, Towbin JA, Craigen WJ, et al. Clinical spectrum, morbidity, and mortality in 113 pediatric patients with mitochondrial disease. Pediatrics. 2004;114:925–31.

    Article  PubMed  Google Scholar 

  31. Yaplito-Lee J, Weintraub R, Jamsen K, Chow CW, Thorburn DR, Boneh A. Cardiac manifestations in oxidative phosphorylation disorders of childhood. J Pediatr. 2007;150:407–11.

    Article  CAS  PubMed  Google Scholar 

  32. Pepper MS. Transforming growth factor-beta: vasculogenesis, angiogenesis, and vessel wall integrity. Cytokine Growth Factor Rev. 1997;8:21–43.

    Article  CAS  PubMed  Google Scholar 

  33. Suri C, Jones PF, Patan S, et al. Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell. 1996;87:1171–80.

    Article  CAS  PubMed  Google Scholar 

  34. Ferrara N, Carver-Moore K, Chen H, et al. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature. 1996;380:439–42.

    Article  CAS  PubMed  Google Scholar 

  35. Zhang W, Chen H, Wang Y, Yong W, Zhu W, Liu Y, Wagner GR, Payne RM, Field LJ, Xin H, Cai CL, Shou W. Tbx20 transcription factor is a downstream mediator for bone morphogenetic protein-10 in regulating cardiac ventricular wall development and function. J Biol Chem. 2011;286(42):36820–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Stollberger C, Blazek G, Dobias C, Hanafin A, Wegner C, Finsterer J. Frequency of stroke and embolism in left ventricular hypertrabeculation/noncompaction. Am J Cardiol. 2011;108:1021–3.

    Article  PubMed  Google Scholar 

  37. Greutmann M, Mah ML, Silversides CK, et al. Predictors of adverse outcome in adolescents and adults with isolated left ventricular noncompaction. Am J Cardiol. 2012;109:276–81.

    Article  PubMed  Google Scholar 

  38. Steffel J, Kobza R, Oechslin E, Jenni R, Duru F. Electrocardiographic characteristics at initial diagnosis in patients with isolated left ventricular noncompaction. Am J Cardiol. 2009;104:984–9.

    Article  PubMed  Google Scholar 

  39. Celiker A, Ozkutlu S, Dilber E, Karagoz T. Rhythm abnormalities in children with isolated ventricular noncompaction. Pacing Clin Electrophysiol. 2005;28:1198–202.

    Article  PubMed  Google Scholar 

  40. Ritter M, Oechslin E, Sutsch G, Attenhofer C, Schneider J, Jenni R. Isolated noncompaction of the myocardium in adults. Mayo Clin Proc. 1997;72:26–31.

    Article  CAS  PubMed  Google Scholar 

  41. Aras D, Tufekcioglu O, Ergun K, et al. Clinical features of isolated ventricular noncompaction in adults long-term clinical course, echocardiographic properties, and predictors of left ventricular failure. J Card Fail. 2006;12:726–33.

    Article  PubMed  Google Scholar 

  42. Sandhu R, Finkelhor RS, Gunawardena DR, Bahler RC. Prevalence and characteristics of left ventricular noncompaction in a community hospital cohort of patients with systolic dysfunction. Echocardiography. 2008;25:8–12.

    PubMed  Google Scholar 

  43. Kovacevic-Preradovic T, Jenni R, Oechslin EN, Noll G, Seifert B, Attenhofer Jost CH. Isolated left ventricular noncompaction as a cause for heart failure and heart transplantation: a single center experience. Cardiology. 2009;112:158–64.

    Article  CAS  PubMed  Google Scholar 

  44. Patrianakos AP, Parthenakis FI, Nyktari EG, Vardas PE. Noncompaction myocardium imaging with multiple echocardiographic modalities. Echocardiography. 2008;25:898–900.

    Article  PubMed  Google Scholar 

  45. Ronderos R, Avegliano G, Borelli E, Kuschnir P, Castro F, Sanchez G, Perea G, Corneli M, Zanier MM, Andres S, Aranda A, Conde D, Trivi M. Estimation of prevalence of the left ventricular noncompaction among adults. Am J Cardiol. 2016;118(6):901–5.

