Skip to main content

Advertisement

SpringerLink
Log in

Left Ventricular Noncompaction Syndrome: Genetic Insights and Therapeutic Perspectives

  • Myocardial Disease (A Abbate and G Sinagra, Section Editors)
  • Published:
Current Cardiology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

To discuss the association of left ventricular hypertrabeculation/noncompaction (LVHT/LVNC/NCCM) with genetic disease and to outline the therapeutic options for non-symptomatic and symptomatic LVHT.

Recent Findings

A number of new mutated genes have been recently detected being associated with LVHT. There are indications that microtubules changing cell polarity, the transcription factor Nkx2-5, and NOTCH-1 signaling are involved in the pathogenesis of LVHT. There are also indications that the PKC signaling pathway, which is involved in the regulation of gap junction intercellular communication, is disturbed in LVHT.

Summary

LVHT is the same as LVNC and is associated with pathogenic variants in > 110 mtDNA or nDNA genes. LVHT has been also reported in > 15 chromosomal defects. However, a causal relation between any of these variants and LVHT has not been proven. There is no general agreement on the treatment of LVHT. According to expert opinions, LVHT patients require anticoagulation if they meet the criteria for anticoagulation or an ICD if they meet the appropriate criteria. Heart failure therapy is equal to patients with other causes of heart failure.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Finsterer J, Stöllberger C, Towbin JA. Left ventricular noncompaction cardiomyopathy: cardiac, neuromuscular, and genetic factors. Nat Rev Cardiol. 2017;14:224–37. Comprehensive review about the etiology, pathophysiology, diagnosis, and treatment of the phenomenon.

  2. Finsterer J. Cardiogenetics, neurogenetics, and pathogenetics of left ventricular hypertrabeculation/noncompaction. Pediatr Cardiol. 2009;30:659–81.

    PubMed  Google Scholar 

  3. 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.

    CAS  PubMed  Google Scholar 

  4. Oechslin E, Jenni R. Left Ventricular Noncompaction: From Physiologic Remodeling to Noncompaction Cardiomyopathy. J Am Coll Cardiol. 2018;71:723–6.

    PubMed  Google Scholar 

  5. Stöllberger C, Gerecke B, Finsterer J, Engberding R. Refinement of echocardiographic criteria for left ventricular noncompaction. Int J Cardiol. 2013;165:463–7.

    PubMed  Google Scholar 

  6. 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.

    PubMed  Google Scholar 

  7. Jacquier A, Thuny F, Jop B, Giorgi R, Cohen F, Gaubert JY, 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.

    PubMed  Google Scholar 

  8. Thakur V, Jaeggi ET, Nield LE. A unique foetal case of left ventricular non-compaction associated with arrhythmia, structural cardiac anomalies, and agenesis of the ductus venosus. Cardiol Young. 2016;26:368–70.

    PubMed  Google Scholar 

  9. Liu Y, Chen H, Shou W. Potential Common Pathogenic Pathways for the Left Ventricular Noncompaction Cardiomyopathy (LVNC). Pediatr Cardiol. 2018;39:1099–106.

    PubMed  PubMed Central  Google Scholar 

  10. Moorman AF, Christoffels VM. Cardiac chamber formation: development, genes, and evolution. Physiol Rev. 2003;83:1223–67.

    CAS  PubMed  Google Scholar 

  11. Grego-Bessa J, Luna-Zurita L, del Monte G, Bolós V, Melgar P, Arandilla A, et al. Notch signaling is essential for ventricular chamber development. Dev Cell. 2007;12:415–29.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Stankunas K, Hang CT, Tsun ZY, Chen H, Lee NV, Wu JI, et al. Endocardial Brg1 represses ADAMTS1 to maintain the microenvironment for myocardial morphogenesis. Dev Cell. 2008;14:298–311.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Lai D, Liu X, Forrai A, Wolstein O, Michalicek J, Ahmed I, et al. Neuregulin 1 sustains the gene regulatory network in both trabecular and nontrabecular myocardium. Circ Res. 2010;107:715–27.

    CAS  PubMed  Google Scholar 

  14. Luxán G, Casanova JC, Martínez-Poveda B, Prados B, D'Amato G, MacGrogan D, et al. Mutations in the NOTCH pathway regulator MIB1 cause left ventricular noncompaction cardiomyopathy. Nat Med. 2013;19:193–201.

