FVS
MCID: VLP002
MIFTS: 41

Valproate Embryopathy (FVS)

Categories: Fetal diseases, Rare diseases

Aliases & Classifications for Valproate Embryopathy

MalaCards integrated aliases for Valproate Embryopathy:

Name: Valproate Embryopathy 56
Fetal Valproate Syndrome 56 12 52 58 15 71
Fetal Valproic Acid Syndrome 12 52 58
Fvs 56 52
Valproate Embryopathy, Susceptibility to 56
Susceptibility to Valproate Embryopathy 52
Valproic Acid Antenatal Infection 43
Fetal Valproate Syndrome; Fvs 56
Valproic Acid Embryopathy 52

Characteristics:

Orphanet epidemiological data:

58
fetal valproate syndrome
Inheritance: Not applicable; Age of onset: Antenatal,Neonatal;

Classifications:

Orphanet: 58  
Developmental anomalies during embryogenesis
Teratologic disorders


External Ids:

Disease Ontology 12 DOID:0060471
OMIM 56 609442
MeSH 43 C536525
NCIt 49 C98930
SNOMED-CT 67 17231009
MESH via Orphanet 44 C536525
ICD10 via Orphanet 33 Q86.8
UMLS via Orphanet 72 C0236026
Orphanet 58 ORPHA1906
UMLS 71 C0236026

Summaries for Valproate Embryopathy

NIH Rare Diseases : 52 Fetal valproate syndrome (FVS) may occur if a developing baby is exposed to valproic acid during pregnancy. Valproic acid, also known as valproate, is a medication that is often used to treat epilepsy , bipolar disorder , and migraines . Many babies who are exposed to this medication during pregnancy are born healthy with normal growth and development. However, studies have found that women who take valproate during pregnancy have a greater chance of having a baby with a major birth defect or other health problem. Symptoms of FVS vary but may include characteristic facial features, spina bifida , congenital heart defects , cleft lip and/or cleft palate , genital abnormalities, skeletal abnormalities, and developmental delay . A child exposed to valproic acid may be at a higher risk for learning and behavioral problems. Although there is no cure for FVS, many of the possible signs and symptoms of FVS do have treatments or therapies available. Early intervention programs may also be helpful. The U.S. Food and Drug Administration (FDA) advises that valproate and related products should not be taken by women for the prevention of migraine headaches during pregancy. With regard to valproate use in pregnant women with epilepsy or bipolar disorder, valproate products should only be prescribed if other medications are not effective in treating the condition or are otherwise unacceptable. However, it is important to note that women who are pregnant and taking a valproate medication should not stop their medication but should talk to their doctor or other trusted medical professional immediately. Stopping valproate treatment suddenly can cause serious and life-threatening medical problems to the woman or her baby. For example, the sudden discontinuation of valproate in pregnant women with seizures can result in persistent seizures, which can cause harm, including death, to the mother and/or the unborn baby. The FDA suggests a pregnant woman taking valproate or other anti-seizure medication should talk to her doctor or other trusted medical professional about registering with the North American Antiepileptic Drug Pregnancy Registry. The purpose of this registry is to collect information about the safety of anti-seizure medications during pregnancy. A pregnant woman taking anti-seizure medication can enroll in this registry by calling 1-888-233-2334. You can read more about the registry on the North American AED (Antiepileptic Drug) Pregnancy Registry website . It is suggested that physicians refer pregnant patients who are using valproate to register for an antiepileptic drug registration program called North American Antiepileptic Drug (NAAED) Pregnancy Registry: http://www.aedpregnancyregistry.org/

MalaCards based summary : Valproate Embryopathy, also known as fetal valproate syndrome, is related to seizure disorder and factor v and factor viii, combined deficiency of, 2. An important gene associated with Valproate Embryopathy is ACSM6 (Acyl-CoA Synthetase Medium Chain Family Member 6), and among its related pathways/superpathways are Ectoderm Differentiation and Butanoate metabolism. Affiliated tissues include heart, t cells and thyroid, and related phenotypes are short nose and long philtrum

Disease Ontology : 12 A syndrome characterized by distinctive facial appearance, a cluster of minor and major anomalies and central nervous system dysfunction.