    Article  PubMed  Google Scholar 

  46. Sarma RJ, Chana A, Elkayam U. Left ventricular noncompaction. Prog Cardiovasc Dis. 2010;52:264–73.

    Article  PubMed  Google Scholar 

  47. Niemann M, Stork S, Weidemann F. Left ventricular noncompaction cardiomyopathy: an overdiagnosed disease. Circulation. 2012;126:e240-3.

    Article  PubMed  Google Scholar 

  48. Murphy RT, Thaman R, Blanes JG, et al. Natural history and familial characteristics of isolated left ventricular non-compaction. Eur Heart J. 2005;26:187–92.

    Article  PubMed  Google Scholar 

  49. Bhatia NL, Tajik AJ, Wilansky S, Steidley DE, Mookadam F. Isolated noncompaction of the left ventricular myocardium in adults: a systematic overview. J Card Fail. 2011;17:771–8.

    Article  PubMed  Google Scholar 

  50. Brescia ST, Rossano JW, Pignatelli R, et al. Mortality and sudden death in pediatric left ventricular noncompaction in a tertiary referral center. Circulation. 2013;127:2202–8.

    Article  PubMed  Google Scholar 

  51. Caliskan K, Kardos A, Szili-Torok T. Empty handed: a call for an international registry of risk stratification to reduce the ‘sudden-ness’ of death in patients with non-compaction cardiomyopathy. Europace. 2009;11:1138–9.

    Article  PubMed  Google Scholar 

  52. Biagini E, Ragni L, Ferlito M, et al. Different types of cardiomyopathy associated with isolated ventricular noncompaction. Am J Cardiol. 2006;98:821–4.

    Article  PubMed  Google Scholar 

  53. Ergul Y, Nisli K, Varkal MA, et al. Electrocardiographic findings at initial diagnosis in children with isolated left ventricular noncompaction. Ann Noninvasive Electrocardiol. 2011;16:184–91.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Onay OS, Yildirim I, Beken B, et al. Successful implantation of an intracardiac defibrillator in an infant with long QT syndrome and isolated noncompaction of the ventricular myocardium. Pediatr Cardiol. 2013;34:189–93.

    Article  PubMed  Google Scholar 

  55. Nakashima K, Kusakawa I, Yamamoto T, et al. A left ventricular noncompaction in a patient with long QT syndrome caused by a KCNQ1 mutation: a case report. Heart Vessel. 2013;28:126–9.

    Article  Google Scholar 

  56. Nascimento BR, Vidigal DF, Carneiro RD, et al. Complete atrioventricular block as the first manifestation of noncompaction of the ventricular myocardium. Pacing Clin Electrophysiol. 2013;36:e107–10.

    Article  PubMed  Google Scholar 

  57. Ulusoy RE, Kucukarslan N, Kirilmaz A, Demiralp E. Noncompaction of ventricular myocardium involving both ventricles. Eur J Echocardiogr. 2006;7:457–60.

    Article  PubMed  Google Scholar 

  58. Williams T, Machann W, Kuhler L, Hamm H, Müller-Höcker J, Zimmer M, Ertl G, Ritter O, Beer M, Schönberger J. Novel desmoplakin mutation: juvenile biventricular cardiomyopathy with left ventricular non-compaction and acantholytic palmoplantar keratoderma. Clin Res Cardiol. 2011;100:1087–93.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Wlodarska EK, Wozniak O, Konka M, Piotrowska-Kownacka D, Walczak E, Hoffman P. Isolated ventricular noncompaction mimicking arrhythmogenic right ventricular cardiomyopathy--a study of nine patients. Int J Cardiol. 2010;145:107–11.

    Article  PubMed  Google Scholar 

  60. Hughes ML, Carstensen B, Wilkinson JL, Weintraub RG. Angiographic diagnosis, prevalence and outcomes for left ventricular noncompaction in children with congenital cardiac disease. Cardiol Young. 2007;17:56–63.

    Article  PubMed  Google Scholar 

  61. Jenni R, Oechslin E, Schneider J, Attenhofer Jost C, Kaufmann PA. Echocardiographic and pathoanatomical characteristics of isolated left ventricular non-compaction: a step towards classification as a distinct cardiomyopathy. Heart. 2001;86:666–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Oechslin E, Jenni R. Left ventricular non-compaction revisited: a distinct phenotype with genetic heterogeneity? Eur Heart J. 2011;32:1446–56.

