Neural tube defects (NTDs) are one of the most common birth defects, occurring in approximately one in 1,000 live births in the United States. An NTD is an opening in the spinal cord or brain that occurs very early in human development. The early spinal cord of the embryo begins as a flat region, which rolls into a tube (the neural tube) 28 days after the baby is conceived. When the neural tube does not close completely, an NTD develops. NTDs develop before most women know they are even pregnant.
There are two types of NTDs. The most common type are called the open NTDs. Open NTDs occur when the brain and/or spinal cord are exposed at birth through a defect in the skull or vertebrae (back bones). Examples of open NTDs are spina bifida (myelomeningocele), anencephaly, and encephalocele. Rarer types of NTDs are called closed NTDs. Closed NTDs occur when the spinal defect is covered by skin. Common examples of closed NTDs are lipomyelomeningocele, lipomeningocele, and tethered cord.
Lastly, spina bifida occulta (SBO) is potentially another form of an NTD in which there is a typically benign (or non-symptom-causing) bony change in one or more vertebrae, but not involving the nerves within the spinal column. The incidence of SBO is not well defined; however, it is more common than the NTDs described above. The cause and potential similarities or link to NTDs has not been established.
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Researchers have found that 50-70% of NTDs can be prevented when women supplement their diet with folic acid, a water-soluble B vitamin. The Centers for Disease Control (CDC) recommends all women of childbearing age eat a diet high in folic acid or take a multivitamin with 400 micrograms of folic acid each day, especially one month prior to conception through the first three months of pregnancy. This dosage is the amount found in most over-the-counter multivitamins. However, women who have had a previous NTD pregnancy are recommended to take an even higher dosage of folic acid prior to planning a pregnancy. They should increase the daily dose of folic acid from 400 micrograms to 4,000 micrograms (4 milligrams), one month prior to conception through the first three months of pregnancy. The 4,000 micrograms of folic acid should only be obtained through a prescription from the doctor.
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Most NTDs can be detected during pregnancy by one of three different prenatal tests:
- Maternal Serum Alpha Fetoprotein (MSAFP), a screening test that is performed on a pregnant woman's blood at approximately 16-18 weeks of pregnancy
- High Resolution Ultrasound, which may detect an NTD visually after approximately 18 weeks of pregnancy. Some severe forms of NTDs such as anencephaly, may be detected earlier than 16 weeks
- Amniocentesis, a test that samples the amniotic fluid (fluid that surrounds the baby) after 15 weeks of pregnancy.
There are various risks (such as miscarriage) and benefits (such as advance preparation for any special medical care a baby with an NTD will need after delivery) to each of these tests. A genetic counselor or other health care provider should be consulted to explain in detail each procedure, their risks and benefits, and other options available
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Neural tube defects are considered a complex disorder because they are caused by a combination of multiple genes and multiple environmental factors. Known environmental factors include folic acid, maternal insulin dependent diabetes, and maternal use of certain anticonvulsant (antiseizure) medications. While only a few environmental factors have been characterized, many different studies provide evidence that NTDs have a genetic component in their development. Studies of twins with NTDs have shown both identical twins have NTDs more than both fraternal twins. Studies of families show that the chance of having a second family member born with an NTD after one child is born with an NTD increases. For example, the general population’s chance of having an NTD is approximately 0.1% (1 in 1000). However, once a couple has one child with an NTD, their chance of having a second child with an NTD is increased to approximately 2-5%. Further studies have shown evidence for a genetic pattern of inheritance for NTDs.
NTDs are a feature (or symptom) of known genetic syndromes, such as trisomy 13, trisomy 18, certain chromosome rearrangements, and Meckel-Gruber syndrome.
The Duke Center for Human Genetics is currently conducting a genetic study called “The Hereditary Basis of Neural Tube Defects,” to determine the causes of NTDs. By studying families with NTDs, we hope to identify the genes that contribute to the development of an NTD. We hope this research will allow us to better understand the genetic and environmental causes of NTDs, which will eventually lead to more accurate genetic counseling and risk assessment, improved treatments, better prevention methods, and, possibly, a cure.
As a part of our overall NTD genetic study, we are also conducting sub-studies, including investigations into the genetics of anencephaly and closed NTDs.
- Anencephaly is one of the most severe, fatal forms of an NTD. Anencephaly is defined as the incomplete formation of the skull, which is at the top of the neural tube. We are particularly interested in helping uncover the cause(s) of anencephaly, in the hopes of helping families understand this devastating disorder.
- Closed NTDs, such as lipo(myelo)meningocele, lipomeningocele, and tethered cord occur when skin has grown over the NTD. The genetics of closed NTDs are not currently understood. For many years, researchers have assumed that the information about myelomeningocele is the same for the closed NTDs. The aim of this sub-study is to determine if the same genetic factors that contribute to causing open neural tube defects, such as myelomeningocele, are also responsible for contributing to the cause of closed NTDs.
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A project of this magnitude requires the efforts of many. These experienced CHG researcherswith the help of participating familiescontinue to search for genes that cause NTDs.
| Allison Ashley-Koch, PhD
||Co-Principal Investigator and Genetic Epidemiologist
| Simon Gregory, PhD
||Co-Principal Investigator and Molecular Geneticist
|Gordon Worley, MD
|David Enterline, MD
|Heidi Cope, MS
||Genetic Counselor, Study Coordinator
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Published research findings in peer-reviewed scientific journals are one way that progress is measured. The efforts of everyone, most importantly the families, will enable us to unravel the genetics of NTDs.
Neural Tube Defect Research Publications
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The Duke Center for Human Genetics is currently only enrolling families in which a current pregnancy has been diagnosed with anencephaly or acrania. Please contact the study coordinator if you have questions about the research or would like to learn more about participating in the study.
NTD Study Coordinator
Heidi Cope, MS, CGC
Phone: (919) 684-0655
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NTD Research Newsletter
News About NTD Research, 2012
News About NTD Research, Summer 2010
News About NTD Research, Winter 2009
News About NTD Research, Summer 2006
News About NTD Research, Winter 2004
NTD Study Introduction
NTD Support Groups and Information Sources
Spina Bifida Association of America (SBAA)
4590 MacArthur Blvd, NW Suite 250
Washington, DC 20007-4226
Fax: (202) 944-3295
Spina Bifida and Hydrocephalus Association of Canada (SBHAC)
220-388 Donald Street
Winnipeg, Manitoba R3B 2J4
Fax: (204) 925-3654
Lipomyelomeningocele Family Support Network (LFSN)
Hydrocephalus Support Group, Inc. (HSG, Inc.)
PO Box 4236
Chesterfield, MO 63006-4236
Phone: (314) 532-8228
FDA Proposes Folic Acid Fortification
US Food and Drug Administration
Office of Public Affairs
February 29, 1996
Centers for Disease Control
National Center on Birth Defects and Developmental Disabilities
1600 Clifton Road
Atlanta, GA 30333
Phone: (800) 311-3435
Phone: (404) 639-3534
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