Details of Disease

General Information of Disease (ID: DIS1DV90)

• Disease Name: Visceral heterotaxy
• Synonyms: heterotaxy, visceral; situs ambiguous; situs ambiguus; heterotaxia syndrome; partial situs inversus; heterotaxia; lateralization defect; incomplete situs inversus; heterotaxy syndrome; visceral heterotaxy
• Definition: A rare, genetic disorder in which symptoms are generally secondary to the abnormal location of the organs within the thoracic, abdominal, or peritoneal cavities. Anatomic and functional problems can include cardiac defects, intestinal malrotation leading to volvulus, biliary atresia, and various defects of the central nervous system, urinary tract, and skeleton.
• Disease Hierarchy:
  DIS6SVEE: Syndromic disease
  DISYKSRF: Genetic disease
  DIS7LR56: Congenital heart malformation
  DIS1DV90: Visceral heterotaxy
• Disease Identifiers:
  MONDO ID: MONDO_0018677
  MESH ID: D059446
  UMLS CUI: C3178805
  MedGen ID: 465273
  Orphanet ID: 450

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 4 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ACVR2B	TTLFRKS	Limited	Biomarker	[1]
MMP21	TTYRF5E	Strong	Biomarker	[2]
NODAL	TTK2O1Q	Strong	Biomarker	[3]
TDGF1	TTN7HMG	Strong	Biomarker	[4]

This Disease Is Related to 11 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
CFAP52	OTSSXF56	Limited	Autosomal recessive	[5]
CRELD1	OTBSPZFP	moderate	Genetic Variation	[6]
LEFTY2	OT3RX4QF	moderate	Biomarker	[7]
CERS1	OT6EYRM3	Strong	Genetic Variation	[8]
CFAP53	OTI76XGK	Strong	Genetic Variation	[9]
CFC1	OT5DHGI8	Strong	Genetic Variation	[10]
DNAH11	OT6IYFVV	Strong	Genetic Variation	[11]
EVC2	OTY0M5SD	Strong	Biomarker	[12]
GDF1	OTZ1VRBH	Strong	Genetic Variation	[8]
KCNE1	OTZNQUW9	Strong	Genetic Variation	[13]
SHROOM3	OTQKC5X2	Strong	Genetic Variation	[14]

References

• [1] Left-right axis malformations associated with mutations in ACVR2B, the gene for human activin receptor type IIB.Am J Med Genet. 1999 Jan 1;82(1):70-6. doi: 10.1002/(sici)1096-8628(19990101)82:1<70::aid-ajmg14>3.0.co;2-y.
• [2] MMP21 is mutated in human heterotaxy and is required for normal left-right asymmetry in vertebrates.Nat Genet. 2015 Nov;47(11):1260-3. doi: 10.1038/ng.3376. Epub 2015 Oct 5.
• [3] Identification and functional characterization of NODAL rare variants in heterotaxy and isolated cardiovascular malformations. Hum Mol Genet. 2009 Mar 1;18(5):861-71. doi: 10.1093/hmg/ddn411. Epub 2008 Dec 8.
• [4] Loss-of-function mutations in the EGF-CFC gene CFC1 are associated with human left-right laterality defects. Nat Genet. 2000 Nov;26(3):365-9. doi: 10.1038/81695.
• [5] 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.
• [6] Missense mutations in CRELD1 are associated with cardiac atrioventricular septal defects. Am J Hum Genet. 2003 Apr;72(4):1047-52. doi: 10.1086/374319. Epub 2003 Mar 11.
• [7] Characterization and mutation analysis of human LEFTY A and LEFTY B, homologues of murine genes implicated in left-right axis development.Am J Hum Genet. 1999 Mar;64(3):712-21. doi: 10.1086/302289.
• [8] Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands. Nat Genet. 2017 Nov;49(11):1593-1601. doi: 10.1038/ng.3970. Epub 2017 Oct 9.
• [9] Roles of the cilium-associated gene CCDC11 in left-right patterning and in laterality disorders in humans. Int J Dev Biol. 2017;61(3-4-5):267-276. doi: 10.1387/ijdb.160442yc.
• [10] Duplication and deletion of CFC1 associated with heterotaxy syndrome.DNA Cell Biol. 2015 Feb;34(2):101-6. doi: 10.1089/dna.2014.2616. Epub 2014 Nov 25.
• [11] DNAH11 variants and its association with congenital heart disease and heterotaxy syndrome.Sci Rep. 2019 Apr 30;9(1):6683. doi: 10.1038/s41598-019-43109-6.
• [12] Ellis-van Creveld syndrome and congenital heart defects: presentation of an additional 32 cases.Pediatr Cardiol. 2011 Oct;32(7):977-82. doi: 10.1007/s00246-011-0006-9. Epub 2011 May 1.
• [13] Drug-induced QT-interval prolongation and recurrent torsade de pointes in a child with heterotaxy syndrome and KCNE1 D85N polymorphism.J Electrocardiol. 2012 Nov-Dec;45(6):770-3. doi: 10.1016/j.jelectrocard.2012.07.013. Epub 2012 Sep 20.
• [14] SHROOM3 is a novel candidate for heterotaxy identified by whole exome sequencing.Genome Biol. 2011 Sep 21;12(9):R91. doi: 10.1186/gb-2011-12-9-r91.