    Article  PubMed  Google Scholar 

  63. Punn R, Silverman NH. Cardiac segmental analysis in left ventricular noncompaction: experience in a pediatric population. J Am Soc Echocardiogr. 2010;23:46–53.

    Article  PubMed  Google Scholar 

  64. McMahon CJ, Pignatelli RH, Nagueh SF, et al. Left ventricular non-compaction cardiomyopathy in children: characterisation of clinical status using tissue Doppler-derived indices of left ventricular diastolic relaxation. Heart. 2007;93:676–81.

    Article  PubMed  Google Scholar 

  65. Eidem BW. Noninvasive evaluation of left ventricular noncompaction: what’s new in 2009? Pediatr Cardiol. 2009;30:682–9.

    Article  PubMed  Google Scholar 

  66. van Dalen BM, Caliskan K, Soliman OI, et al. Left ventricular solid body rotation in non-compaction cardiomyopathy: a potential new objective and quantitative functional diagnostic criterion? Eur J Heart Fail. 2008;10:1088–93.

    Article  PubMed  Google Scholar 

  67. Petersen SE, Selvanayagam JB, Wiesmann F, et al. Left ventricular non-compaction: insights from cardiovascular magnetic resonance imaging. J Am Coll Cardiol. 2005;46:101–5.

    Article  PubMed  Google Scholar 

  68. Thuny F, Jacquier A, Jop B, et al. Assessment of left ventricular non-compaction in adults: side-by-side comparison of cardiac magnetic resonance imaging with echocardiography. Arch Cardiovasc Dis. 2010;103:150–9.

    Article  PubMed  Google Scholar 

  69. Jacquier A, Thuny F, Jop B, et al. Measurement of trabeculated left ventricular mass using cardiac magnetic resonance imaging in the diagnosis of left ventricular non-compaction. Eur Heart J. 2010;31:1098–104.

    Article  PubMed  Google Scholar 

  70. Uribe S, Cadavid L, Hussain T, et al. Cardiovascular magnetic resonance findings in a pediatric population with isolated left ventricular non-compaction. J Cardiovasc Magn Reson. 2012;14:9.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Paterick TE, Tajik AJ. Left ventricular noncompaction a diagnostically challenging cardiomyopathy. Circ J. 2012;76:1556–62.

    Article  PubMed  Google Scholar 

  72. Melendez-Ramirez G, Castillo-Castellon F, Espinola-Zavaleta N, Meave A, Kimura-Hayama ET. Left ventricular noncompaction: a proposal of new diagnostic criteria by multidetector computed tomography. J Cardiovasc Comput Tomogr. 2012;6:346–54.

    Article  PubMed  Google Scholar 

  73. Hollingsworth CL, Yoshizumi TT, Frush DP, et al. Pediatric cardiac-gated CT angiography: assessment of radiation dose. Am J Roentgenol. 2007;189:12–8.

    Article  Google Scholar 

  74. Nihei K, Shinomiya N, Kabayama H, et al. Wolff-Parkinson-White (WPW) syndrome in isolated noncompaction of the ventricular myocardium (INVM). Circ J. 2004;68:82–4.

    Article  PubMed  Google Scholar 

  75. Caliskan K, Szili-Torok T, Theuns DA, et al. Indications and outcome of implantable cardioverter-defibrillators for primary and secondary prophylaxis in patients with noncompaction cardiomyopathy. J Cardiovasc Electrophysiol. 2011;22:898–904.

    Article  PubMed  Google Scholar 

  76. Kobza R, Steffel J, Erne P, et al. Implantable cardioverter-defibrillator and cardiac resynchronization therapy in patients with left ventricular noncompaction. Heart Rhythm. 2010;7:1545–9.

    Article  PubMed  Google Scholar 

  77. Van Malderen S, Wijchers S, Akca F, Caliskan K, Szili-Torok T. Mismatch between the origin of premature ventricular complexes and the noncompacted myocardium in patients with noncompaction cardiomyopathy patients: involvement of the conduction system? Ann Noninvasive Electrocardiol. 2016. https://doi.org/10.1111/anec.12394. [Epub ahead of print].

