Details of Disease

Disease Name

Congenital diaphragmatic hernia

unilateral agenesis of diaphragm; congenital diaphragmatic defect; agenesis of hemidiaphragm; diaphragmatic hernia; congenital diaphragmatic hernia; CDH

Definition

A posterolateral defect of the diaphragm that allows passage of abdominal viscera into the thorax, leading to respiratory insufficiency and persistent pulmonary hypertension with high mortality.

Disease Hierarchy

DISU0K94: Hereditary skeletal muscle disorder

DISIOU8M: Diaphragm disorder

DIS0IPVU: Congenital diaphragmatic hernia

Disease Identifiers

MONDO ID

MONDO_0005711

MESH ID

D065630

UMLS CUI

C0235833

OMIM ID

142340

MedGen ID

68625

HPO ID

HP:0000776

Orphanet ID

2140

SNOMED CT ID

17190001

General Information of Disease (ID: DIS0IPVU)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 25 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CCN2	TTIL516	Limited	Biomarker	[1]
FOXC2	TTLBAP1	Limited	Biomarker	[2]
GATA4	TT1VDN2	Limited	Biomarker	[3]
IGF1R	TTQFBMY	Limited	Biomarker	[4]
IGF2R	TTPNE41	Limited	Biomarker	[4]
INSR	TTCBFJO	Limited	Biomarker	[4]
LHCGR	TT2O4W9	Limited	Biomarker	[5]
PIM1	TTTN5QW	Limited	Biomarker	[6]
RHOA	TTP2U16	Limited	Biomarker	[7]
WT1	TTZ8UT4	Limited	Biomarker	[8]
LRP2	TTPH1AJ	moderate	Genetic Variation	[9]
ABL1	TT6B75U	Strong	CausalMutation	[10]
CCL2	TTNAY0P	Strong	Biomarker	[11]
CYP2E1	TTWVHQ5	Strong	Genetic Variation	[12]
EDNRB	TT3ZTGU	Strong	Altered Expression	[13]
EPO	TTQG4NR	Strong	Biomarker	[14]
FGF10	TTNPEFX	Strong	Altered Expression	[15]
GDF5	TT37XV9	Strong	Biomarker	[16]
GPC3	TTJTSX4	Strong	Genetic Variation	[17]
ITGA8	TT1FW8B	Strong	Biomarker	[18]
KCNQ4	TT8HGRW	Strong	Altered Expression	[19]
KCNQ5	TTWVL5Q	Strong	Altered Expression	[19]
RARB	TTISP28	Strong	Genetic Variation	[20]
RGMA	TTURJV4	Strong	Genetic Variation	[21]
STAT3	TTHJT3X	Strong	Biomarker	[22]
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⏷ Show the Full List of 25 DTT(s)