    PubMed  Google Scholar 

  15. Bai X, Zhou Y, Ouyang N, Liu L, Huang X, Tian J, et al. A de novo Mutation in the MTUS1 Gene Decreases the Risk of Non-compaction of Ventricular Myocardium via the Rac1/Cdc42 Pathway. Front Pediatr. 2019;7:247. https://doi.org/10.3389/fped.2019.00247.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Choquet C, Nguyen THM, Sicard P, Buttigieg E, Tran TT, Kober F, et al. Deletion of Nkx2-5 in trabecular myocardium reveals the developmental origins of pathological heterogeneity associated with ventricular non-compaction cardiomyopathy. PLoS Genet. 2018;14, e1007502. https://doi.org/10.1371/journal.pgen.1007502. Provides insights into the mechanism by which the transcription factor Nkx2-5 causes hypertrabeculation in mice.

  17. Del Monte-Nieto G, Ramialison M, Adam AAS, Wu B, Aharonov A, D'Uva G, et al. Control of cardiac jelly dynamics by NOTCH1 and NRG1 defines the building plan for trabeculation. Nature. 2018;557:439–45. Provides insights into the myocardial development mediated by NOTCH1 signaling.

  18. Xie Y, Liu S, Hu S, Wei Y. Cardiomyopathy-Associated Gene 1-Sensitive PKC-Dependent Connexin 43 Expression and Phosphorylation in Left Ventricular Noncompaction Cardiomyopathy. Cell Physiol Biochem. 2017;44:828–42.

    PubMed  Google Scholar 

  19. van Waning JI, Moesker J, Heijsman D, Boersma E, Majoor-Krakauer D. Systematic Review of Genotype-Phenotype Correlations in Noncompaction Cardiomyopathy. J Am Heart Assoc. 2019;8(23):e012993. https://doi.org/10.1161/JAHA.119.012993.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Gati S, Papadakis M, Papamichael ND, Zaidi A, Sheikh N, Reed M, et al. Reversible de novo left ventricular trabeculations in pregnant women: implications for the diagnosis of left ventricular noncompaction in low-risk populations. Circulation. 2014;130:475–83.

    PubMed  Google Scholar 

  21. Gati S, Chandra N, Bennett RL, Reed M, Kervio G, Panoulas VF, et al. Increased left ventricular trabeculation in highly trained athletes: do we need more stringent criteria for the diagnosis of left ventricular non-compaction in athletes? Heart. 2013;99:401–8.

    CAS  PubMed  Google Scholar 

  22. Finsterer J, Stöllberger C, Fazio G. Neuromuscular disorders in left ventricular hypertrabeculation/noncompaction. Curr Pharm Des. 2010;16:2895–904.

    CAS  PubMed  Google Scholar 

  23. Finsterer J, Stöllberger C, Wegmann R, Janssen LA. Acquired left ventricular hypertrabeculation/noncompaction in myotonic dystrophy type 1. Int J Cardiol. 2009;137:310–3.

    CAS  PubMed  Google Scholar 

  24. Finsterer J, Stöllberger C, Schubert B. Acquired left ventricular noncompaction as a cardiac manifestation of neuromuscular disorders. Scand Cardiovasc J. 2008;42:25–30.

    PubMed  Google Scholar 

  25. Finsterer J, Stöllberger C, Gaismayer K, Janssen B. Acquired noncompaction in Duchenne muscular dystrophy. Int J Cardiol. 2006;106:420–1.

    PubMed  Google Scholar 

  26. Finsterer J, Stöllberger C, Schubert B. Acquired left ventricular hypertrabeculation/noncompaction in mitochondriopathy. Cardiology. 2004;102:228–30.

    PubMed  Google Scholar 

  27. Ciolli A, de Matteis G, Trambaiolo P, Castro A, Stingone A, Altamura G. Is Left Ventricular Noncompaction Only a Morphological Feature? A Case of Disappearance of Noncompaction after Surgical Correction of Aorto-Right Ventricular Fistula, Interventricular Septal Defect and Aortic Stenosis. J Cardiovasc Echogr. 2015;25:26–8.