    Article  PubMed Central  Google Scholar 

  78. Jefferies JL, Wilkinson JD, Sleeper LA, et al. Cardiomyopathy phenotypes and outcomes for children with left ventricular myocardial noncompaction: Results from the Pediatric Cardiomyopathy Registry. J Card Fail. 2015;21(11):877–84.

    Article  PubMed  PubMed Central  Google Scholar 

  79. van Waning JI, Caliskan K, Hoedemaekers YM, et al. Genetics, clinical features, and long-term outcome of noncompaction cardiomyopathy. J Am Coll Cardiol. 2018;71(7):711–22.

    Article  PubMed  Google Scholar 

  80. Sasse-Klaassen S, Gerull B, Oechslin E, Jenni R, Thierfelder L. Isolated noncompaction of the left ventricular myocardium in the adult is an autosomal dominant disorder in the majority of patients. Am J Med Genet A. 2003;119A:162–7.

    Article  PubMed  Google Scholar 

  81. Digilio M, Bernardini L, Gagliardi M, et al. Syndromic non-compaction of the left ventricle: associated chromosomal anomalies. Clin Genet. 2013;84(4):362–7.

    Article  CAS  PubMed  Google Scholar 

  82. Beken S, Cevik A, Turan O, et al. A neonatal case of left ventricular noncompaction associated with trisomy 18. Genet Couns. 2011;22(2):161–4.

    CAS  PubMed  Google Scholar 

  83. Yukifumi M, Hirohiko S, Fukiko I, Mariko M. Trisomy 13 in a 9-year-old girl with left ventricular noncompaction. Pediatr Cardiol. 2011;32(2):206–7.

    Article  PubMed  Google Scholar 

  84. Blinder JJ, Martinez HR, Craigen WJ, Belmont J, Pignatelli RH, Jefferies JL. Noncompaction of the left ventricular myocardium in a boy with a novel chromosome 8p23.1 deletion. Am J Med Genet A. 2011;155A(9):2215–20.

    Article  PubMed  CAS  Google Scholar 

  85. Martinez HR, Niu MC, Sutton VR, et al. Coffin-Lowry syndrome and left ventricular noncompaction cardiomyopathy with a restrictive pattern. Am J Med Genet A. 2011;155A(12):3030–4.

    Article  PubMed  Google Scholar 

  86. Martinez HR, Belmont JW, Craigen WJ, Taylor MD, Jefferies JL. Left ventricular noncompaction in Sotos syndrome. Am J Med Genet A. 2011;155A(5):1115–8.

    Article  PubMed  Google Scholar 

  87. Zechner U, Kohlschmidt N, Kempf O, et al. Familial Sotos syndrome caused by a novel missense mutation, C2175S, in NSD1 and associated with normal intelligence, insulin dependent diabetes, bronchial asthma, and lipedema. Eur J Med Genet. 2009;52(5):306–10.

    Article  PubMed  Google Scholar 

  88. Sellars EA, Zimmerman SL, Smolarek T, Hopkin RJ. Ventricular noncompaction and absent thumbs in a newborn with tetrasomy 5q35.2-5q35.3: an association with Hunter-McAlpine syndrome? Am J Med Genet A. 2011;155A(6):1409–13.

    Article  PubMed  CAS  Google Scholar 

  89. Corrado G, Checcarelli N, Santarone M, Stollberger C, Finsterer J. Left ventricular hypertrabeculation/noncompaction with PMP22 duplication-based Charcot-Marie-Tooth disease type 1A. Cardiology. 2006;105(3):142–5.

    Article  PubMed  Google Scholar 

  90. Klaassen S, Probst S, Oechslin E, et al. Mutations in sarcomere protein genes in left ventricular noncompaction. Circulation. 2008;117:2893–901.

    Article  CAS  PubMed  Google Scholar 

  91. Hoedemaekers YM, Caliskan K, Michels M, et al. The importance of genetic counseling, DNA diagnostics, and cardiologic family screening in left ventricular noncompaction cardiomyopathy. Circ Cardiovasc Genet. 2010;3:232–9.

    Article  PubMed  Google Scholar 

  92. Miller EM, Hinton RB, Czosek R, Lorts A, Parrott A, Shikany AR, Ittenbach RF, Ware SM. Genetic testing in pediatric left ventricular noncompaction. Circ Cardiovasc Genet. 2017;10(6). pii: e001735. https://doi.org/10.1161/CIRCGENETICS.117.001735.

