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Scientists Search For Spina Bifida Genes
by RONDA WENDLER
Shriners Hospital for Children
The search to identify the genes associated with spina bifida is being fueled by a $288,000, three-year grant from Shriners Hospital's National Headquarters in Tampa, Fla. Dr. Hope Northrup, who holds a research appointment at Shriners Hospital for Children in Houston and also serves as an associate professor of pediatrics and medical genetics division director at The University of Texas-Houston Medical School, has received the grant to fund her project titled, "Neural Tube Defects: Epidemiologic and Genetics Factors."
Dr. Hope Northrup (right) works with graduate student Kelly Volcik to identify genes that cause spina bifida.
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While researchers are uncertain why spina bifida occurs, current studies suggest that 60 percent of cases are genetic, while 40 percent are caused by environmental factors, Dr. Northrup says.
The search for spina bifida-causing genes is complicated, she explains, because of the lack of clear-cut inheritance in spina bifida, the scarcity of multigenerational spina bifida families, and the uncertainty about how genetics and environmental factors work together in causing spina bifida.
To overcome these obstacles, she and other researchers contributing to the project identified 500 families affected by spina bifida - a large study sample by typical research standards.
The families, which are recruited from Shriners Hospitals in Houston, Los Angeles and Lexington, will all be tested for genetic associations to determine whether "suspicious" genes tend to occur repeatedly among families. Such an occurrence would be cause for further investigation of the genes in question, Dr. Northrup says.
Seventy genes from five categories will be tested for genetic association to spina bifida. The five categories of candidate genes include: genes involved in folate and glucose metabolism (folate because folate has been shown to play a part in reducing neural tube defects and glucose because studies show that obese women are more likely to have babies with neural tube defects); genes that have been shown to cause neural tube defects in rats and mice; HOX and PAX genes, which play an important role in establishing body symmetry; growth factor and growth factor receptor genes; and proto-oncogenes, which, in addition to causing cancer, also may contribute to physical development.
The study population includes two ethnic groups - Caucasians from North America and Hispanics of Mexican descent. The Caucasian population is drawn from Shriners Hospital for Children in Lexington, Ky., and includes families from Appalachia - the geographic region with the greatest number of Caucasians affected by spina bifida in the United States. The Hispanic, Mexican descent population is from the Houston and Los Angeles hospitals. Mexico has one of the highest rates of neural tube defects in the world, and among ethnic groups in the United States, Hispanics have the highest rate of neural tube defects.
The data generated from these families will be analyzed by ethnicity and by level of defect (the location along the spine where malformation occurred).
In asthma, different genes have been shown to be responsible in different ethnic groups. The same may be true in spina bifida, Dr. Northrup says. In addition, it may be found that different levels of defect in spina bifida are caused by different genes.
"For these reasons, it is important to examine the data in multiple ways," Dr. Northrup explains.
"Understanding the underlying basis of neural tube disorders is the first step toward preventing and treating this devastating birth defect," she states.
To increase awareness of spina bifida to those in the education field, The Houston Chapter of the National Spina Bifida Association is offering a new outreach/ public awareness program called Project Spina Bifida. This presentation informs school districts, teachers and those in an education-related field about spina bifida and emphasizes the special learning needs of children with spina bifida. To arrange for teachers, schools or school districts to be contacted about this program, call Jo Ann Evans, president of the Spina Bifida Association-Texas Gulf Coast, at 409-849-6864.
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Spina bifida occulta, or "hidden" spina bifida, occurs when there is a small defect or gap in a few of the vertebrae in the backbone. The spinal cord and nerves are usually normal, and most affected individuals have no problems caused by this minor abnormality. Many individuals live out their lives without ever realizing they have the condition. Signs to watch for include:
- Decreased sensation in feet or legs
- Frequent urinary tract infections
- Clubbed foot or foot deformities
- Hairy patch at the base of the spine
- Scoliosis (curvature of the spine)
- A skin depression or dimple on the lower back
- Areas of increased pigmentation
- A fatty lump under the skin
- Reoccurring back pain
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What to Expect
While spina bifida remains one of the most complex of all birth defects, understanding of the condition is constantly and rapidly evolving.
"Traditionally, almost all children born with spina bifida died in infancy or early childhood from infection or the complications of hydrocephalus," Dr. Haynes says. "However, the advent of antibiotics and advanced surgical techniques have made it possible for individuals with spina bifida to achieve longer lives and increased independence," he explains.
Treated aggressively, most children survive. Four out of five reach their first birthday, and three out of five reach their 16th. Because neurologic and musculoskeletal deterioration often increase as patients grow older, regular medical followup is important. However, the complexities of treatment often seem overwhelming to the parents, the patient, and sometimes to the physician since so many organ systems are involved, says Dr. Haynes.
"A multidisciplinary team approach utilizing the expertise of urologists, orthopedists, neurosurgeons and physical therapists is essential throughout these patients' lives if they are going to participate meaningfully in society," he states.
The knowledge level about spina bifida is rapidly expanding, he added, giving new hope to patients and their families.
"Over the past half-decade, we have seen significant improvement, not only in the rate of survival, but also in the outlook for these individuals," Dr. Haynes says. "It is our hope that the future is equally as bright, and that the majority of people with spina bifida can participate in society in a meaningful way."
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What Causes Spina Bifida?
Spina bifida - a condition in which the spinal cord and spinal column, or backbone, fail to develop normally - occurs in one out of every thousand children born in the United States, and is more prevalent in females than males, and less prevalent in blacks and Asians than Hispanics and whites. Researchers attribute the cause to both genetic and environmental factors. A woman who has given birth to a child with spina bifida has a one in 40 chance of having a second child with the condition, says Dr. Richard Haynes, chief of staff at Shriners Hospital for Children.
"This statistic supports the belief that spina bifida tends to occur in families, although it does not appear to be attributed to a single gene. Genetic researchers may find there is a genetic and a nongenetic form of spina bifida, but further analysis will be required to determine this," he states.
For reasons that no one yet understands, spina bifida for years has been more prevalent in Ireland than anywhere else in the world. At one time, it was thought that blighted potatoes might contain a substance causing spina bifida, but experiments in which potatoes were entirely avoided proved this theory false. Although women in the study refrained from eating potatoes, they still had a higher than normal incidence of babies born with spina bifida - five times greater than anywhere else in the world. Recently, China has begun experiencing the same phenomenon, although traditionally spina bifida has not been prevalent in the Asian population.
Today, a deficiency in folic acid intake in a soon-to-be-pregnant woman prior to conception is believed to be a major cause of spina bifida. Folic acid, or folate, is a common B vitamin found in foods such as cereals, broccoli, spinach, corn, and also as a vitamin supplement. All women of childbearing age should consume 0.4 milligrams of folic acid daily to reduce the risk of having a pregnancy affected by spina bifida.
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©2006 Texas Medical Center
E-Mail: tmc-info@tmc.edu
URL: http://www.tmc.edu/tmcnews/06_01_99/page_04.html
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