    PubMed  PubMed Central  Google Scholar 

  28. Møller DV, Andersen PS, Hedley P, Ersbøll MK, Bundgaard H, Moolman-Smook J, et al. The role of sarcomere gene mutations in patients with idiopathic dilated cardiomyopathy. Eur J Hum Genet. 2009;17:1241–9.

    PubMed  PubMed Central  Google Scholar 

  29. Al Senaidi K, Joshi N, Al-Nabhani M, Al-Kasbi G, Al Farqani A, Al-Thihli K, et al. Phenotypic spectrum of ALPK3-related cardiomyopathy. Am J Med Genet A. 2019;179:1235–40.

    PubMed  Google Scholar 

  30. Miszalski-Jamka K, Jefferies JL, Mazur W, Głowacki J, Hu J, Lazar M, Gibbs RA, Liczko J, Kłyś J, Venner E, Muzny DM, Rycaj J, Białkowski J, Kluczewska E, Kalarus Z, Jhangiani S, Al-Khalidi H, Kukulski T, Lupski JR, Craigen WJ, Bainbridge MN. Novel Genetic Triggers and Genotype-Phenotype Correlations in Patients With Left Ventricular Noncompaction. Circ Cardiovasc Genet 2017;10(4). doi: 10.1161/CIRCGENETICS.117.001763.

  31. Tian T, Wang J, Wang H, Sun K, Wang Y, Jia L, et al. A low prevalence of sarcomeric gene variants in a Chinese cohort with left ventricular non-compaction. Heart Vessels. 2015;30:258–64.

    PubMed  Google Scholar 

  32. Finsterer J, Stöllberger C, Grassberger M, Gerger D. Noncompaction in mitochondrial myopathy: visible on microscopy but absent on macroscopic inspection. Cardiology. 2013;125:146–9.

    PubMed  Google Scholar 

  33. Grothoff M, Pachowsky M, Hoffmann J, Posch M, Klaassen S, Lehmkuhl L, et al. Value of cardiovascular MR in diagnosing left ventricular non-compaction cardiomyopathy and in discriminating between other cardiomyopathies. Eur Radiol. 2012;22:2699–709.

    PubMed  PubMed Central  Google Scholar 

  34. Boban M, Pesa V, Beck N, Manola S, Zulj M, Rotim A, et al. Supplementary Diagnostic Landmarks of Left Ventricular Non-Compaction on Magnetic Resonance Imaging. Yonsei Med J. 2018;59:63–71.

    PubMed  Google Scholar 

  35. Dreisbach JG, Mathur S, Houbois CP, Oechslin E, Ross H, Hanneman K, et al. Cardiovascular magnetic resonance based diagnosis of left ventricular non-compaction cardiomyopathy: impact of cine bSSFP strain analysis. J Cardiovasc Magn Reson. 2020;22(1):9. https://doi.org/10.1186/s12968-020-0599-3.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Stöllberger C, Blazek G, Gessner M, Bichler K, Wegner C, Finsterer J. Neuromuscular comorbidity, heart failure, and atrial fibrillation as prognostic factors in left ventricular hypertrabeculation/noncompaction. Herz. 2015;40:906–11.

    PubMed  Google Scholar 

  37. Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37:2129–200.

    PubMed  Google Scholar 

  38. Bavishi A, Lima K, Choudhury L. A New Diagnosis of Left Ventricular Non-Compaction in a Patient Presenting with Acute Heart Failure. J Radiol Case Rep. 2018;12:10–5.

    PubMed  PubMed Central  Google Scholar 

  39. Li J, Franke J, Pribe-Wolferts R, Meder B, Ehlermann P, Mereles D, et al. Effects of β-blocker therapy on electrocardiographic and echocardiographic characteristics of left ventricular noncompaction. Clin Res Cardiol. 2015;104:241–9.

    CAS  PubMed  Google Scholar 

  40. Kido K, Guglin M. Anticoagulation Therapy in Specific Cardiomyopathies: Isolated Left Ventricular Noncompaction and Peripartum Cardiomyopathy. J Cardiovasc Pharmacol Ther. 2019;24:31–6.

    CAS  PubMed  Google Scholar 

  41. Robinson AA, Trankle CR, Eubanks G, Schumann C, Thompson P, Wallace RL, et al. Off-label Use of Direct Oral Anticoagulants Compared With Warfarin for Left Ventricular Thrombi. JAMA Cardiol. 2020. https://doi.org/10.1001/jamacardio.2020.0652.

