Rare Rheumatology News

Disease Profile

Fetal valproate syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Antenatal

ICD-10

Q86.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Valproic acid embryopathy; Susceptibility to valproate embryopathy; FVS;

Categories

Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases; Mouth Diseases

Summary

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.[1][2][3]

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.[4]

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.[4]

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: https://www.aedpregnancyregistry.org/

Symptoms

Many babies who are exposed to valproic acid during pregnancy are born healthy and do not have fetal valproate syndrome (FVS). However, studies have found that pregnant women who take valproic acid have a greater chance of having a baby with a major or minor birth defect. When present, the signs and symptoms of FVS can vary significantly from baby to baby. Symptoms may include:[1][2][3]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Depressed nasal ridge
Flat nose
Recessed nasal ridge

[ more ]

0000457
Downturned corners of mouth
Downturned corners of the mouth
Downturned mouth

[ more ]

0002714
Epicanthus
Eye folds
Prominent eye folds

[ more ]

0000286
Long philtrum
0000343
Narrow mouth
Small mouth
0000160
Omphalocele
0001539
Short nose
Decreased length of nose
Shortened nose

[ more ]

0003196
Thin vermilion border
Decreased volume of lip
Thin lips

[ more ]

0000233

Cause

Fetal valproate syndrome (FVS) may be caused by exposure of a developing baby to valproic acid when a pregnant woman takes it during pregnancy. The risk for the baby to have one or more of the major birth defects associated with FVS is highest if exposure occurs during the first trimester, especially if the mother is taking doses greater than 800 mg/day. This is because the brain and spinal cord, heart, facial features, bones, muscles, and genitals all begin to develop in the first trimester.[2][3]

Diagnosis

Fetal valproate syndrome (FVS) is often suspected in an infant who has one or more of the signs and symptoms associated with FVS and whose mother reports having taken valproic acid during the pregnancy. There is no test that can confirm the diagnosis of FVS, instead other possible causes of the signs and symptoms seen in the baby must be ruled out.[1]

Treatment

The treatment of fetal valproate syndrome (FVS) is based on the signs and symptoms present in each baby or child. Management often involves a team of medical specialists and may include:[1][2] 

  • Birth defects such as spina bifida and other neural tube defects, congenital heart defects, and cleft lip and/or cleft palate may require surgery shortly after birth
  • Long-term follow-up to detect and treat early behavioral or developmental issues
  • Early speech therapy, occupational therapy, and/or physical therapy
  • Extra assistance at school 

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Learn more

    These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

    Where to Start

    • MotherToBaby is a service of the non-profit Organization of Teratology Information Specialists (OTIS), a leading authority on information regarding the safety of medications and other exposures during pregnancy and breastfeeding. They can be reached directly by calling 1-866-626-6847.
    • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

      In-Depth Information

      • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
      • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
      • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
      • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
      • PubMed is a searchable database of medical literature and lists journal articles that discuss Fetal valproate syndrome. Click on the link to view a sample search on this topic.

        References

        1. Fetal valproate syndrome. Orphanet. November 2015; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=1906.
        2. Mutlu-Albayrak H, Bulut C, Çaksen H. Fetal Valproate Syndrome. Pediatr Neonatol. June 2016; pii: S1875-9572(16):300072-9. https://www.pediatr-neonatol.com/article/S1875-9572(16)30072-9/fulltext.
        3. Ornoy A.. Valproic acid in pregnancy: how much are we endangering the embryo and fetus. Reprod Toxicol. July 2009; 28(1):1-10. https://www.ncbi.nlm.nih.gov/pubmed/19490988.
        4. FDA Drug Safety Communication: Valproate Anti-seizure Products Contraindicated for Migraine Prevention in Pregnant Women due to Decreased IQ Scores in Exposed Children. US Food and Drug Administration (FDA). February, 2016; https://www.fda.gov/Drugs/DrugSafety/ucm350684.htm.

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