Details of Disease

General Information of Disease (ID: DISJ4QEG)

• Disease Name: Left ventricular noncompaction
• Synonyms: left ventricular noncompaction (disease); LVNC; left ventricular non-compaction cardiomyopathy; left ventricular non-compaction syndrome; left ventricular hypertrabeculation; spongy myocardium; Lv non-compaction syndrome
• Definition: Left ventricular noncompaction (LVNC) is a rare cardiomyopathy characterized anatomically by prominent left ventricular trabeculae and deep intratrabecular recesses causing progressive systolic and diastolic dysfunction, conduction abnormalities, and occasionally thromboembolic events.
• Disease Hierarchy:
  DIS6SVEE: Syndromic disease
  DISYBB39: Intrinsic cardiomyopathy
  DISBA1TN: Familial cardiomyopathy
  DISQBA23: Congenital heart disease
  DISJ4QEG: Left ventricular noncompaction
• Disease Identifiers:
  MONDO ID: MONDO_0018901
  UMLS CUI: C1960469
  MedGen ID: 450531
  HPO ID: HP:0030682
  Orphanet ID: 54260

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 9 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
BMP10	TTTG6H1	Limited	Autosomal dominant	[1]
MYBPC3	TT9WOBN	Limited	Genetic Variation	[2]
MYH7	TTNIMDP	Limited	Genetic Variation	[2]
SCN5A	TTZOVE0	Disputed	Genetic Variation	[3]
MYH7	TTNIMDP	Supportive	Autosomal dominant	[4]
TNNT2	TTWAS18	Supportive	Autosomal dominant	[5]
NNT	TTKIH76	Strong	Genetic Variation	[6]
TNNT2	TTWAS18	Strong	GermlineCausalMutation	[5]
HCN4	TTQP04A	Definitive	Genetic Variation	[3]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC39A8	DTLPQGT	Strong	Biomarker	[7]

This Disease Is Related to 17 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
BMP10	OTA3QKKG	Limited	Autosomal dominant	[1]
DTNA	OTVBIRH2	Limited	Genetic Variation	[8]
LDB3	OTGQL1AM	Limited	Genetic Variation	[9]
MIB2	OTJCC3HS	Limited	SusceptibilityMutation	[10]
SYNE2	OTBUXGQ0	Limited	Autosomal dominant	[1]
MIB1	OT5C404P	Supportive	Autosomal dominant	[11]
MYH7	OT4Z9T8N	Supportive	Autosomal dominant	[4]
MYH7B	OTCB2IJB	Supportive	Autosomal dominant	[12]
PKP2	OTJOVF68	Supportive	Autosomal dominant	[13]
PRDM16	OT0BGA27	Supportive	Autosomal dominant	[14]
TNNT2	OT80NN7R	Supportive	Autosomal dominant	[5]
TPM1	OTD73X6R	Supportive	Autosomal dominant	[15]
ACTC1	OTJU04B1	Strong	Genetic Variation	[16]
LMNA	OT3SG7ZR	Strong	Genetic Variation	[17]
MIPEP	OTB2IHCT	Strong	CausalMutation	[18]
NONO	OTN36Q6U	Strong	Genetic Variation	[19]
PLEKHM2	OT4ZYV73	Strong	SusceptibilityMutation	[20]

