Top Guide on Genetic Causes of Spina Bifida (FAQ)

Spina bifida (SB) is overwhelmingly difficult to understand when it comes to the causes because even now, medical experts are still quite unsure as to the exact reason one is born with this condition. There are many suspected causes, including hereditary and genetic links.

Often, one of the questions family members of the patient with spina bifida will ask “Why us?” “What is the cause of my condition?” “Is my condition genetic and can I pass it on if I have children?”

These are all valid and understandable questions that we will attempt to answer in this article by looking at the possible familial connections of SB.

Does Spina Bifida Come from Mom or Dad?

Spina bifida may come from mom or dad; however, it does not have a clear pattern of inheritance, so there is no way to be one hundred percent sure of this. A woman with SB has about a 1 – 5% chance of having a Spina Bifida child, which increases to 15% if both parents have SB. This is clearly a more complex condition than one that is directly passed down from the parents, yet a few cases have been reported to run in families [1].

Nonetheless, it is still quite possible that siblings, children, and other first-degree relatives of people with spina bifida may be more likely to develop SB compared with people in the general population. The majority of reported SB cases have been sporadic. Therefore, the people diagnosed with the condition have no history of the disorder being in their family [2].

Dr. Margo Whiteford on Spina Bifida and Genetics

Can Spina Bifida Run in Families?

Yes, SB can run in families. If you or a close relative is diagnosed with the condition, your child may likely be born with it; but the chances of that happening is very low.

Additionally, having more than one child with the condition is possible since your chances of having other children with the condition are increased if your previous child has spina bifida. It is believed that first-born babies are at higher risk. Other neural tube congenital disabilities within the family’s history can also predispose a child to being born with SB [3].

How is Spina Bifida Passed On?

Scientists and other medical experts are unsure of how spina bifida gets passed on; however, they have some theories. As SB is a form of neural tube defect, it is thought to result from folate deficiency in combination with genetics and other environmental factors, like the mother’s exposure to toxins during pregnancy.

Essentially, neural tube defects are caused by genes passed on from both parents; therefore, if SB is hereditary, then it is fair to assume that it would be passed on in this manner [4].

Is Spina Bifida a Dominant or Recessive Trait?

Spina Bifida is not usually a single dominant or recessive trait. According to a scientific report, since SB is such a complex condition, its risk varies by ethnic group, socioeconomic group, and time. In this report, they found that the likelihood of a group of offspring having the same two parents to be born with SB approximates to 1 in 1000 births [5].

Further, experts have collected evidence suggesting SB development is controlled by a limited number of genes (oligogenic inheritance pattern), as opposed to being a model based on single dominant or recessive genes [6].

Bottom line, it is highly unlikely that SB is either a dominant or recessive trait.

What Gene is Responsible for Spina Bifida?

A number of genes have been linked to the development of Spina Bifida.The gene MTHFR also seems to be involved in at least some of the spina bifida cases. MTHFR is a gene that codes for a protein essential in folic acid (vitamin B9) metabolism. MTHFR in infants is associated with approximately a 70% increased risk for the development of SB.

Another folate-related gene, SHMT1, is altered in some patients [1].

The scientists based at UCL Great Ormond Street Institute of Child Health identified mutations in a gene that contains information needed to create spinal cord tissue; the gene Vangl2 was present in 16% of developing spinal cord cells of mouse embryos.

They determined that this mutation was enough to produce spina bifida [7].

Who is Most at Risk for Spina Bifida?

Any child can be born with spina bifida; however, the children more at risk for SB are usually:

• those with a family history of SB or another neural tube birth defect
• children with folic acid deficiency
• those born to teen mothers have a higher risk of SB
• children born to a mother with a history of miscarriage
• the first-born babies are at higher risk
• children born to a mother with diabetes, especially if it is out of control during pregnancy
• those with maternal obesity. Researchers have established that there is a link between pre-pregnancy obesity and SB, along with other neural tube birth defects
• children whose mothers were exposed to harmful chemicals during pregnancy
• and children of lower socioeconomic status are at higher risk for spina bifida. Medical experts believe this to be linked to poor diet [4].

These are not concretely confirmed, but risk factors that have been identified from them being present in a number of cases. As earlier mentioned, SB is considerably complex and does not seem to be caused by one single factor.

Is Spina Bifida Genetic or Hereditary?

Spina bifida is both genetic and hereditary. In fact, scientists believe this condition to be caused by a combination of genetic, hereditary, and environmental factors. As such, pinpointing a precise cause is quite challenging.

While some cases may have strong evidence of being related to the inheritance of specific genetic changes, chromosome abnormalities, or fetal exposure to teratogens, others are simply a mystery [8].

Is Spina Bifida Genetic or Chromosomal?

Spina bifida is not singularly genetic or chromosomal. This condition is a result of several factors affecting the development of the spinal cord.

In addition, changes in several genes in individuals with SB and their mothers can increase the chances of a child being born with the condition. The most commonly highlighted gene is the MTHFR gene, which is located on the short arm of chromosome 1. The MTHFR gene encodes an enzyme called methylenetetrahydrofolate reductase.

This enzyme has a vital role in amino acid processing with folic acid [9].

When this gene is defective or has mutated, it increases the likelihood of a spina bifida diagnosis.