  42. Stöllberger C, Wegner C, Finsterer J. CHADS2- and CHA2DS2VASc scores and embolic risk in left ventricular hypertrabeculation/noncompaction. J Stroke Cerebrovasc Dis. 2013;22:709–12.

    PubMed  Google Scholar 

  43. Stöllberger C, Finsterer J. New oral anticoagulants for stroke prevention in left ventricular hypertrabeculation/noncompaction? Int J Cardiol. 2013;168:2910–1.

    PubMed  Google Scholar 

  44. Sakai Y, Sato Y, Matsuo S, Imai S, Kunimasa T, Matsumoto N, et al. Perforation of the right ventricular free wall by an ICD lead in a patient with isolated noncompaction of the ventricular myocardium. Int J Cardiol. 2007;117:e104–6.

    PubMed  Google Scholar 

  45. Gleva MJ, Wang Y, Curtis JP, Berul CI, Huddleston CB, Poole JE. Complications Associated With Implantable Cardioverter Defibrillators in Adults With Congenital Heart Disease or Left Ventricular Noncompaction Cardiomyopathy (From the NCDR® Implantable Cardioverter-Defibrillator Registry). Am J Cardiol. 2017;120:1891–8.

    PubMed  Google Scholar 

  46. Bertini M, Balla C, Pavasini R, Boriani G. Efficacy of cardiac resynchronization therapy in patients with isolated ventricular noncompaction with dilated cardiomyopathy: a systematic review of the literature. J Cardiovasc Med (Hagerstown). 2018;19:324–8.

    Google Scholar 

  47. Minamisawa M, Koyama J, Kozuka A, Miura T, Ebisawa S, Motoki H, et al. Regression of left ventricular hypertrabeculation is associated with improvement in systolic function and favorable prognosis in adult patients with non-ischemic cardiomyopathy. J Cardiol. 2016;68:431–8.

    PubMed  Google Scholar 

  48. Vinardell JM, Avila MD, Santana O. Isolated Left Ventricular Noncompaction Cardiomyopathy: A Transient Disease? Rev Cardiovasc Med. 2016;17:80–4.

    PubMed  Google Scholar 

  49. Stöllberger C, Keller H, Finsterer J. Disappearance of left ventricular hypertrabeculation/noncompaction after biventricular pacing in a patient with polyneuropathy. J Card Fail. 2007;13:211–4.

    PubMed  Google Scholar 

  50. Uribarri A, Rojas SV, Avsar M, Hanke JS, Napp LC, Berliner D, et al. First series of mechanical circulatory support in non-compaction cardiomyopathy: Is LVAD implantation a safe alternative? Int J Cardiol. 2015;197:128–32.

    PubMed  Google Scholar 

  51. Kornberger A, Stock UA, Risteski P, Beiras FA. Left ventricular non-compaction cardiomyopathy and left ventricular assist device: a word of caution. J Cardiothorac Surg. 2016;11:108. https://doi.org/10.1186/s13019-016-0503-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Epstein AE, Abraham WT, Bianco NR, Kern KB, Mirro M, Rao SV, et al. Wearable cardioverter-defibrillator use in patients perceived to be at high risk early post-myocardial infarction. J Am Coll Cardiol. 2013;62:2000–7.

    PubMed  Google Scholar 

  53. Musmar A, Hammami MB, Alzaraq S, Aboushaar R, Levine E. New Diagnosis of Non-compaction Cardiomyopathy in a 43-Year-Old Man Presenting with Syncope. Cureus. 2019;11:e5107. https://doi.org/10.7759/cureus.5107.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Stöllberger C, Finsterer J. Wearable cardioverter-defibrillator in a patient with left ventricular noncompaction/hypertrabeculation, coronary artery disease, and polyneuropathy. Ann Noninvasive Electrocardiol. 2015;20:79–81.

    PubMed  Google Scholar 

  55. Reuschel E, Baessler A, Stöllberger C, Finsterer J, Maier L, Fischer M, et al. Interdisciplinary management of left ventricular hypertrabeculation/noncompaction during pregnancy with a wearable defibrillator. Int J Cardiol. 2016;223:154–8.