References

• [1] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [2] Biallelic mutation in MYH7 and MYBPC3 leads to severe cardiomyopathy with left ventricular noncompaction phenotype.Hum Mutat. 2019 Aug;40(8):1101-1114. doi: 10.1002/humu.23757. Epub 2019 Apr 24.
• [3] A mutant HCN4 channel in a family with bradycardia, left bundle branch block, and left ventricular noncompaction.Heart Vessels. 2018 Jul;33(7):802-819. doi: 10.1007/s00380-018-1116-6. Epub 2018 Jan 18.
• [4] Novel mutation in exon 14 of the sarcomere gene MYH7 in familial left ventricular noncompaction with bicuspid aortic valve. Circ Heart Fail. 2014 Nov;7(6):1059-62. doi: 10.1161/CIRCHEARTFAILURE.114.001666.
• [5] Severe familial left ventricular non-compaction cardiomyopathy due to a novel troponin T (TNNT2) mutation. Cardiovasc Res. 2010 Jun 1;86(3):452-60. doi: 10.1093/cvr/cvq009. Epub 2010 Jan 18.
• [6] Loss of Function Mutations in NNT Are Associated With Left Ventricular Noncompaction.Circ Cardiovasc Genet. 2015 Aug;8(4):544-52. doi: 10.1161/CIRCGENETICS.115.001026. Epub 2015 May 29.
• [7] Zinc transporter Slc39a8 is essential for cardiac ventricular compaction.J Clin Invest. 2018 Feb 1;128(2):826-833. doi: 10.1172/JCI96993. Epub 2018 Jan 16.
• [8] Novel gene mutations in patients with left ventricular noncompaction or Barth syndrome.Circulation. 2001 Mar 6;103(9):1256-63. doi: 10.1161/01.cir.103.9.1256.
• [9] Loss of function of hNav1.5 by a ZASP1 mutation associated with intraventricular conduction disturbances in left ventricular noncompaction.Circ Arrhythm Electrophysiol. 2012 Oct;5(5):1017-26. doi: 10.1161/CIRCEP.111.969220. Epub 2012 Aug 28.
• [10] MIB2 variants altering NOTCH signalling result in left ventricle hypertrabeculation/non-compaction and are associated with Mntrier-like gastropathy.Hum Mol Genet. 2017 Jan 1;26(1):33-43. doi: 10.1093/hmg/ddw365.
• [11] Mutations in the NOTCH pathway regulator MIB1 cause left ventricular noncompaction cardiomyopathy. Nat Med. 2013 Feb;19(2):193-201. doi: 10.1038/nm.3046. Epub 2013 Jan 13.
• [12] Digenic mutational inheritance of the integrin alpha 7 and the myosin heavy chain 7B genes causes congenital myopathy with left ventricular non-compact cardiomyopathy. Orphanet J Rare Dis. 2013 Jun 21;8:91. doi: 10.1186/1750-1172-8-91.
• [13] Homozygous PKP2 deletion associated with neonatal left ventricle noncompaction. Clin Genet. 2017 Jan;91(1):126-130. doi: 10.1111/cge.12780. Epub 2016 Apr 26.
• [14] Fine mapping of the 1p36 deletion syndrome identifies mutation of PRDM16 as a cause of cardiomyopathy. Am J Hum Genet. 2013 Jul 11;93(1):67-77. doi: 10.1016/j.ajhg.2013.05.015. Epub 2013 Jun 13.
• [15] Sarcomere gene mutations in isolated left ventricular noncompaction cardiomyopathy do not predict clinical phenotype. Circ Cardiovasc Genet. 2011 Aug 1;4(4):367-74. doi: 10.1161/CIRCGENETICS.110.959270. Epub 2011 May 6.
• [16] Familial left ventricular noncompaction associated with a novel mutation in the alpha-cardiac actin gene.Rev Esp Cardiol (Engl Ed). 2014 Oct;67(10):857-9. doi: 10.1016/j.rec.2014.05.015. Epub 2014 Sep 5.
• [17] Familial dilated cardiomyopathy and isolated left ventricular noncompaction associated with lamin A/C gene mutations.Am J Cardiol. 2004 Jul 1;94(1):50-4. doi: 10.1016/j.amjcard.2004.03.029.
• [18] MIPEP recessive variants cause a syndrome of left ventricular non-compaction, hypotonia, and infantile death. Genome Med. 2016 Nov 1;8(1):106. doi: 10.1186/s13073-016-0360-6.
• [19] Expanding the genetic and clinical spectrum of the NONO-associated X-linked intellectual disability syndrome.Am J Med Genet A. 2019 May;179(5):792-796. doi: 10.1002/ajmg.a.61091. Epub 2019 Feb 17.
• [20] PLEKHM2 mutation leads to abnormal localization of lysosomes, impaired autophagy flux and associates with recessive dilated cardiomyopathy and left ventricular noncompaction.Hum Mol Genet. 2015 Dec 20;24(25):7227-40. doi: 10.1093/hmg/ddv423. Epub 2015 Oct 12.