OMIM : 56 All antiepileptic drugs are potential teratogens. Anticonvulsant treatment during pregnancy presents the challenge of balancing between optimal treatment for seizure control and possible harmful fetal effects. One of the best delineated examples of harmful fetal effects is the fetal valproate syndrome (FVS), comprising typical facial features, developmental delay, and a variety of malformations such as neural tube defects, cardiac and gastrourinary malformations, and limb defects (Winter et al., 1987; Ardinger et al., 1988; Clayton-Smith and Donnai, 1995). (609442)

Related Diseases for Valproate Embryopathy

Diseases related to Valproate Embryopathy via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 222)
# Related Disease Score Top Affiliating Genes
1 seizure disorder 29.7 NLGN1 MECP2
2 factor v and factor viii, combined deficiency of, 2 12.2
3 factor v and factor viii, combined deficiency of, 1 11.5
4 thrombophilia 10.5
5 thrombophilia due to thrombin defect 10.5
6 thrombophilia due to activated protein c resistance 10.5
7 severe combined immunodeficiency 10.4
8 ovarian cancer 10.3
9 thrombosis 10.3
10 neuroblastoma 10.3
11 hepatitis c virus 10.2
12 leukemia 10.2
13 adenocarcinoma 10.2
14 b-cell lymphoma 10.2
15 neural tube defects 10.2
16 huntington disease 10.2
17 rabies 10.2
18 viral hepatitis 10.2
19 melanoma 10.2
20 colorectal cancer 10.2
21 hepatocellular carcinoma 10.2
22 human immunodeficiency virus type 1 10.2
23 tetanus 10.2
24 breast cancer 10.1
25 mesothelioma, malignant 10.1
26 factor v deficiency 10.1
27 lung cancer susceptibility 3 10.1
28 helix syndrome 10.1
29 adult t-cell leukemia 10.1
30 diphtheria 10.1
31 prion disease 10.1
32 t-cell leukemia 10.1
33 placenta disease 10.1
34 pulmonary embolism 10.1
35 cytokine deficiency 10.1
36 autism 10.1
37 hypospadias 10.1
38 craniosynostosis 10.1
39 echolalia 10.1 NLGN3 MECP2
40 pitt-hopkins-like syndrome 1 10.1 NLGN3 MECP2
41 autoimmune disease 10.1
42 bladder cancer 10.1
43 myasthenia gravis 10.1
44 osteogenic sarcoma 10.1
45 protein s deficiency 10.1
46 plasmacytoma 10.1
47 thyroiditis 10.1
48 polycythemia 10.1
49 optic nerve hypoplasia, bilateral 10.0
50 septooptic dysplasia 10.0

Graphical network of the top 20 diseases related to Valproate Embryopathy:



Diseases related to Valproate Embryopathy

Symptoms & Phenotypes for Valproate Embryopathy

Human phenotypes related to Valproate Embryopathy:

58 31 (show all 8)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 short nose 58 31 hallmark (90%) Very frequent (99-80%) HP:0003196
2 long philtrum 58 31 hallmark (90%) Very frequent (99-80%) HP:0000343
3 epicanthus 58 31 hallmark (90%) Very frequent (99-80%) HP:0000286
4 narrow mouth 58 31 hallmark (90%) Very frequent (99-80%) HP:0000160
5 depressed nasal ridge 58 31 hallmark (90%) Very frequent (99-80%) HP:0000457
6 thin vermilion border 58 31 hallmark (90%) Very frequent (99-80%) HP:0000233
7 downturned corners of mouth 58 31 hallmark (90%) Very frequent (99-80%) HP:0002714
8 omphalocele 58 31 hallmark (90%) Very frequent (99-80%) HP:0001539

Clinical features from OMIM:

609442

MGI Mouse Phenotypes related to Valproate Embryopathy:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.97 ACSM4 BSND EIF4H ENAH MECP2 NLGN1
2 growth/size/body region MP:0005378 9.85 ACSM4 BSND EIF4H ENAH MECP2 NLGN1
3 craniofacial MP:0005382 9.73 ACSM4 EIF4H MECP2 OTX2 RANBP1 VAX2
4 nervous system MP:0003631 9.65 ACSM4 BSND EIF4H ENAH MECP2 NLGN1
5 taste/olfaction MP:0005394 8.8 ACSM4 NLGN3 OTX2

Drugs & Therapeutics for Valproate Embryopathy

Search Clinical Trials , NIH Clinical Center for Valproate Embryopathy

Cochrane evidence based reviews: valproic acid antenatal infection

Genetic Tests for Valproate Embryopathy

Anatomical Context for Valproate Embryopathy

MalaCards organs/tissues related to Valproate Embryopathy:

40
Heart, T Cells, Thyroid, Kidney, Lung, B Cells, Eye

Publications for Valproate Embryopathy

Articles related to Valproate Embryopathy:

(show top 50) (show all 81)
# Title Authors PMID Year
1
Valproate embryopathy in three sets of siblings: further proof of hereditary susceptibility. 61 56
12196666 2002
2
Fetal valproate syndrome. 61 56
8544193 1995
3
Verification of the fetal valproate syndrome phenotype. 61 56
3125743 1988
4
Fetal valproate syndrome: is there a recognisable phenotype? 61 56
3123693 1987
5
A mouse model for valproate teratogenicity: parental effects, homeotic transformations, and altered HOX expression. 56
10607833 2000
6
Valproic acid in pregnancy: how much are we endangering the embryo and fetus? 52
19490988 2009
7
A Case Series of Fetal Valproate Syndrome in the Republic of Crimea. 61
31831992 2019
8
Intellectual functioning in clinically confirmed fetal valproate syndrome. 61
30453023 2019
9
Fetal valproate syndrome: the Irish experience. 61
29396778 2018
10
Fetal valproate syndrome as a phenocopy of Kleefstra syndrome. 61
30151876 2018
11
Fetal Valproate Syndrome - Still a Problem Today! 61
29073690 2017
12
Activities of Proline-Specific Proteinases in the Serum and Cerebrospinal Fluid of Rats with the Fetal Valproate Syndrome. 61
28948551 2017
13
Fetal Valproate Syndrome. 61
27422007 2017
14
Prenatal sonographic diagnosis of fetal valproate syndrome: a case report. 61
27809899 2016
15
New findings in fetal valproate syndrome: hiatal hernia, gastric volvulus and ectopic kidney. 61
27012229 2016
16
Effects of developmental alcohol and valproic acid exposure on play behavior of ferrets. 61
27208641 2016
17
Fetal Valproate Syndrome with Limb Defects: An Indian Case Report. 61
28003925 2016
18
[Coarctation of the aorta in children in the 10-year epidemiological study: diagnostic and therapeutic consideration]. 61
25906542 2015
19
Middle and inner ear malformations in two siblings exposed to valproic acid during pregnancy: a case report. 61
25216807 2014
20
Difficult airway in an infant with fetal valproate syndrome. 61
24292219 2014
21
Neurodevelopmental and esthetic results in children after surgical correction of metopic suture synostosis: a single institutional experience. 61
24337567 2014
22
Fetal valproate syndrome. 61
25400349 2014
23
Is coloboma a feature of fetal valproate syndrome? 61
24263622 2014
24
Valproic acid silencing of ascl1b/Ascl1 results in the failure of serotonergic differentiation in a zebrafish model of fetal valproate syndrome. 61
24135485 2014
25
An anomalous left superior venacava draining into left atrium in association with fetal valproate syndrome. 61
22678520 2013
26
Epigenetic changes and disturbed neural development in a human embryonic stem cell-based model relating to the fetal valproate syndrome. 61
22723015 2012
27
Valproate-induced teratogenesis in Japanese rice fish (Oryzias latipes) embryogenesis. 61
22249148 2012
28
Valproic acid inhibits neural progenitor cell death by activation of NF-κB signaling pathway and up-regulation of Bcl-XL. 61
21722408 2011
29
Severe fetal valproate syndrome: combination of complex cardiac defect, multicystic dysplastic kidney, and trigonocephaly. 61
21291342 2011
30
Behavioral and molecular changes in the mouse in response to prenatal exposure to the anti-epileptic drug valproic acid. 61
20603192 2010
31
Fetal valproate syndrome in a 2-month-old male infant. 61
20427941 2010
32
Aplasia cutis congenita: three cases with three different underlying etiologies. 61
20112612 2009
33
A case of fetal valproate syndrome with new features expanding the phenotype. 61
19618023 2009
34
A case of fetal valproate syndrome with new features expanding the phenotype. 61
19198722 2009
35
Neurodevelopmental delay in children exposed to antiepileptic drugs in utero: a critical review directed at structural study-bias. 61
18479711 2008
36
Omphalocele and gastroschisis and associated malformations. 61
18386803 2008
37
Syndromes, disorders and maternal risk factors associated with neural tube defects (I). 61
18400576 2008
38
Pregnancy outcome after in utero exposure to valproate : evidence of dose relationship in teratogenic effect. 61
18336060 2008
39
Early intervention for the ocular and neurodevelopmental sequelae of Fetal Valproate Syndrome. 61
17688650 2007
40
A clinical algorithm of prenatal diagnosis of Radial Ray Defects with two and three dimensional ultrasound. 61
17533626 2007
41
Syndromes and disorders associated with omphalocele (III): single gene disorders, neural tube defects, diaphragmatic defects and others. 61
17638618 2007
42
Fetal valproate syndrome. 61
17090909 2006
43
[Embryopathy due to valproic acid with severe malformations in the central nervous system]. 61
16575769 2006
44
A case of fetal anticonvulsant syndrome with severe bilateral upper limb defect. 61
16676441 2006
45
Valproate embryopathy: clinical and cognitive profile in 5 siblings. 61
15669094 2005
46
[Fetal valproate syndrome]. 61
14600761 2003
47
[Fetal valproate syndrome]. 61
14508573 2003
48
Patent ductus arteriosus in fetal valproate syndrome. 61
14510093 2003
49
Multiple congenital malformations including generalized hypertrichosis with gum hypertrophy in a child exposed to valproic acid in utero. 61
14577673 2003
50
Nuchal edema as the first sign of fetal valproate syndrome. 61
12224082 2002

Variations for Valproate Embryopathy

Expression for Valproate Embryopathy

Search GEO for disease gene expression data for Valproate Embryopathy.

Pathways for Valproate Embryopathy

Pathways related to Valproate Embryopathy according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.96 VAX2 NLGN1 MECP2
2
Show member pathways
10.54 ACSM6 ACSM4

GO Terms for Valproate Embryopathy

Cellular components related to Valproate Embryopathy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 postsynapse GO:0098794 9.33 NLGN3 NLGN1 MECP2
2 excitatory synapse GO:0060076 9.26 NLGN3 NLGN1
3 spanning component of membrane GO:0089717 8.96 NLGN3 NLGN1
4 asymmetric, glutamatergic, excitatory synapse GO:0098985 8.62 NLGN3 NLGN1

Biological processes related to Valproate Embryopathy according to GeneCards Suite gene sharing:

(show all 17)
# Name GO ID Score Top Affiliating Genes
1 visual learning GO:0008542 9.57 NLGN3 MECP2
2 synapse organization GO:0050808 9.56 NLGN3 NLGN1
3 synaptic vesicle endocytosis GO:0048488 9.55 NLGN3 NLGN1
4 acyl-CoA metabolic process GO:0006637 9.54 ACSM6 ACSM4
5 regulation of NMDA receptor activity GO:2000310 9.52 NLGN3 NLGN1
6 positive regulation of excitatory postsynaptic potential GO:2000463 9.51 NLGN3 NLGN1
7 regulation of AMPA receptor activity GO:2000311 9.49 NLGN3 NLGN1
8 positive regulation of synaptic transmission, glutamatergic GO:0051968 9.48 NLGN3 NLGN1
9 neuron cell-cell adhesion GO:0007158 9.46 NLGN3 NLGN1
10 presynapse assembly GO:0099054 9.43 NLGN3 NLGN1
11 synapse assembly GO:0007416 9.43 NLGN3 NLGN1 MECP2
12 presynaptic membrane assembly GO:0097105 9.4 NLGN3 NLGN1
13 postsynaptic membrane assembly GO:0097104 9.37 NLGN3 NLGN1
14 negative regulation of dendritic spine morphogenesis GO:0061002 9.32 NLGN3 NLGN1
15 positive regulation of synaptic vesicle clustering GO:2000809 9.16 NLGN3 NLGN1
16 long-term synaptic potentiation GO:0060291 9.13 NLGN3 NLGN1 MECP2
17 regulation of respiratory gaseous exchange by neurological system process GO:0002087 8.8 NLGN3 NLGN1 MECP2

Molecular functions related to Valproate Embryopathy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 acyl-CoA ligase activity GO:0003996 9.32 ACSM6 ACSM4
2 neurexin family protein binding GO:0042043 9.26 NLGN3 NLGN1
3 butyrate-CoA ligase activity GO:0047760 9.16 ACSM6 ACSM4
4 fatty acid ligase activity GO:0015645 8.96 ACSM6 ACSM4
5 fatty-acyl-CoA synthase activity GO:0004321 8.62 ACSM6 ACSM4

Sources for Valproate Embryopathy

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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