Spina bifida is a developmental complication that occurs when the brain, spinal cord, and/ or the protective covering around them do not fully develop during early pregnancy. The symptoms of spina bifida can vary greatly, depending on the area and degree to which the brain and/or spine is affected. While nearly all children with spina bifida experience some form of physical disabilities, cognitive impairments are quite rare. A child with spina bifida may experience these symptoms:

• Unusual nerve sensations
• Partial or complete paralysis
• A compressed spinal cord
• Difficulties eating or swallowing
• Difficulties controlling breathing
• Stiffness or weakness in the upper arms
• Allergies
• Skin conditions
• Gastrointestinal conditions
• Depression, as the child gets older and copes with the other symptoms

Spina bifida is the most commonly occurring neural tube defect in the United States, effecting approximately one in every 20,000 babies. Spina bifida is typically diagnosed through routine ultrasounds and screenings during pregnancy, although some mild cases may go unnoticed until the baby is born, and extremely mild cases may go completely undetected. There is no cure for spina bifida, although some kinds of corrective surgery may improve more severe symptoms. In some cases, bladder or bowel interventions or management strategies may be necessary. Physical and occupational therapy from an early age can help with mobility development, and some children with spina bifida may require assistive devices, including braces, crutches, walkers, or wheelchairs. Children with spina bifida can lead active intellectual, personal, and physical lives, especially with the support of early intervention services.

There are four types of spina bifida: occulta, closed neural tube defects, meningocele, and myelomeningocele. The symptoms of spina bifida vary from person to person, depending on the type and level of involvement.

• Occulta is the mildest and most common form in which one or more bones of the spinal column (called vertebrae) are malformed. The name “occulta,” which means “hidden,” indicates that a layer of skin covers the opening in the bones of the spine. It is often found by accident on an x-ray or similar test. This form of spina bifida very rarely causes disabilities or symptoms.
• Closed neural tube defects are a diverse group of defects in which the spine may have malformations of fat, bone, or the membranes (called the meninges) that cover the spinal cord. Many of these neural tube defects require surgery in childhood. People with this type of spina bifida may have weakness of the legs and trouble with bowel and bladder control. These issues may change or progress as children grow. It is important to have close follow-up with doctors to minimize these changes as much as possible.
• Meningocele occurs when a sac of spinal fluid pokes through the spine. This fluid is normally only around the brain and spine, but a problem with the bony covering over the spine allows it to poke out in this case. The malformation contains no nerves and may or may not be covered by a layer of skin. Individuals with meningocele may have minor symptoms.
• Myelomeningocele is the most severe form of spina bifida. A portion of the spinal cord or nerves is exposed in a sac through an opening in the spine that may or may not be covered by the meninges. The opening can be closed by surgeons while the baby is in utero or shortly after the baby is born. Most people with myelomeningocele have changes in their brain structure, leg weakness, and bladder and bowel dysfunction. Myelomeningocele is often called a snowflake condition because no two people with the condition are the same. Typically, the lower in the spine the opening occurs relates to less symptoms in the person. People with myelomeningocele require close follow-up with physicians throughout their childhood and lifespan to maximize their function and prevent complications such as kidney failure.

Spina bifida is a complex condition that is likely caused by the interaction of multiple genetic and environmental factors. Some of these factors have been identified, but many remain unknown.

Changes in dozens of genes in individuals with spina bifida and in those of their mothers may influence the risk of developing this type of neural tube defect. The best-studied of these genes is MTHFR, which provides instructions for making a protein that is involved in processing the vitamin folate (also called vitamin B9). A shortage (deficiency) of this vitamin is an established risk factor for neural tube defects like spina bifida. Changes in other genes related to folate processing and genes involved in the development of the neural tube have also been studied as potential risk factors for spina bifida. However, none of these genes appears to play a major role in causing the condition.

Researchers have also examined environmental factors that could contribute to the risk of spina bifida. As mentioned above, folate deficiency appears to play a significant role. Studies have shown that women who take supplements containing folic acid (the synthetic form of folate) before they get pregnant and very early in their pregnancy are significantly less likely to have a baby with spina bifida or a related neural tube defect. Other possible maternal risk factors for spina bifida include diabetes mellitus, obesity, exposure to high heat (such as a fever or use of a hot tub or sauna) in early pregnancy, and the use of certain anti-seizure medications during pregnancy. However, it is unclear how these factors may influence the risk of spina bifida.

Normal Function

The MTHFR gene provides instructions for making an enzyme called methylenetetrahydrofolate reductase. This enzyme plays a role in processing amino acids, the building blocks of proteins. Methylenetetrahydrofolate reductase is important for a chemical reaction involving the vitamin folate (also called vitamin B9). Specifically, this enzyme converts a form of folate called 5,10-methylenetetrahydrofolate to a different form of folate called 5-methyltetrahydrofolate. This is the primary form of folate found in blood, and is necessary for the multistep process that converts the amino acid homocysteine to another amino acid, methionine. The body uses methionine to make proteins and other important compounds.

Health Conditions Related to Genetic Changes

Homocystinuria

At least 40 mutations in the MTHFR gene have been identified in people with homocystinuria, a disorder in which the body is unable to process homocysteine and methionine properly. People with this condition often develop eye problems, abnormal blood clotting, skeletal abnormalities, and learning problems. Most of the mutations that cause homocystinuria change single amino acids in methylenetetrahydrofolate reductase. These changes impair the function of the enzyme, and some cause the enzyme to be turned off (inactivated). Other mutations lead to the production of an abnormally small, nonfunctional version of the enzyme. Without functional methylenetetrahydrofolate reductase, homocysteine cannot be converted to methionine. As a result, homocysteine builds up in the bloodstream, and the amount of methionine is reduced. Some of the excess homocysteine is excreted in urine (homocystinuria). Researchers have not determined how altered levels of homocysteine and methionine lead to the various health problems affecting multiple parts of the body in people with homocystinuria.

Age-related hearing loss

MedlinePlus Genetics provides information about Age-related hearing loss

Alopecia areata

MedlinePlus Genetics provides information about Alopecia areata

Anencephaly

Some studies have found that variations (polymorphisms) in the MTHFR gene have been associated with a small increased risk of neural tube defects, a group of birth defects that occur during the development of the brain and spinal cord. Anencephaly is one of the most common types of neural tube defect. Affected individuals are missing large parts of the brain and have missing or incompletely formed skull bones.

The most well-studied MTHFR polymorphism changes a single DNA building block (nucleotide) in the MTHFR gene. Specifically, it replaces the nucleotide cytosine with the nucleotide thymine at position 677 (written as 677C>T). This common variant results in a form of methylenetetrahydrofolate reductase that has reduced activity at higher temperatures (the enzyme is thermolabile). People with the 677C>T polymorphism, particularly those with the genetic change in both copies of the gene, have elevated levels of homocysteine in their blood (hyperhomocysteinemia) resulting from the reduced activity of methylenetetrahydrofolate reductase.

Researchers have studied MTHFR gene polymorphisms and hyperhomocysteinemia in individuals with neural tube defects and in their mothers, but it remains unclear how these variations affect the developing brain and spinal cord. The association with neural tube defects may be related to differences in the ability of methylenetetrahydrofolate reductase to process folate. While a shortage (deficiency) of this vitamin is an established risk factor for neural tube defects, there are many factors that can contribute to folate deficiency.

MTHFR gene polymorphisms are common worldwide, with an estimated 25 percent of Hispanics and 10 to 15 percent of North American whites having the 677C>T polymorphism in both copies of the gene. Most people with MTHFR gene polymorphisms do not have neural tube defects, and their children are also typically unaffected.

Spina bifida

Some studies have found that polymorphisms in the MTHFR gene are also associated with a small increased risk of spina bifida, another common type of neural tube defect. When the spine forms in people with this condition, the bones of the spinal column do not close completely around the developing nerves of the spinal cord. As a result, part of the spinal cord may stick out through an opening in the spine, leading to permanent nerve damage.

As described above, variations in the MTHFR gene generally result in hyperhomocysteinemia due to reduce activity of methylenetetrahydrofolate reductase and its ability to process folate. It is unclear how MTHFR gene changes might influence the development of neural tube defects. However, these variations are common in many populations worldwide. Most people with MTHFR gene polymorphisms do not have neural tube defects, nor do their children.

Other disorders

Polymorphisms in the MTHFR gene can alter or decrease the activity of methylenetetrahydrofolate reductase, leading to a mild increase of homocysteine in the blood (hyperhomocysteinemia). The two MTHFR gene polymorphisms that are the most common and the most frequently studied are 677C>T and a change that replaces the nucleotide adenosine with the nucleotide cytosine at position 1298 (written as 1298A>C).

An increase in homocysteine levels caused by MTHFR gene polymorphisms have been studied as possible risk factors for a variety of common conditions. These include high blood pressure (hypertension), blood clots, pregnancy loss, psychiatric disorders, and certain types of cancer. Research indicates that individuals who have the 677C>T polymorphism on both copies of the MTHFR gene have an increased risk of developing vascular disease, including heart disease and stroke. The 677C>T polymorphism has also been suggested as a risk factor for cleft lip and palate, a birth defect in which there is a split in the upper lip and an opening in the roof of the mouth.

Studies of MTHFR gene variations in people with these disorders have had mixed results, with associations found in some studies but not in others. Therefore, the role that changes in the MTHFR gene play in these disorders remains unclear. It is likely that additional factors influence the processing of homocysteine and that variations in homocysteine levels play a role in whether a person develops any of these conditions. A large number of genetic and environmental factors, most of which remain unknown, likely determine the risk of developing most common complex conditions.

Other Names for This Gene

• 5,10-methylenetetrahydrofolate reductase
• 5,10-methylenetetrahydrofolate reductase (NADPH)
• methylenetetrahydrofolate reductase (NAD(P)H)
• MTHR_HUMAN

Genomic Location

Most cases of spina bifida are sporadic, which means they occur in people with no history of the disorder in their family. A small percentage of cases have been reported to run in families; however, the condition does not have a clear pattern of inheritance. First-degree relatives (such as siblings and children) of people with spina bifida have an increased risk of the condition compared with people in the general population.

About 1,500 infants are born with spina bifida each year in the United States.

Anyone can give birth to an infant with spina bifida. However, parents who already have had a child with spina bifida or another neural tube defect have a 4% increased risk of having a second child with spina bifida. Parents of two children with spina bifida have about a 10% chance of having another child with this condition. When one parent has spina bifida, there is about a 4% chance that his or her child also will have it.

Women who are obese, have poorly controlled diabetes, or take certain antiseizure medications are at greater risk of having a child with spina bifida.

In most cases, spina bifida is diagnosed before birth (prenatal). However, some mild cases may go unnoticed until after birth (postnatal). Very mild forms of spinal bifida are found when doing tests for other conditions or may never be detected.

Prenatal Diagnosis

The most common screening methods used to look for spina bifida during pregnancy are maternal serum alpha fetoprotein (MSAFP) screening and fetal ultrasound. A doctor can also perform an amniocentesis test.

• Maternal serum alpha fetoprotein (MSAFP) screen. At 16 to 18 weeks of pregnancy, a sample of the mother’s blood is taken to measure the level of a protein called alpha-fetoprotein (AFP), which is made naturally by the fetus and placenta. During pregnancy, a small amount of AFP normally crosses the placenta and enters the mother’s bloodstream. Abnormally high levels of AFP may indicate that the fetus has spina bifida or other neural tube defect. This test is not specific for spina bifida and cannot definitively determine that there is a problem with the fetus. This means that a high AFP level alone is not enough to be sure the fetus has a neural tube defect. If a high level of AFP is detected, the doctor may request additional testing, such as an ultrasound or amniocentesis.

The second trimester MSAFP screen may be performed alone or as part of a larger, multiple-marker screen. Multiple-marker screens can look for neural tube defects and other birth defects, including Down syndrome and other chromosomal abnormalities. First trimester screens for chromosomal abnormalities also exist but signs of spina bifida are not evident until the second trimester when the MSAFP screening is performed.

• Ultrasound. A fetal ultrasound uses high-frequency sound waves to create a picture of the developing baby inside the womb. It is highly accurate in diagnosing some birth defects during pregnancy, including spina bifida. Fetal ultrasound can be performed during the first trimester (usually between 11-14 weeks) and the second trimester (usually at 18-22 weeks), and diagnosis is more accurate during the second trimester.
• Amniocentesis. In this test, a doctor removes a sample of the amniotic fluid that surrounds the fetus and tests it for protein levels that may indicate a neural tube defect and genetic disorders.

Postnatal Diagnosis

Closed neural tube defects are often recognized at birth due to an abnormal fatty mass, tuft or clump of hair, or a small dimple or birthmark on the skin at the site of the spinal malformation. Spina bifida occulta is usually found when x-rays are done for another reason.

In rare cases, myelomeningocele and meningocele are not diagnosed during routine prenatal tests. The baby will be diagnosed when they are born with a bubble on their back. Babies with myelomeningocele and closed neural tube defects may have muscle weakness in their feet, hips, and legs that result in joint deformities first noticed at birth. Mild cases of spina bifida (occulta, closed neural tube defects) not diagnosed during prenatal testing may be detected postnatally using ultrasound or X-ray imaging to look at the spine.

Doctors may use magnetic resonance imaging (MRI) or a computed tomography (CT) scan to get a clearer view of the spinal cord and vertebrae. To evaluate for hydrocephalus, the doctor will request a head ultrasound, CT or MRI to look for extra cerebrospinal fluid inside the brain.

Treatment for spina bifida typically involves surgery to repair the opening in the spine. Surgery can be done before or shortly after birth. Surgery before birth (fetal surgery) is an option depending on the severity of the spina bifida and the health of the mother. While surgery may prevent symptoms from getting worse, it cannot correct any damage to the spinal cord of nerves that is already present. Mild cases of spina bifida may not require treatment.

Other treatment options are focused on managing the long-term symptoms and may include a ventriculoperitoneal shunt to drain fluid from the head, antibiotics as protection from infection, and physical therapy.

Specialists involved in the care of someone with spina bifida may include:

• Neurologist
• Neurosurgeon
• Fetal surgeon
• Urologist
• Orthopedist
• Dermatologist
• Physical therapist

No two people with spina bifida are exactly alike. Health issues and treatments for people with spina bifida will be different for each person. Some people have issues that are more severe than other people. Those born with “open” spina bifida usually have more health issues and need more types of treatments.

Some health issues and treatments related to spina bifida include the following:

Open Spina Bifida

Sometimes when a baby has open spina bifida, or myelomeningocele, doctors will perform surgery to close the spine before the baby is born.

This surgery is a major procedure for the mother and the baby, and may not be available where you live. Contact a doctor who works regularly with spina bifida babies and expectant mothers about the pros and cons of this option.

Hydrocephalus

Many babies born with spina bifida get hydrocephalus (often called water on the brain). This means that there is extra fluid in and around the brain. The extra fluid can cause the spaces in the brain, called ventricles, to become too large and the head can swell. Hydrocephalus needs to be followed closely and treated properly to prevent brain injury.

If a baby with spina bifida has hydrocephalus, a surgeon can put in a shunt. A shunt is a small hollow tube that will help drain the fluid from the baby’s brain and protect it from too much pressure. Additional surgery might be needed to change the shunt as the child grows up or if it becomes clogged or infected.

Tethered Spinal Cord

Many people with open spina bifida have tethered spinal cords. Normally, the bottom of the spinal cord floats around freely in the spinal canal. A tethered spinal cord is attached to the spinal canal. When this happens, the spinal cord stretches as a person grows, which can permanently damage the spinal nerves. The person might have back pain, scoliosis (crooked spine), leg and foot weakness, changes in bladder or bowel control, and other problems. A tethered spinal cord can be treated with surgery.

Mobility and Physical Activity

People affected by spina bifida get around in different ways. These include walking without any aids or assistance; walking with braces, crutches or walkers; and using wheelchairs.

People with spina bifida higher on the spine (near the head) might have paralyzed legs and use wheelchairs. Those with spina bifida lower on the spine (near the hips) might have more use of their legs and use crutches, braces, or walkers, or they might be able to walk without these devices.