    CAS  PubMed  Google Scholar 

  56. Howard TS, Valdes SO, Hope KD, Morris SA, Landstrom AP, Schneider AE, et al. Association of Wolff-Parkinson-White With Left Ventricular Noncompaction Cardiomyopathy in Children. J Card Fail. 2019;25(12):1004–8. https://doi.org/10.1016/j.cardfail.2019.09.014.

    Article  PubMed  Google Scholar 

  57. Cojan-Minzat BO, Boarescu PM, Cismaru G, Rosu R, Cionca C, Pop D, et al. Catheter ablation of a right posterior accessory pathway in a patient with left ventricular noncompaction: A case report. Medicine (Baltimore). 2019;98(5):e14267. https://doi.org/10.1097/MD.0000000000014267.

    Article  Google Scholar 

  58. Jahnke C, Paetsch I, Hindricks G, Richter S. Non-compaction cardiomyopathy and incessant supraventricular tachycardia: an unusual first presentation. Eur Heart J. 2017;38(34):2633–4. https://doi.org/10.1093/eurheartj/ehx360.

    Article  PubMed  Google Scholar 

  59. Muser D, Liang JJ, Witschey WR, Pathak RK, Castro S, Magnani S, et al. Ventricular arrhythmias associated with left ventricular noncompaction: Electrophysiologic characteristics, mapping, and ablation. Heart Rhythm. 2017;14(2):166–75. https://doi.org/10.1016/j.hrthm.2016.11.014.

    Article  PubMed  Google Scholar 

  60. Basu R, Hazra S, Shanks M, Paterson DI, Oudit GY. Novel mutation in exon 14 of the sarcomere gene MYH7 in familial left ventricular noncompaction with bicuspid aortic valve. Circ Heart Fail. 2014;7(6):1059–62. https://doi.org/10.1161/CIRCHEARTFAILURE.114.001666.

    Article  PubMed  Google Scholar 

  61. Altenberger J, Hasenauer G, Granitz M, Stöllberger C, Finsterer J. Disappearance of left ventricular hypertrabeculation/noncompaction and sudden death in a patient with Turner mosaic syndrome. Am J Cardiol. 2012 Jul 15;110(2):314–5. https://doi.org/10.1016/j.amjcard.2012.02.070.

    Article  PubMed  Google Scholar 

  62. Navarrete G, Pozo E, Díez-Villanueva P, Olivera MJ, Caballero P, Jiménez-Borreguero LJ, et al. Spongious Ischemic Myocardium: Dealing With Morphological Criteria of Noncompaction Cardiomyopathy. Circ Heart Fail. 2017;10(1):e003718. https://doi.org/10.1161/CIRCHEARTFAILURE.116.003718.

    Article  PubMed  Google Scholar 

  63. Gan C, Hu J, Luo S, An Q, Lin K. Surgical restoration of left ventricular diastolic function: possible treatment for noncompaction cardiomyopathy. J Card Surg. 2014;29(6):827–8. https://doi.org/10.1111/jocs.12339.

    Article  PubMed  Google Scholar 

  64. Al-Kindi SG, El-Amm C, Ginwalla M, Hoit BD, Park SJ, Oliveira GH. Heart transplant outcomes in patients with left ventricular non-compaction cardiomyopathy. J Heart Lung Transplant. 2015;34(6):761–5. https://doi.org/10.1016/j.healun.2014.11.005.

    Article  PubMed  Google Scholar 

  65. Van Der Starre P, Deuse T, Pritts C, Brun C, Vogel H, Oyer P. Late profound muscle weakness following heart transplantation due to Danon disease. Muscle Nerve. 2013;47(1):135–7. https://doi.org/10.1002/mus.23517.

    Article  Google Scholar 

  66. Cerar A, Zemljic G, Frljak S, Jaklic M, Poglajen G, Sever M, et al. Transendocardial CD34+ Cell Transplantation in Noncompaction Cardiomyopathy: First-in-Man Case Study. Cell Transplant. 2018;27(7):1027–30. https://doi.org/10.1177/0963689718779349.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Smith JGW, Owen T, Bhagwan JR, Mosqueira D, Scott E, Mannhardt I, et al. Isogenic Pairs of hiPSC-CMs with Hypertrophic Cardiomyopathy/LVNC-Associated ACTC1 E99K Mutation Unveil Differential Functional Deficits. Stem Cell Reports. 2018;11:1226–43.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Grigoratos C, Barison A, Ivanov A, et al. Meta-Analysis of the Prognostic Role of Late Gadolinium Enhancement and Global Systolic Impairment in Left Ventricular Noncompaction. JACC Cardiovasc Imaging. 2019;12:2141–51.

    PubMed  Google Scholar 

  69. Zhou H, Lin X, Fang L, et al. Prolonged QTc indicates the clinical severity and poor prognosis in patients with isolated left ventricular non-compaction. Int J Cardiovasc Imaging. 2017;33:2013–20.

    PubMed  Google Scholar 

  70. Takasaki A, Hirono K, Hata Y, Wang C, Takeda M, Yamashita JK, et al. Sarcomere gene variants act as a genetic trigger underlying the development of left ventricular noncompaction. Pediatr Res. 2018;84:733–42.

    PubMed  Google Scholar 

  71. Yilmaz S, Gokben S, Serdaroglu G, Eraslan C, Mancini GM, Tekin H, et al. The expanding phenotypic spectrum of ARFGEF2 gene mutation: Cardiomyopathy and movement disorder. Brain Dev. 2016;38:124–7.

    PubMed  Google Scholar 

  72. Hirono K, Saito K, Munkhsaikhan U, Xu F, Wang C, Lu L, et al. Familial Left Ventricular Non-Compaction Is Associated With a Rare p.V407I Variant in Bone Morphogenetic Protein 10. Circ J. 2019;83:1737–46.

    CAS  PubMed  Google Scholar 

  73. Lan NSR, Fietz M, Pachter N, Paul V, Playford D. A case of vascular Ehlers-Danlos Syndrome with a cardiomyopathy and multi-system involvement. Cardiovasc Pathol. 2018;35:48–51.

    PubMed  Google Scholar 

  74. Olgac A, Öztoprak Ü, Kasapkara ÇS, Kılıç M, Yüksel D, Derinkuyu EB, et al. A rare case of primary coenzyme Q10 deficiency due to COQ9 mutation. J Pediatr Endocrinol Metab. 2020;33:165–70.

    CAS  PubMed  Google Scholar 

  75. Bohrer T, Klein HG, Elert O. Left ventricular non-compaction associated with a genetic variant of the CYP2C9 gene. Heart Lung Circ. 2006;15:269–71.

    PubMed  Google Scholar 

  76. Fan P, Lu CX, Dong XQ, Zhu D, Yang KQ, Liu KQ, et al. A novel phenotype with splicing mutation identified in a Chinese family with desminopathy. Chin Med J (Engl). 2019;132:127–34.

    Google Scholar 

  77. Williams T, Machann W, Kühler L, Hamm H, Müller-Höcker J, Zimmer M, et al. Novel desmoplakin mutation: juvenile biventricular cardiomyopathy with left ventricular non-compaction and acantholytic palmoplantar keratoderma. Clin Res Cardiol. 2011;100:1087–93.

    PubMed  PubMed Central  Google Scholar 

  78. Ader F, De Groote P, Réant P, Rooryck-Thambo C, Dupin-Deguine D, Rambaud C, et al. FLNC pathogenic variants in patients with cardiomyopathies: Prevalence and genotype-phenotype correlations. Clin Genet. 2019;96:317–29.

    CAS  PubMed  Google Scholar 

  79. Amiya E, Morita H, Hatano M, Nitta D, Hosoya Y, Maki H, et al. Fukutin gene mutations that cause left ventricular noncompaction. Int J Cardiol. 2016;222:727–9.

    PubMed  Google Scholar 

  80. McMillan HJ, Schwartzentruber J, Smith A, Lee S, Chakraborty P, Bulman DE, et al. Compound heterozygous mutations in glycyl-tRNA synthetase are a proposed cause of systemic mitochondrial disease. BMC Med Genet. 2014;15:36. https://doi.org/10.1186/1471-2350-15-36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Ojala T, Nupponen I, Saloranta C, Sarkola T, Sekar P, Breilin A, et al. Fetal left ventricular noncompaction cardiomyopathy and fatal outcome due to complete deficiency of mitochondrial trifunctional protein. Eur J Pediatr. 2015;174:1689–92.

    CAS  PubMed  Google Scholar 

  82. Yokoyama R, Kinoshita K, Hata Y, Abe M, Matsuoka K, Hirono K, et al. A mutant HCN4 channel in a family with bradycardia, left bundle branch block, and left ventricular noncompaction. Heart Vessels. 2018;33:802–19.

    PubMed  Google Scholar 

  83. Codron P, Pautot V, Tassin A, Sternberg D, Letournel F, Richard P, et al. Abundant electrical myotonia and left ventricular noncompaction: Unusual features of Danon disease due to a novel mutation in LAMP2 gene. Rev Neurol (Paris). 2019;175:201–3.

    CAS  Google Scholar 

  84. Hachiya A, Motoki N, Akazawa Y, Matsuzaki S, Hirono K, Hata Y, et al. Left ventricular non-compaction revealed by aortic regurgitation due to Kawasaki disease in a boy with LDB3 mutation. Pediatr Int. 2016;58:797–800.

    CAS  PubMed  Google Scholar 

  85. Piccolo P, Attanasio S, Secco I, Sangermano R, Strisciuglio C, Limongelli G, et al. MIB2 variants altering NOTCH signalling result in left ventricle hypertrabeculation/non-compaction and are associated with Ménétrier-like gastropathy. Hum Mol Genet. 2017;26:33–43.

    CAS  PubMed  Google Scholar 

  86. Eldomery MK, Akdemir ZC, Vögtle FN, Charng WL, Mulica P, Rosenfeld JA, et al. MIPEP recessive variants cause a syndrome of left ventricular non-compaction, hypotonia, and infantile death. Genome Med. 2016;8:106.

    PubMed  PubMed Central  Google Scholar 

  87. Prada CE, Jefferies JL, Grenier MA, Huth CM, Page KI, Spicer RL, et al. Malonyl coenzyme A decarboxylase deficiency: early dietary restriction and time course of cardiomyopathy. Pediatrics. 2012;130:e456–60.

    PubMed  Google Scholar 

  88. García-García J, Fernández-García MA, Blanco-Arias P, Díaz-Maroto-Cicuendez MI, Salmerón-Martínez F, Hidalgo-Olivares VM, et al. Non-compaction cardiomyopathy and early respiratory failure in an adult symptomatic female carrier of centronuclear myopathy caused by a MTM1 mutation. Neuromuscul Disord. 2018;28:952–5.

    PubMed  Google Scholar 

  89. Hirono K, Hata Y, Ibuki K, Yoshimura N. Familial Ebstein's anomaly, left ventricular noncompaction, and ventricular septal defect associated with an MYH7 mutation. J Thorac Cardiovasc Surg. 2014;148:e223–6.

    PubMed  Google Scholar 

  90. Rea G, Homfray T, Till J, Roses-Noguer F, Buchan RJ, Wilkinson S, et al. Histiocytoid cardiomyopathy and microphthalmia with linear skin defects syndrome: phenotypes linked by truncating variants in NDUFB11. Cold Spring Harb Mol Case Stud. 2017;3:a001271. https://doi.org/10.1101/mcs.a001271.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Ouyang P, Saarel E, Bai Y, Luo C, Lv Q, Xu 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.

    CAS  PubMed  Google Scholar 

  92. Bainbridge MN, Davis EE, Choi WY, Dickson A, Martinez HR, Wang M, et al. Loss of Function Mutations in NNT Are Associated With Left Ventricular Noncompaction. Circ Cardiovasc Genet. 2015;8:544–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Brndiarova M, Antonyova M, Dedinska I, Havlicekova Z, Jesenak M. Nephronophthisis type I, left ventricular non-compaction cardiomyopathy and reduced cilia motility-atypical manifestations of one disease. J Nephrol. 2020;33:183–6.

    PubMed  Google Scholar 

  94. Rowland TJ, Graw SL, Sweet ME, Gigli M, Taylor MR, Mestroni L. Obscurin Variants in Patients With Left Ventricular Noncompaction. J Am Coll Cardiol. 2016;68:2237–8.

    PubMed  PubMed Central  Google Scholar 

  95. Lubrano R, Versacci P, Guido G, Bellelli E, Andreoli G, Elli M. Might there be an association between polycystic kidney disease and noncompaction of the ventricular myocardium? Nephrol Dial Transplant. 2009;24:3884–6.

