Disorders

Neural Tube Defects (NTDs)

• What are Neural Tube Defects (NTDs)?
  
  • NTD Prevention
    
  • NTD Detection
    
• Genetics and Neural Tube Defects
  
• Neural Tube Defects Research Review
  
• CHG Neural Tube Defects Publications
  
• Neural Tube Defects Study Participation
  
• Additional Neural Tube Defects Information
  

What are Neural Tube Defects (NTDs)?

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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NTD Prevention

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 0.4mg 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 0.4mg to 4.0mg, one month prior to conception through the first three months of pregnancy. The 4.0mg of folic acid should only be obtained through a prescription from the doctor.

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NTD Detection

Most NTDs can be detected during pregnancy by one of three different prenatal tests:

1. Maternal Serum Alpha Fetoprotein (MSAFP), a screening test that is performed on a pregnant woman's blood at approximately 16-18 weeks of pregnancy
   
   
2. 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
   
   
3. 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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Genetics and Neural Tube Defects

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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Neural Tube Defects Research Review

NTDs are one of the most common birth defects, though their causes are not well understood. The formation of the neural tube during development is a complex process, and the goal of our project is to discover the genetic and environmental factors that contribute to NTDs. One major step in research is to gather data on a large number of families. Currently, the Center for Human Genetics (CHG) has enrolled more than 1200 families. We will need to enroll another 500-1000 families before some of the laboratory studies can be completed. We continue to collaborate with Myelodysplasia clinics around the country, presenting information at local and national Spina Bifida Association of America conferences, and speaking with families interested in the study.

In the laboratory, our goal is to find genes that cause or contribute to NTDs. There are two major strategies scientists are using:

• genome scan – systematically searching each chromosome, looking for areas which may harbor genes that cause or contribute to NTDs
  
  
• candidate gene analysis – studying genes of known function that could potentially be involved in neural tube development. Examples of candidate genes include the many genes involved in the folic acid metabolism pathway, genes known to cause NTDs in animals, and genes involved in chromosomal rearrangements in individuals who also have NTDs.

Neural Tube Defect Study Team

A project of this magnitude requires the efforts of many. These experienced CHG researchers—with the help of interested families—continue to search for genes that cause NTDs.

Study Collaborators

• Alabama Children’s Rehabilitation Services
  
• Carolinas Medical Center
  
• Children’s Hospital of Richmond
  
• Children’s Hospital of Wisconsin
  
• Duke University Medical Center
  
• East Carolina University
  
• Fullerton Genetics
  
• Indiana University
  
• Loyola University
  
• Northwestern University/Memorial Children’s Hospital
  
• Oregon Health and Science University
  
• Park Nicolette Hospital
  
• Shriners Hospital for Children
  
• University at Buffalo/Women and Children’s Hospital of Buffalo
  
• University of Alabama at Birmingham
  
• University of North Carolina at Chapel Hill
  
• University of Utah
  
• University of Wisconsin Hospital and Clinics
  
• Wake Forest University School of Medicine
  
• Washington University
  
• West Virginia University
  

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CHG Neural Tube Defect Publications

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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Neural Tube Defect Study Participation

The Duke Center for Human Genetics is currently recruiting families in which one or more family members have any type of neural tube defect, including spina bifida (meningocele or myelomeningocele), anencephaly, encephalocele, lipomyelomeningocele, lipomeningocele, tethered cord, iniencephaly, craniorachischisis, or split cord malformation.

Study Coordinators

Debbie Siegel		Study Coordinator
Heidi Cope, MS, CGC		Genetic Counselor

Participation in the research is free and does not require travel to Duke University Medical Center.

Study participation includes the following:

• A telephone interview, at the convenience of the family, to draw the family tree and discuss pregnancy and medical information.
  
  
• Permission for the research team to review the medical records of the family member(s) with an NTD to confirm the type and level of the lesion.
  
  
• Obtaining blood samples from the person with an NTD and his or her parents and siblings, if possible. In families with more than one member with an NTD, it is ideal to collect blood samples from all the members with the NTD, their parents, their siblings, and any connecting relatives between the two branches.

If your family is interested in learning more about this NTD research or in participating, please contact us toll free at (866) DUKE-NTD (866) 385-3683 or e-mail ntd@chg.duhs.duke.edu.

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Additional NTD Information

NTD Research Newsletter

News About NTD Research, Summer 2006
News About NTD Research, Winter 2004

NTD Study Introduction

To obtain a print copy through the mail please call 1-(866) DUKE-NTD (866)385-3683, or e-mail ntd@chg.duhs.duke.edu to receive a copy.

CHG NTD research information contact:
Debbie Siegel
NTD Study Coordinator
Phone: (toll free)(866) DUKE-NTD (1-866-385-3683)
Phone: (919) 684-0767
E-mail: ntd@chg.duhs.duke.edu


NTD Support Groups and Information Sources

Spina Bifida Association of America (SBAA)
4590 MacArthur Blvd, NW Suite 250
Washington, DC 20007-4226
Phone:(202) 944-3285
Phone:(800) 621-3145
Fax: (202) 944-3295

Spina Bifida and Hydrocephalus Association of Canada (SBHAC)
220-388 Donald Street
Winnipeg, Manitoba R3B 2J4
Phone:(204) 925-3650
Phone:(800) 656-9488
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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