  93. Towbin JA, Jefferies JL. Cardiomyopathies Due to Left Ventricular Noncompaction, Mitochondrial and Storage Diseases, and Inborn Errors of Metabolism. Circ Res. 2017;21:838–54.

    Article  CAS  Google Scholar 

  94. Finsterer J, Stöllberger C, Towbin JA. Left ventricular noncompaction cardiomyopathy: cardiac, neuromuscular, and genetic factors. Nat Rev Cardiol. 2017;14:224–37.

    Article  PubMed  Google Scholar 

  95. Parent JJ, Towbin JA, Jefferies JL. Left ventricular noncompaction in a family with lamin A/C gene mutation. Tex Heart Inst J. 2015;42:73–6.

    Article  PubMed  PubMed Central  Google Scholar 

  96. Shan L, Makita N, Xing Y, et al. SCN5A variants in Japanese patients with left ventricular noncompaction and arrhythmia. Mol Genet Metab. 2008;93:468–74.

    Article  CAS  PubMed  Google Scholar 

  97. Towbin JA. Ion channel dysfunction associated with arrhythmia, ventricular noncompaction, and mitral valve prolapse a new overlapping phenotype. J Am Coll Cardiol. 2014;64(8):768–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Schweizer PA, Schröter J, Greiner S, Haas J, Yampolsky P, Mereles D, Buss SJ, Seyler C, Bruehl C, Draguhn A, Koenen M, Meder B, Katus HA, Thomas D. The symptom complex of familial sinus node dysfunction and myocardial noncompaction is associated with mutations in the HCN4 channel. J Am Coll Cardiol. 2014;64(8):757–67.

    Article  CAS  PubMed  Google Scholar 

  99. Milano A, Vermeer AM, Lodder EM, Barc J, Verkerk AO, Postma AV, van der Bilt IA, Baars MJ, van Haelst PL, Caliskan K, Hoedemaekers YM, Le Scouarnec S, Redon R, Pinto YM, Christiaans I, Wilde AA, Bezzina CR. HCN4 mutations in multiple families with bradycardia and left ventricular noncompaction cardiomyopathy. J Am Coll Cardiol. 2014;64(8):745–56.

    Article  CAS  PubMed  Google Scholar 

  100. Towbin JA, Lorts A, Jefferies JL. Left ventricular non-compaction cardiomyopathy. Lancet. 2015;386(9995):813–25.

    Article  PubMed  Google Scholar 

  101. Bleyl SB, Mumford BR, Brown-Harrison MC, et al. Xq28-linked noncompaction of the left ventricular myocardium: prenatal diagnosis and pathologic analysis of affected individuals. Am J Med Genet. 1997;72(3):257–65.

    Article  CAS  PubMed  Google Scholar 

  102. Ouyang P, Saarel E, Bai Y, et al. A de novo mutation in NKX2.5 associated with atrial septal defects, ventricular noncompaction, syncope and sudden death. Clin Chim Acta. 2011;412:170–5.

    Article  CAS  PubMed  Google Scholar 

  103. Postma AV, van Engelen K, van de Meerakker J, et al. Mutations in the sarcomere gene MYH7 in Ebstein anomaly. Circ Cardiovasc Genet. 2011;4:43–50.

    Article  CAS  PubMed  Google Scholar 

  104. Kelle AM, Bentley SJ, Rohena LO, Cabalka AK, Olson TM. Ebstein anomaly, left ventricular non-compaction, and early onset heart failure associated with a de novo α-tropomyosin gene mutation. Am J Med Genet A. 2016;170(8):2186–90.

    Article  CAS  PubMed  Google Scholar 

  105. Probst S, Oechslin E, Schuler P, et al. Sarcomere gene mutations in isolated left ventricular noncompaction cardiomyopathy do not predict clinical phenotype. Circ Cardiovasc Genet. 2011;4:367–74.

    Article  CAS  PubMed  Google Scholar 

  106. Dellefave LM, Pytel P, Mewborn S, et al. Sarcomere mutations in cardiomyopathy with left ventricular hypertrabeculation. Circ Cardiovasc Genet. 2009;2:442–9.