    PubMed  Google Scholar 

  96. Ramond F, Janin A, Di Filippo S, Chanavat V, Chalabreysse L, Roux-Buisson N, et al. Homozygous PKP2 deletion associated with neonatal left ventricle noncompaction. Clin Genet. 2017;91:126–30.

    CAS  PubMed  Google Scholar 

  97. Villa CR, Ryan TD, Collins JJ, Taylor MD, Lucky AW, Jefferies JL. Left ventricular non-compaction cardiomyopathy associated with epidermolysis bullosa simplex with muscular dystrophy and PLEC1 mutation. Neuromuscul Disord. 2015;25:165–8.

    PubMed  Google Scholar 

  98. Abdullah S, Hawkins C, Wilson G, Yoon G, Mertens L, Carter MT, et al. Noncompaction cardiomyopathy in an infant with Walker-Warburg syndrome. Am J Med Genet A. 2017;173:3082–6.

    PubMed  Google Scholar 

  99. Delplancq G, Tarris G, Vitobello A, Nambot S, Sorlin A, Philippe C, et al. Cardiomyopathy due to PRDM16 mutation: First description of a fetal presentation, with possible modifier genes. Am J Med Genet C Semin Med Genet. 2020;184:129–35.

    CAS  PubMed  Google Scholar 

  100. Kayvanpour E, Sedaghat-Hamedani F, Gi WT, Tugrul OF, Amr A, Haas J, et al. Clinical and genetic insights into non-compaction: a meta-analysis and systematic review on 7598 individuals. Clin Res Cardiol. 2019;108:1297–308.

    PubMed  Google Scholar 

  101. Nozaki Y, Kato Y, Uike K, Yamamura K, Kikuchi M, Yasuda M, et al. Co-Phenotype of Left Ventricular Non-Compaction Cardiomyopathy and Atypical Catecholaminergic Polymorphic Ventricular Tachycardia in Association With R169Q, a Ryanodine Receptor Type 2 Missense Mutation. Circ J. 2020;84:226–34.

    PubMed  Google Scholar 

  102. Jain-Ghai S, Cameron JM, Al Maawali A, Blaser S, MacKay N, Robinson B, et al. Complex II deficiency--a case report and review of the literature. Am J Med Genet A. 2013;161A:285–94.

    PubMed  Google Scholar 

  103. Wenger TL, Chow P, Randle SC, Rosen A, Birgfeld C, Wrede J, et al. Novel findings of left ventricular non-compaction cardiomyopathy, microform cleft lip and poor vision in patient with SMC1A-associated Cornelia de Lange syndrome. Am J Med Genet A. 2017;173:414–20.

    CAS  PubMed  Google Scholar 

  104. Hirono K, Ichida F, Nishio N, Ogawa-Tominaga M, Fushimi T, Feichtinger RG, et al. Mitochondrial complex deficiency by novel compound heterozygous TMEM70 variants and correlation with developmental delay, undescended testicle, and left ventricular noncompaction in a Japanese patient: A case report. Clin Case Rep. 2019;7:553–7.

    PubMed  PubMed Central  Google Scholar 

  105. Fujino M, Tsuda E, Hirono K, Nakata M, Ichida F, Hata Y, et al. The TNNI3 Arg192His mutation in a 13-year-old girl with left ventricular noncompaction. J Cardiol Cases. 2018;18:33–6.

    PubMed  PubMed Central  Google Scholar 

  106. Hastings R, de Villiers CP, Hooper C, Ormondroyd L, Pagnamenta A, Lise S, 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.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Krankenanstalt Rudolfstiftung, Messerli Institute, Postfach 20, 1180, Vienna, Austria

    Josef Finsterer

  2. 2nd Medical Department with Cardiology and Intensive Care Medicine, Krankenanstalt Rudolfstiftung, Vienna, Austria

    Claudia Stöllberger

Authors
  1. Josef Finsterer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Claudia Stöllberger
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

JF: design, literature search, discussion, and first draft; CS: literature search, discussion, critical comments, and first draft.

Corresponding author

Correspondence to Josef Finsterer.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

The research has been given ethical approval.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Myocardial Disease

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Finsterer, J., Stöllberger, C. Left Ventricular Noncompaction Syndrome: Genetic Insights and Therapeutic Perspectives. Curr Cardiol Rep 22, 84 (2020). https://doi.org/10.1007/s11886-020-01339-5

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11886-020-01339-5

Keywords

Search

Navigation