This Disease Is Related to 3 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
ALDH1A2	DEKN1H4	Strong	Altered Expression	[23]
CHDH	DEAHED0	Strong	Biomarker	[24]
EGLN3	DEMQTKH	Strong	Altered Expression	[25]
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This Disease Is Related to 48 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
DES	OTI09KBW	Limited	Biomarker	[26]
DISP1	OTLDFZSY	Limited	Altered Expression	[27]
FOXF1	OT2CJZ5K	Limited	Biomarker	[2]
GATA6	OTO2BC0F	Limited	Genetic Variation	[28]
HLX	OT7DTH46	Limited	Biomarker	[29]
MEF2A	OTV2SF6E	Limited	Genetic Variation	[30]
MYOD1	OTV2S79X	Limited	Biomarker	[31]
RPS19	OTBKGP48	Limited	Genetic Variation	[32]
SFTPB	OTOHS07E	Limited	Biomarker	[33]
SFTPC	OTIZJD09	Limited	Altered Expression	[34]
SIN3A	OTM8OZWV	Limited	Autosomal dominant	[35]
SLIT3	OTU8MKEU	Limited	Biomarker	[36]
AQP6	OTXS6UYY	Strong	Biomarker	[37]
ARRDC4	OTINJ0FX	Strong	Genetic Variation	[21]
ASAH2	OT47TIF3	Strong	Biomarker	[38]
CD79A	OTOJC8DV	Strong	Biomarker	[39]
CDH15	OTJ1TO02	Strong	Biomarker	[40]
CHD2	OTRKL6YC	Strong	Biomarker	[41]
CHMP2B	OTZA7RJB	Strong	Biomarker	[42]
CRISPLD2	OTVSFHTL	Strong	Altered Expression	[43]
DMRT1	OT5PU9U1	Strong	Biomarker	[42]
DSEL	OTVNQD3I	Strong	Biomarker	[44]
EMILIN1	OT94R6M1	Strong	Altered Expression	[45]
FBN1	OTYCJT63	Strong	Altered Expression	[46]
FGFRL1	OT8HZ3ZL	Strong	Biomarker	[47]
FRAS1	OTLPESF3	Strong	Genetic Variation	[48]
FREM1	OTMHRV87	Strong	Genetic Variation	[48]
FREM2	OTEK6BZR	Strong	Biomarker	[48]
FZD2	OT952ML1	Strong	Genetic Variation	[49]
LLGL1	OTAIQSXZ	Strong	Altered Expression	[43]
MYL2	OT78PC0C	Strong	Biomarker	[50]
MYRF	OTKF6AEB	Strong	Genetic Variation	[51]
NDST1	OT9E10W2	Strong	Altered Expression	[52]
NEIL2	OTV6JEON	Strong	Biomarker	[53]
NIPBL	OTF6OOLU	Strong	Genetic Variation	[54]
NOSIP	OTQTNFPJ	Strong	Altered Expression	[55]
NR2F1	OTGWZWYL	Strong	Genetic Variation	[56]
NR2F2	OTJFS67N	Strong	Genetic Variation	[30]
PIGN	OTHHTJKX	Strong	Genetic Variation	[57]
PIGW	OTT9SMTF	Strong	Biomarker	[58]
PJA1	OTFKTMEI	Strong	Biomarker	[59]
RAD21	OTQS84ZF	Strong	Genetic Variation	[60]
SDHA	OTOJ8QFF	Strong	Altered Expression	[43]
SFTPA2	OT6SFOMU	Strong	Altered Expression	[61]
SOX7	OTOZOFAG	Strong	Genetic Variation	[62]
STARD8	OTY9IAKW	Strong	Biomarker	[59]
TBX2	OTTOT7A9	Strong	Altered Expression	[63]
TBX4	OTW58FG4	Strong	Altered Expression	[63]
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⏷ Show the Full List of 48 DOT(s)