    Article  CAS  PubMed  Google Scholar 

  107. Hastings R, de Villiers CP, Hooper C, et al. Combination of whole genome sequencing, linkage, and functional studies implicates a missense mutation in titin as a cause of autosomal dominant cardiomyopathy with features of left ventricular noncompaction. Circ Cardiovasc Genet. 2016;9:426–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Bagnall RD, Molloy LK, Kalman JM, Semsarian C. Exome sequencing identifies a mutation in the ACTN2 gene in a family with idiopathic ventricular fibrillation, left ventricular noncompaction, and sudden death. BMC Med Genet. 2014;15:99.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  109. Finsterer J, Stollberger C. Primary myopathies and the heart. Scand Cardiovasc J. 2008;42:9–24.

    Article  PubMed  Google Scholar 

  110. Ramond F, Janin A, Di Filippo S, et al. Homozygous PKP2 deletion associated with neonatal left ventricle noncompaction. Clin Genet. 2017;91:126–30.

    Article  CAS  PubMed  Google Scholar 

  111. Tang S, Batra A, Zhang Y, Ebenroth ES, Huang T. Left ventricular noncompaction is associated with mutations in the mitochondrial genome. Mitochondrion. 2010;10:350–7.

    Article  CAS  PubMed  Google Scholar 

  112. Arndt AK, Schafer S, Drenckhahn JD, et al. Fine mapping of the 1p36 deletion syndrome identifies mutation of PRDM16 as a cause of cardiomyopathy. Am J Hum Genet. 2013;93:67–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Pearce FB, Litovsky SH, Dabal RJ, et al. Pathologic features of dilated cardiomyopathy with localized noncompaction in a child with deletion 1p36 syndrome. Congenit Heart Dis. 2012;7:59–61.

    Article  PubMed  Google Scholar 

  114. Teekakirikul P, Kelly MA, Rehm HL, Lakdawala NK, Funke BH. Inherited cardiomyopathies: molecular genetics and clinical genetic testing in the postgenomic era. J Mol Diagn. 2013;15:158–70.

    Article  PubMed  Google Scholar 

  115. Schreiber SL, Crabtree GR. Immunophilins, ligands, and the control of signal transduction. Harvey Lect. 1995;91:99–114.

    PubMed  Google Scholar 

  116. Wang T, Donahoe PK. The immunophilin FKBP12: a molecular guardian of the TGF-beta family type I receptors. Front Biosci. 2004;9:619–31.

    Article  CAS  PubMed  Google Scholar 

  117. Cameron AM, Steiner JP, Roskams AJ, Ali SM, Ronnett GV, Snyder SH. Calcineurin associated with the inositol 1,4,5-trisphosphate receptor-FKBP12 complex modulates Ca2+ flux. Cell. 1995;83:463–72.

    Article  CAS  PubMed  Google Scholar 

  118. Maruyama M, Li BY, Chen H, et al. FKBP12 is a critical regulator of the heart rhythm and the cardiac voltage-gated sodium current in mice. Circ Res. 2011;108:1042–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Shou W, Aghdasi B, Armstrong DL, et al. Cardiac defects and altered ryanodine receptor function in mice lacking FKBP12. Nature. 1998;391:489–92.

    Article  CAS  PubMed  Google Scholar 

  120. Chen H, Zhang W, Sun X, et al. Fkbp1a controls ventricular myocardium trabeculation and compaction by regulating endocardial Notch1 activity. Development. 2013;140:1946–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Luxan G, Casanova JC, Martinez-Poveda B, et al. Mutations in the NOTCH pathway regulator MIB1 cause left ventricular noncompaction cardiomyopathy. Nat Med. 2013;19:193–201.

    Article  CAS  PubMed  Google Scholar 

  122. Chen H, Shi S, Acosta L, et al. BMP10 is essential for maintaining cardiac growth during murine cardiogenesis. Development. 2004;131:2219–31.

    Article  CAS  PubMed  Google Scholar 

  123. Zhao C, Guo H, Li J, et al. Numb family proteins are essential for cardiac morphogenesis and progenitor differentiation. Development. 2014;141:281–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Pashmforoush M, Lu JT, Chen H, et al. Nkx2-5 pathways and congenital heart disease; loss of ventricular myocyte lineage specification leads to progressive cardiomyopathy and complete heart block. Cell. 2004;117:373–86.