Regular physical activity is important for all people, but especially for those with conditions that affect movement, such as spina bifida. CDC recommends 60 minutes of physical activity a day. There are many ways for people with spina bifida to be active. For example, they can:

• Engage in active play with friends.
• Roll or walk in the neighborhood.
• Participate in community programs, such as the Early Intervention Program for Infants and Toddlers with Disabilities and Special Education Services for Preschoolers with Disabilities, which are free programs in many communities.
• Enjoy parks and recreation areas with playgrounds that are accessible to people with disabilities.
• Do exercises recommended by a physical therapist.
• Attend summer camps and recreational facilities that are accessible for those with disabilities.
• Participate in sports activities (for example, swimming) and teams for people with or those without disabilities.

Using the Bathroom

People with spina bifida often cannot control when they go to the bathroom (incontinence). They also can develop urinary tract infections. It is important to develop a plan for going to the bathroom that works and is as simple as possible. This can lead to increased health, participation, and independence, and avoid embarrassment for people with spina bifida. Healthcare providers can help develop a plan for each person. A tube (catheter) inserted in the bladder can help drain urine. In some cases, extra fiber can be added to the diet to keep bowel movements regular. Surgery also might be recommended.

Skin Care

Children and adults living with spina bifida may have limited feeling in some areas of their body, leaving them unable to feel cuts, bruises, sores, and dry skin. Since a person with spina bifida may not know they have been hurt, they may be unable to tell a parent or caregiver that they need help.

Pressure sores occur when there is prolonged pressure on soft tissue, skin, and muscle. Healthcare professionals report skin wounds as one of the primary diagnoses associated with the hospitalization of people with spina bifida. Pressure sores can lead to infection, amputation, or even death.

By checking skin regularly for redness including under braces, people with spina bifida, along with their parents and caregivers, can identify skin problems before they become pressure sores.

Additional ways to protect the skin:

• Avoid hot bath water, heaters, hot dishes, hot car seats, and metal seatbelt clasps, since they may cause burns.
• Make sure you are wearing properly fitting shoes at all times, even when swimming.
• Use sunscreen, and don’t stay out in the sun too long.
• Do not sit or lie in one position for too long.

Latex (Natural Rubber) Allergy

Many people with spina bifida are allergic to products that contain latex, or natural rubber. This means they should not use items made of natural rubber. For babies, this would include rubber nipples and pacifiers. A person with this type of allergy can wear a bracelet to alert other people of the allergy.

Health Checks

Every person needs a primary care provider, such as a pediatrician, nurse practitioner, general family doctor, or internist. The primary care provider will want to make sure that he or she is healthy; developing normally; and receiving immunization against diseases and infections, including the flu.

In addition to seeing a primary health care provider, a person with spina bifida will be checked and treated as needed by doctors who specialize in different parts of the body. These doctors might suggest treatments or surgeries to help the person.

These specialists might include:

• An orthopedist, who will work with muscles and bones.
• A urologist, who will check the kidneys and bladder.
• A neurosurgeon, who will check the brain and spine.

Other Concerns

Some people with spina bifida have difficulty with:

• Learning
• Relating to others
• Vision
• Staying at a healthy weight
• Depression

Folic acid, also called folate, is an important vitamin for the development of a healthy fetus. Although taking this vitamin cannot guarantee having a healthy baby, it can help. Studies show that women of childbearing age who add folic acid to their diets can significantly reduce the risk of having a child with a neural tube defect. Therefore, it is recommended that all women of childbearing age take a daily vitamin supplement with 400 micrograms of folic acid before and during early pregnancy.

Foods high in folic acid include dark green vegetables, egg yolks, and some fruits. Many foods—such as some breakfast cereals, enriched breads, flours, pastas, rice, and other grain products—are now fortified with folic acid. Many multivitamins contain the recommended dosage of folic acid as well.

Women who already have a child with spina bifida, who have spina bifida themselves, or who have already had a pregnancy affected by any neural tube defect are at greater risk of having another child with a neural tube defect. These women should take a higher prescription dose of folic acid before and early in pregnancy.