References

1	Prenatal administration of retinoic acid upregulates connective tissue growth factor in the nitrofen CDH model.Pediatr Surg Int. 2011 Jun;27(6):573-7. doi: 10.1007/s00383-010-2833-9.
2	Downregulation of Forkhead box F1 gene expression in the pulmonary vasculature of nitrofen-induced congenital diaphragmatic hernia.Pediatr Surg Int. 2016 Dec;32(12):1121-1126. doi: 10.1007/s00383-016-3967-1. Epub 2016 Sep 23.
3	Decreased expression of GATA4 in the diaphragm of nitrofen-induced congenital diaphragmatic hernia.Birth Defects Res B Dev Reprod Toxicol. 2013 Apr;98(2):139-43. doi: 10.1002/bdrb.21037. Epub 2013 Feb 19.
4	Prenatal administration of retinoic acid upregulates insulin-like growth factor receptors in the nitrofen-induced hypoplastic lung.Birth Defects Res B Dev Reprod Toxicol. 2011 Apr;92(2):148-51. doi: 10.1002/bdrb.20293. Epub 2011 Mar 23.
5	Variability in antenatal prognostication of fetal diaphragmatic hernia across the North American Fetal Therapy Network (NAFTNet).Prenat Diagn. 2020 Feb;40(3):342-350. doi: 10.1002/pd.5560. Epub 2019 Dec 8.
6	Increased expression of activated pSTAT3 and PIM-1 in the pulmonary vasculature of experimental congenital diaphragmatic hernia.J Pediatr Surg. 2015 Jun;50(6):908-11. doi: 10.1016/j.jpedsurg.2015.03.007. Epub 2015 Mar 14.
7	Increased pulmonary RhoA expression in the nitrofen-induced congenital diaphragmatic hernia rat model.J Pediatr Surg. 2015 Sep;50(9):1467-71. doi: 10.1016/j.jpedsurg.2015.02.063. Epub 2015 Mar 7.
8	Expression of the Wilm's tumor gene WT1 during diaphragmatic development in the nitrofen model for congenital diaphragmatic hernia.Pediatr Surg Int. 2011 Feb;27(2):159-63. doi: 10.1007/s00383-010-2795-y.
9	Broadening the phenotype of LRP2 mutations: a new mutation in LRP2 causes a predominantly ocular phenotype suggestive of Stickler syndrome. Clin Genet. 2014 Sep;86(3):282-6. doi: 10.1111/cge.12265. Epub 2013 Sep 23.
10	Germline mutations in ABL1 cause an autosomal dominant syndrome characterized by congenital heart defects and skeletal malformations. Nat Genet. 2017 Apr;49(4):613-617. doi: 10.1038/ng.3815. Epub 2017 Mar 13.
11	Prenatal treatment with rosiglitazone attenuates vascular remodeling and pulmonary monocyte influx in experimental congenital diaphragmatic hernia.PLoS One. 2018 Nov 12;13(11):e0206975. doi: 10.1371/journal.pone.0206975. eCollection 2018.
12	Genetic polymorphisms of CYP2E1 and GSTM1 loci and susceptibility to anti-tuberculosis drug-induced hepatotoxicity.Int J Tuberc Lung Dis. 2014 May;18(5):588-93. doi: 10.5588/ijtld.13.0344.
13	Perturbations in Endothelial Dysfunction-Associated Pathways in the Nitrofen-Induced Congenital Diaphragmatic Hernia Model.J Vasc Res. 2018;55(1):26-34. doi: 10.1159/000484087. Epub 2017 Dec 8.
14	Suppressed erythropoietin expression in a nitrofen-induced congenital diaphragmatic hernia.Pediatr Pulmonol. 2017 May;52(5):606-615. doi: 10.1002/ppul.23640. Epub 2016 Nov 23.
15	Congenital diaphragmatic hernia as a potential target for transamniotic stem cell therapy.J Pediatr Surg. 2020 Feb;55(2):249-252. doi: 10.1016/j.jpedsurg.2019.10.033. Epub 2019 Nov 9.
16	Evidence of association between GDF5 polymorphisms and congenital dislocation of the hip in a Caucasian population.Osteoarthritis Cartilage. 2010 Sep;18(9):1144-9. doi: 10.1016/j.joca.2010.05.018. Epub 2010 Jul 13.