    Article  CAS  PubMed  Google Scholar 

  125. Ashraf H, Pradhan L, Chang EI, et al. A mouse model of human congenital heart disease: high incidence of diverse cardiac anomalies and ventricular noncompaction produced by heterozygous Nkx2-5 homeodomain missense mutation. Circ Cardiovasc Genet. 2014;7:423–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Chen Q, Chen H, Zheng D, et al. Smad7 is required for the development and function of the heart. J Biol Chem. 2009;284:292–300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Liu J, Farmer JD Jr, Lane WS, Friedman J, Weissman I, Schreiber SL. Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes. Cell. 1991;66:807–15.

    Article  CAS  PubMed  Google Scholar 

  128. de la Pompa JL, Timmerman LA, Takimoto H, et al. Role of the NF-ATc transcription factor in morphogenesis of cardiac valves and septum. Nature. 1998;392:182–6.

    Article  PubMed  Google Scholar 

  129. Whetstine JR, Nottke A, Lan F, et al. Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases. Cell. 2006;125:467–81.

    Article  CAS  PubMed  Google Scholar 

  130. Shen X, Kim W, Fujiwara Y, et al. Jumonji modulates polycomb activity and self-renewal versus differentiation of stem cells. Cell. 2009;139:1303–14.

    Article  PubMed  PubMed Central  Google Scholar 

  131. Landeira D, Sauer S, Poot R, et al. Jarid2 is a PRC2 component in embryonic stem cells required for multi-lineage differentiation and recruitment of PRC1 and RNA Polymerase II to developmental regulators. Nat Cell Biol. 2010;12:618–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Mysliwiec MR, Bresnick EH, Lee Y. Endothelial Jarid2/Jumonji is required for normal cardiac development and proper Notch1 expression. J Biol Chem. 2011;286:17193–204.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Grego-Bessa J, Luna-Zurita L, del Monte G, et al. Notch signaling is essential for ventricular chamber development. Dev Cell. 2007;12:415–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Jefferies JL. Barth syndrome. Am J Med Genet C Semin Med Genet. 2013;163:198–205.

    Article  CAS  PubMed Central  Google Scholar 

  135. Phoon CK, Acehan D, Schlame M, et al. Tafazzin knockdown in mice leads to a developmental cardiomyopathy with early diastolic dysfunction preceding myocardial noncompaction. J Am Heart Assoc. 2012;1. pii: jah3-e000455. https://doi.org/10.1161/JAHA.111.000455.

  136. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;62:e147–239.

    Article  PubMed  Google Scholar 

  137. Gersh BJ, Maron BJ, Bonow RO, et al. American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2011;58:e212–60.

    Article  CAS  PubMed  Google Scholar 

  138. Pitta S, Thatai D, Afonso L. Thromboembolic complications of left ventricular noncompaction: case report and brief review of the literature. J Clin Ultrasound. 2007;35:465–8.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Heart Institute, Le Bonheur Children’s Hospital, Memphis, TN, USA

    Jeffrey A. Towbin, Kaitlin Ryan & Jason Goldberg

  2. Cardiomyopathy Program, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Jeffrey A. Towbin, Kaitlin Ryan & Jason Goldberg

  3. Division of Pediatric Cardiology, University of Tennessee Health Science Center, Memphis, TN, USA

    Jeffrey A. Towbin, Kaitlin Ryan & Jason Goldberg

Authors
  1. Jeffrey A. Towbin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kaitlin Ryan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jason Goldberg
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jeffrey A. Towbin .

Editor information

Editors and Affiliations

  1. Erasmus MC University Medical Center, Department of Cardiology, Rotterdam, The Netherlands

    Kadir Caliskan

  2. Erasmus MC University Medical Center, The Thoraxcenter, Rotterdam, The Netherlands

    Osama I. Soliman

  3. Erasmus MC University Medical Center, Department of Cardiology, Rotterdam, The Netherlands

    Folkert J. ten Cate

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Towbin, J.A., Ryan, K., Goldberg, J. (2019). Noncompaction Cardiomyopathy in Childhood. In: Caliskan, K., Soliman, O., ten Cate, F. (eds) Noncompaction Cardiomyopathy. Springer, Cham. https://doi.org/10.1007/978-3-030-17720-1_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-17720-1_7

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-17719-5

  • Online ISBN: 978-3-030-17720-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation