Details of Disease

General Information of Disease (ID: DISD9BBF)

• Disease Name: Hydrops fetalis
• Synonyms: fetal edema; foetal oedema; hydrops fetalis nonimmune; familial non-immune hydrops fetalis; idiopathic hydrops fetalis; generalized fetal edema; fetal hydrops; HF; fetal anasarca; hydrops fetalis; hydrops fetalis (disease); foetal anasarca; foetal hydrops; generalised foetal oedema
• Definition: Hydrops fetalis is a severe and challenging fetal condition usually defined as the excessive accumulation of fetal fluid within the fetal extravascular compartments and body cavities that manifests as edema, pleural and pericardial effusion and ascites. It is the end-stage of a wide variety of disorders. The cause may be immunologic (immune hydrops fetalis, IHF) or non immunologic (non-immune hydrops fetalis, NIHF), depending on the presence or absence of maternal antibodies against fetal red cell antigens (ABO incompatibility or rhesus (Rh) incompatibility).
• Disease Hierarchy:
  DIS7GG31: Developmental defect during embryogenesis
  DISD9BBF: Hydrops fetalis
• Disease Identifiers:
  MONDO ID: MONDO_0015193
  MESH ID: D015160
  UMLS CUI: C0020305
  MedGen ID: 6947
  HPO ID: HP:0001789
  Orphanet ID: 1041
  SNOMED CT ID: 276508000

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 12 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ATP1A2	TT5B6HJ	moderate	Genetic Variation	[1]
NPR1	TTM9IYA	moderate	Biomarker	[2]
SCN2A	TTLJTUF	moderate	Genetic Variation	[3]
AHCY	TTE2KUJ	Strong	Biomarker	[4]
FLT4	TTDCBX5	Strong	Genetic Variation	[5]
FOXC2	TTLBAP1	Strong	Genetic Variation	[6]
FOXP3	TT1X3QF	Strong	Biomarker	[7]
GUSB	TTHS7CM	Strong	Biomarker	[8]
HBA2	TTQO71U	Strong	Genetic Variation	[9]
LIPA	TTS8T1M	Strong	Biomarker	[10]
SGPL1	TT618Q2	Strong	Genetic Variation	[11]
SLC17A5	TTFSUIA	Strong	Biomarker	[12]

This Disease Is Related to 2 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
NMNAT2	DE2HB58	moderate	Biomarker	[13]
PMM2	DEBRX3L	moderate	Genetic Variation	[14]

This Disease Is Related to 16 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
CANT1	OT1TPWQR	moderate	Genetic Variation	[15]
NPC2	OTE9UEJC	moderate	Genetic Variation	[16]
PEX3	OTGZ7ME2	moderate	Biomarker	[17]
RARS2	OT3WLAD8	moderate	Genetic Variation	[18]
RBM38	OTPO8EXU	moderate	Genetic Variation	[19]
SEC23B	OT2NFSIQ	moderate	Biomarker	[20]
SHOC2	OTUNQ2CT	moderate	Genetic Variation	[21]
ASAH1	OT1DNGXL	Strong	Biomarker	[22]
BICD2	OTVJ03NZ	Strong	Biomarker	[23]
CCBE1	OTO4UIDB	Strong	Biomarker	[24]
HADHA	OTO557N2	Strong	Biomarker	[25]
HBA1	OTW2BQF4	Strong	Genetic Variation	[9]
KLF1	OT1FK08U	Strong	Genetic Variation	[26]
NEU1	OTH9BY8Y	Strong	Biomarker	[27]
RIT1	OTVNOGOH	Strong	Genetic Variation	[28]
TALDO1	OTDKV2S2	Strong	Genetic Variation	[29]

References

• [1] Biallelic loss of function variants in ATP1A2 cause hydrops fetalis, microcephaly, arthrogryposis and extensive cortical malformations. Eur J Med Genet. 2020 Jan;63(1):103624. doi: 10.1016/j.ejmg.2019.01.014. Epub 2019 Jan 25.
• [2] Importance of Endogenous Atrial and Brain Natriuretic Peptides in Murine Embryonic Vascular and Organ Development.Endocrinology. 2016 Jan;157(1):358-67. doi: 10.1210/en.2015-1344. Epub 2015 Oct 30.
• [3] Noninvasive prenatal detection of hemoglobin Bart hydrops fetalis via maternal plasma dispensed with parental haplotyping using the semiconductor sequencing platform.Am J Obstet Gynecol. 2020 Feb;222(2):185.e1-185.e17. doi: 10.1016/j.ajog.2019.07.044. Epub 2019 Aug 5.
• [4] S-adenosylhomocysteine hydrolase deficiency: two siblings with fetal hydrops and fatal outcomes.J Inherit Metab Dis. 2010 Dec;33(6):705-13. doi: 10.1007/s10545-010-9171-x. Epub 2010 Sep 18.
• [5] Sporadic in utero generalized edema caused by mutations in the lymphangiogenic genes VEGFR3 and FOXC2.J Pediatr. 2009 Jul;155(1):90-3. doi: 10.1016/j.jpeds.2009.02.023. Epub 2009 Apr 25.
• [6] From childhood onset lymphedema to fatal fetal hydrops: Possible modifying genes for a FOXC2 mutation.Lymphology. 2018;51(2):85-88.
• [7] Identification of a novel nonsense mutation in the FOXP3 gene in a fetus with hydrops--Expanding the phenotype of IPEX syndrome.Am J Med Genet A. 2016 Jan;170A(1):226-32. doi: 10.1002/ajmg.a.37401. Epub 2015 Sep 23.
• [8] Nonimmune fetal hydrops and lysosomal storage disease: the finding of vacuolated lymphocytes in ascitic fluid in two cases.Prenat Diagn. 2014 Feb;34(2):199-201. doi: 10.1002/pd.4274. Epub 2013 Nov 28.
• [9] Validation of the immunochromatographic strip for -thalassemia screening: a multicenter study.Transl Res. 2015 Jun;165(6):689-95. doi: 10.1016/j.trsl.2014.10.013. Epub 2014 Nov 5.
• [10] Isolated fetal ascites caused by Wolman disease.Ultrasound Obstet Gynecol. 2003 Mar;21(3):297-8. doi: 10.1002/uog.73.
• [11] A novel mutation in sphingosine-1-phosphate lyase causing congenital brain malformation.Brain Dev. 2018 Jun;40(6):480-483. doi: 10.1016/j.braindev.2018.02.008. Epub 2018 Mar 2.
• [12] Recurrent nonimmune hydrops fetalis: a rare presentation of sialic acid storage disease.Genet Couns. 1999;10(3):277-84.
• [13] Severe biallelic loss-of-function mutations in nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) in two fetuses with fetal akinesia deformation sequence.Exp Neurol. 2019 Oct;320:112961. doi: 10.1016/j.expneurol.2019.112961. Epub 2019 May 25.
• [14] Pericardial and abdominal fluid accumulation in congenital disorder of glycosylation type Ia.Mol Genet Metab. 2008 Aug;94(4):481-484. doi: 10.1016/j.ymgme.2008.05.005. Epub 2008 Jun 20.
• [15] Desbuquois dysplasia type I and fetal hydrops due to novel mutations in the CANT1 gene.Eur J Hum Genet. 2011 Nov;19(11):1133-7. doi: 10.1038/ejhg.2011.101. Epub 2011 Jun 8.
• [16] An uncommon inheritance pattern in Niemann-Pick disease type C: identification of probable paternal germline mosaicism in a Mexican family.BMC Neurol. 2016 Aug 22;16(1):147. doi: 10.1186/s12883-016-0649-5.
• [17] Zellweger syndrome with unusual findings: non-immune hydrops fetalis, dermal erythropoiesis and hypoplastic toe nails.J Inherit Metab Dis. 2009 Dec;32 Suppl 1:S345-8. doi: 10.1007/s10545-009-9010-0. Epub 2009 Dec 23.
• [18] Neuropathologic Characterization of Pontocerebellar Hypoplasia Type 6 Associated With Cardiomyopathy and Hydrops Fetalis and Severe Multisystem Respiratory Chain Deficiency due to Novel RARS2 Mutations.J Neuropathol Exp Neurol. 2015 Jul;74(7):688-703. doi: 10.1097/NEN.0000000000000209.
• [19] RNA Binding Protein RBM38 Regulates Expression of the 11-Kilodalton Protein of Parvovirus B19, Which Facilitates Viral DNA Replication.J Virol. 2018 Mar 28;92(8):e02050-17. doi: 10.1128/JVI.02050-17. Print 2018 Apr 15.
• [20] CDAII presenting as hydrops foetalis: molecular characterization of two cases.Blood Cells Mol Dis. 2010 Jun 15;45(1):20-2. doi: 10.1016/j.bcmd.2010.03.005. Epub 2010 Apr 9.
• [21] Hydrops fetalis in a preterm newborn heterozygous for the c.4A>G SHOC2 mutation.Am J Med Genet A. 2014 Apr;164A(4):1015-20. doi: 10.1002/ajmg.a.36376. Epub 2014 Jan 23.
• [22] Evidence for clinical, genetic and biochemical variability in spinal muscular atrophy with progressive myoclonic epilepsy.Clin Genet. 2014 Dec;86(6):558-63. doi: 10.1111/cge.12307. Epub 2013 Nov 21.
• [23] In-frame de novo mutation in BICD2 in two patients with muscular atrophy and arthrogryposis.Cold Spring Harb Mol Case Stud. 2018 Oct 1;4(5):a003160. doi: 10.1101/mcs.a003160. Print 2018 Oct.
• [24] Linkage and sequence analysis indicate that CCBE1 is mutated in recessively inherited generalised lymphatic dysplasia.Hum Genet. 2010 Feb;127(2):231-41. doi: 10.1007/s00439-009-0766-y. Epub 2009 Nov 13.
• [25] Long-chain fatty acid oxidation during early human development.Pediatr Res. 2005 Jun;57(6):755-9. doi: 10.1203/01.PDR.0000161413.42874.74. Epub 2005 Apr 21.
• [26] Gene expression in blood from an individual with -thalassemia: An RNA sequence analysis.Mol Genet Genomic Med. 2019 Jul;7(7):e00740. doi: 10.1002/mgg3.740. Epub 2019 May 27.
• [27] Prenatal diagnosis and fetal pathology in a Turkish family harboring a novel nonsense mutation in the lysosomal alpha-N-acetyl-neuraminidase (sialidase) gene.Hum Genet. 2001 Oct;109(4):421-8. doi: 10.1007/s004390100592.
• [28] Two cases of RIT1 associated Noonan syndrome: Further delineation of the clinical phenotype and review of the literature.Am J Med Genet A. 2016 Jul;170(7):1874-80. doi: 10.1002/ajmg.a.37657. Epub 2016 Apr 25.
• [29] Transaldolase deficiency: a new cause of hydrops fetalis and neonatal multi-organ disease.J Pediatr. 2006 Nov;149(5):713-7. doi: 10.1016/j.jpeds.2006.08.016.