17	Whole exome sequencing and array-based molecular karyotyping as aids to prenatal diagnosis in fetuses with suspected Simpson-Golabi-Behmel syndrome.Prenat Diagn. 2016 Oct;36(10):961-965. doi: 10.1002/pd.4920. Epub 2016 Sep 27.
18	Decreased Expression of Integrin Subunits 3, 6, and 8 in the Branching Airway Mesenchyme of Nitrofen-Induced Hypoplastic Lungs.Eur J Pediatr Surg. 2018 Feb;28(1):109-114. doi: 10.1055/s-0037-1604022. Epub 2017 Jul 12.
19	Downregulation of KCNQ5 expression in the rat pulmonary vasculature of nitrofen-induced congenital diaphragmatic hernia.J Pediatr Surg. 2017 May;52(5):702-705. doi: 10.1016/j.jpedsurg.2017.01.016. Epub 2017 Jan 26.
20	Gain-of-Function Mutations in RARB Cause Intellectual Disability with Progressive Motor Impairment. Hum Mutat. 2016 Aug;37(8):786-93. doi: 10.1002/humu.23004. Epub 2016 May 9.
21	Array comparative genomic hybridization in patients with congenital diaphragmatic hernia: mapping of four CDH-critical regions and sequencing of candidate genes at 15q26.1-15q26.2.Eur J Hum Genet. 2006 Sep;14(9):999-1008. doi: 10.1038/sj.ejhg.5201652. Epub 2006 May 31.
22	STATs in Lung Development: Distinct Early and Late Expression, Growth Modulation and Signaling Dysregulation in Congenital Diaphragmatic Hernia.Cell Physiol Biochem. 2018;45(1):1-14. doi: 10.1159/000486218. Epub 2017 Dec 22.
23	Metabolic disturbances of the vitamin A pathway in human diaphragmatic hernia.Am J Physiol Lung Cell Mol Physiol. 2015 Jan 15;308(2):L147-57. doi: 10.1152/ajplung.00108.2014.
24	Preoperative cardiopulmonary evaluation in specific neonatal surgery.Semin Pediatr Surg. 2019 Feb;28(1):3-10. doi: 10.1053/j.sempedsurg.2019.01.002. Epub 2019 Jan 18.
25	Expression of hypoxia-inducible factors, regulators, and target genes in congenital diaphragmatic hernia patients.Pediatr Dev Pathol. 2011 Sep-Oct;14(5):384-90. doi: 10.2350/09-09-0705-OA.1. Epub 2011 Jun 14.
26	Decreased Desmin expression in the developing diaphragm of the nitrofen-induced congenital diaphragmatic hernia rat model.Pediatr Surg Int. 2016 Dec;32(12):1127-1132. doi: 10.1007/s00383-016-3968-0. Epub 2016 Sep 20.
27	Expression of dispatched RND transporter family member 1 is decreased in the diaphragmatic and pulmonary mesenchyme of nitrofen-induced congenital diaphragmatic hernia.Pediatr Surg Int. 2019 Jan;35(1):35-40. doi: 10.1007/s00383-018-4374-6. Epub 2018 Oct 31.
28	A novel GATA6 variant in a boy with neonatal diabetes and diaphragmatic hernia: a familial case with a review of the literature.J Pediatr Endocrinol Metab. 2019 Sep 25;32(9):1027-1030. doi: 10.1515/jpem-2019-0057.
29	HLX is a candidate gene for a pattern of anomalies associated with congenital diaphragmatic hernia, short bowel, and asplenia.Am J Med Genet A. 2017 Nov;173(11):3070-3074. doi: 10.1002/ajmg.a.38354. Epub 2017 Sep 12.
30	Germline but not somatic de novo mutations are common in human congenital diaphragmatic hernia.Birth Defects Res. 2018 Apr 17;110(7):610-617. doi: 10.1002/bdr2.1223. Epub 2018 Mar 23.
31	The role of primary myogenic regulatory factors in the developing diaphragmatic muscle in the nitrofen-induced diaphragmatic hernia.Pediatr Surg Int. 2011 Jun;27(6):579-82. doi: 10.1007/s00383-010-2834-8.
32	Bochdalek hernia with Diamond-Blackfan anemia associated with RPS19 gene mutation: A case report.Medicine (Baltimore). 2019 Sep;98(39):e17337. doi: 10.1097/MD.0000000000017337.
33	Protective effect of baicalin on fetal lung development in a rabbit model of congenital diaphragmatic hernia.Exp Ther Med. 2018 Jan;15(1):61-66. doi: 10.3892/etm.2017.5409. Epub 2017 Oct 31.
34	Follistatin-like 1 expression is decreased in the alveolar epithelium of hypoplastic rat lungs with nitrofen-induced congenital diaphragmatic hernia.J Pediatr Surg. 2017 May;52(5):706-709. doi: 10.1016/j.jpedsurg.2017.01.020. Epub 2017 Jan 28.
35	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.
36	Echocardiography allows for analysis of pulmonary arterial flow in mice with congenital diaphragmatic hernia.J Surg Res. 2018 Jan;221:35-42. doi: 10.1016/j.jss.2017.06.080.
37	Neonatal surgery in low- vs. high-volume institutions: a KID inpatient database outcomes and cost study after repair of congenital diaphragmatic hernia, esophageal atresia, and gastroschisis.Pediatr Surg Int. 2019 Nov;35(11):1293-1300. doi: 10.1007/s00383-019-04525-x. Epub 2019 Aug 1.
38	AAV2/8-humanFOXP3 gene therapy shows robust anti-atherosclerosis efficacy in LDLR-KO mice on high cholesterol diet.J Transl Med. 2015 Jul 18;13:235. doi: 10.1186/s12967-015-0597-7.
39	Genomic alterations in a case of alpha heavy chain disease leading to the generation of composite exons from the JH region.Eur J Immunol. 1989 Nov;19(11):2093-8. doi: 10.1002/eji.1830191119.
40	Ventricular Performance is Associated with Need for Extracorporeal Membrane Oxygenation in Newborns with Congenital Diaphragmatic Hernia.J Pediatr. 2017 Dec;191:28-34.e1. doi: 10.1016/j.jpeds.2017.08.060. Epub 2017 Oct 13.
41	Congenital diaphragmatic hernia and chromosome 15q26: determination of a candidate region by use of fluorescent in situ hybridization and array-based comparative genomic hybridization.Am J Hum Genet. 2005 May;76(5):877-82. doi: 10.1086/429842. Epub 2005 Mar 4.
42	Role of catalytic iron and oxidative stress in nitrofen-induced congenital diaphragmatic hernia and its amelioration by Saireito (TJ-114).J Clin Biochem Nutr. 2017 Nov;61(3):176-182. doi: 10.3164/jcbn.17-17. Epub 2017 Sep 5.
43	The effects of tracheal occlusion on Wnt signaling in a rabbit model of congenital diaphragmatic hernia.J Pediatr Surg. 2019 May;54(5):937-944. doi: 10.1016/j.jpedsurg.2019.01.024. Epub 2019 Jan 31.
44	A maternally inherited chromosome 18q22.1 deletion in a male with late-presenting diaphragmatic hernia and microphthalmia-evaluation of DSEL as a candidate gene for the diaphragmatic defect.Am J Med Genet A. 2010 Apr;152A(4):916-23. doi: 10.1002/ajmg.a.33341.
45	Downregulated Elastin Microfibril Interfacer 1 Expression in the Pulmonary Vasculature of Experimental Congenital Diaphragmatic Hernia.Eur J Pediatr Surg. 2018 Feb;28(1):115-119. doi: 10.1055/s-0037-1604026. Epub 2017 Jul 12.
46	Fibrillin-1 Expression Is Decreased in the Diaphragmatic Muscle Connective Tissue of Nitrofen-Induced Congenital Diaphragmatic Hernia.Eur J Pediatr Surg. 2017 Feb;27(1):26-31. doi: 10.1055/s-0036-1587586. Epub 2016 Aug 14.
47	Downregulation of FGFRL1 contributes to the development of the diaphragmatic defect in the nitrofen model of congenital diaphragmatic hernia.Eur J Pediatr Surg. 2011 Jan;21(1):46-9. doi: 10.1055/s-0030-1262853. Epub 2010 Oct 11.
48	The role of FREM2 and FRAS1 in the development of congenital diaphragmatic hernia.Hum Mol Genet. 2018 Jun 15;27(12):2064-2075. doi: 10.1093/hmg/ddy110.
49	Genomic alterations that contribute to the development of isolated and non-isolated congenital diaphragmatic hernia.J Med Genet. 2011 May;48(5):299-307. doi: 10.1136/jmg.2011.089680.
50	Embryonic essential myosin light chain regulates fetal lung development in rats.Am J Respir Cell Mol Biol. 2007 Sep;37(3):330-8. doi: 10.1165/rcmb.2006-0349OC. Epub 2007 May 31.
51	De novo variants in congenital diaphragmatic hernia identify MYRF as a new syndrome and reveal genetic overlaps with other developmental disorders.PLoS Genet. 2018 Dec 10;14(12):e1007822. doi: 10.1371/journal.pgen.1007822. eCollection 2018 Dec.
52	Down-regulation of N-deacetylase-N-sulfotransferase-1 signaling in the developing diaphragmatic vasculature of nitrofen-induced congenital diaphragmatic hernia.J Pediatr Surg. 2017 Jun;52(6):1035-1039. doi: 10.1016/j.jpedsurg.2017.03.036. Epub 2017 Mar 18.
53	Prenatal diagnosis of two fetuses with deletions of 8p23.1, critical region for congenital diaphragmatic hernia and heart defects.Am J Med Genet A. 2013 Jul;161A(7):1755-8. doi: 10.1002/ajmg.a.35965. Epub 2013 May 21.
54	Brachmann-de Lange syndrome with congenital diaphragmatic hernia and NIPBL gene mutation.Congenit Anom (Kyoto). 2010 Jun;50(2):129-32. doi: 10.1111/j.1741-4520.2010.00270.x. Epub 2010 Feb 11.
55	Expression of Nitric Oxide Synthase Interacting Protein (NOSIP) is Decreased in the Pulmonary Vasculature of Nitrofen-Induced Congenital Diaphragmatic Hernia.Eur J Pediatr Surg. 2019 Feb;29(1):102-107. doi: 10.1055/s-0038-1675772. Epub 2018 Dec 10.
56	COUP-TF Genes, Human Diseases, and the Development of the Central Nervous System in Murine Models.Curr Top Dev Biol. 2017;125:275-301. doi: 10.1016/bs.ctdb.2016.12.002. Epub 2017 Jan 18.
57	Recessive loss of function PIGN alleles, including an intragenic deletion with founder effect in La Runion Island, in patients with Fryns syndrome.Eur J Hum Genet. 2018 Mar;26(3):340-349. doi: 10.1038/s41431-017-0087-x. Epub 2018 Jan 12.
58	Congenital diaphragmatic hernia may be associated with 17q12 microdeletion syndrome.Am J Med Genet A. 2015 Jan;167A(1):250-3. doi: 10.1002/ajmg.a.36840. Epub 2014 Nov 25.
59	Xq12q13.1 microduplication encompassing the EFNB1 gene in a boy with congenital diaphragmatic hernia.Eur J Med Genet. 2011 Sep-Oct;54(5):e525-7. doi: 10.1016/j.ejmg.2011.06.011. Epub 2011 Jul 14.
60	A novel RAD21 p.(Gln592del) variant expands the clinical description of Cornelia de Lange syndrome type 4 - Review of the literature. Eur J Med Genet. 2019 Jun;62(6):103526. doi: 10.1016/j.ejmg.2018.08.007. Epub 2018 Aug 17.
61	Pulmonary surfactant protein A, B, and C mRNA and protein expression in the nitrofen-induced congenital diaphragmatic hernia rat model.Pediatr Res. 2003 Nov;54(5):641-52. doi: 10.1203/01.PDR.0000086906.19683.42. Epub 2003 Aug 6.
62	Mouse model reveals the role of SOX7 in the development of congenital diaphragmatic hernia associated with recurrent deletions of 8p23.1.Hum Mol Genet. 2012 Sep 15;21(18):4115-25. doi: 10.1093/hmg/dds241. Epub 2012 Jun 20.
63	Expression of T-box transcription factors 2, 4 and 5 is decreased in the branching airway mesenchyme of nitrofen-induced hypoplastic lungs.Pediatr Surg Int. 2017 Feb;33(2):139-143. doi: 10.1007/s00383-016-4005-z. Epub 2016 Nov 11.