A study that looked at chromosomal abnormalities in fetuses with open neural tube defects determined that a high number of fetuses with open NTD are chromosomally abnormal. It further stated that an underlying chromosomal abnormality was diagnosed in 10 fetuses (7%), six with SB, but additional investigations evidenced associated anomalies [10].

What are the Chances of a Baby having Spina Bifida?

Newborn Baby with Spina Bifida Undergoes Multiple Surgeries Video

According to the American Pregnancy Association, spina bifida occurs in approximately 7 out of every 10,000 live births in the United States, which means any baby can be born with SB. Additionally, the Spina Bifida Association of America purports that more than 166,000 people in the United States are living with this birth defect.

SB affects more than 1,500 pregnancies each year; however, this figure is steadily decreasing [10].

What Group is at the Highest Risk for Spina Bifida Babies?

The group at highest risk of having spina bifida babies include:

• parents with a family history of SB or another neural tube birth defect
• a lack of folic acid during pregnancy
• teen mothers
• mothers with a history of miscarriage
• mothers with diabetes, especially if it is out of control during pregnancy
• mothers with obesity. Researchers have established that there is a link between pre-pregnancy obesity and SB, along with other neural tube birth defects
• mothers exposed to harmful chemicals during pregnancy
• mothers of lower socioeconomic status are at higher risk for SB. Medical experts believe this to be linked to poor diet [4].

These are not concretely confirmed, but risk factors that have been identified from them being present in a number of cases.

How Accurate is Blood Test for Spina Bifida?

A blood test that checks alpha-fetoprotein (AFP) levels, which may indicate spina bifida, has proven to be 80 percent accurate. Alpha-fetoprotein levels that are higher than normal are usually indicative of a neural tube defect [12].

(Video of Dr Gabriel Galea from the Institute of Child Health talking about the Genetic causes of Spina Bifida)

Is Spina Bifida more Common in Males or Females?

According to the Center for Disease Control, spina bifida is more common among females than males in most populations. Factors that the organization has outlined as possible causes for these sex-specific variations are:

• the rate of development of female and male embryos
• susceptibility to teratogenic insult
• differential rates of spontaneous abortion for male and female fetuses (more males were aborted than females due to early detection of the birth defect) [13].

How Soon can you Tell if your Baby has Spina Bifida?

You can tell that your baby has spina bifida as early as the first trimester (11 to 14 weeks).

An ultrasound is typically performed during this time, and it is also the most accurate method to detect SB while in uterine. For a more accurate diagnosis during pregnancy, it is best to check for developmental abnormalities during the second trimester (18 to 22 weeks), again using an ultrasound to detect Spina Bifida. Or an advanced ultrasound can be done by a specialist who will be able to interpret the results more accurately than an OBGYN.

For this reason, it is essential for expectant mothers to have prenatal care and keep every appointment [14].

SB is a complex condition that cannot be associated with only one causative factor. As such, medical experts, though still not clear on how the condition is caused, have linked it to a combination of several potential factors.

Hereditary, genetics, and environmental contributors all play a role in a child being born with spina bifida.

Video of Dr. Margo Whiteford (pediatrician and geneticists ) talks about the hereditary factor of Spina Bifida.

 

References

1. Is Spina Bifida Linked to Hereditary and Genetics? (2022). Spina Bifida Resource Center. https://www.spinabifida.net/causes/hereditary-and-genetics/
2. Spina bifida: MedlinePlus Genetics. (2013). Medlineplus.gov. https://medlineplus.gov/genetics/condition/spina-bifida/#inheritance
3. NHS Choices. (2022). Causes – Spina bifida. https://www.nhs.uk/conditions/spina-bifida/causes/
4. default – Stanford Children’s Health. (2019). Stanfordchildrens.org. https://www.stanfordchildrens.org/en/topic/default?id=spina-bifida-90-P02415
5. Juriloff, D. M. (2000). Mouse models for neural tube closure defects. Human Molecular Genetics, 9(6), 993–1000. https://doi.org/10.1093/hmg/9.6.993
6. Copp, A. J., & Greene, N. D. (2010). Genetics and development of neural tube defects. The Journal of pathology, 220(2), 217–230. https://doi.org/10.1002/path.2643
7. UCL. (2021, February 19). Spina bifida can be caused by uninherited genetic mutations. UCL News. https://www.ucl.ac.uk/news/2021/feb/spina-bifida-can-be-caused-uninherited-genetic-mutations
8. Spina bifida – About the Disease – Genetic and Rare Diseases Information Center. (2021). Nih.gov. https://rarediseases.info.nih.gov/diseases/7673/spina-bifida
9. Super User. (2022). Genetic Testing – Spina bifida (spina bifida) – Gen MTHFR. – IVAMI. Ivami.com. https://www.ivami.com/en/genetic-testing-human-gene-mutations-diseases-neoplasias-and-pharmacogenetics/4414-genetic-testing-spina-bifida-spina-bifida-gen-mthfr
10. Sepulveda, W., Corral, E., Ayala, C., Be, C., Gutierrez, J., & Vasquez, P. (2004). Chromosomal abnormalities in fetuses with open neural tube defects: prenatal identification with ultrasound. Ultrasound in Obstetrics and Gynecology, 23(4), 352–356. https://doi.org/10.1002/uog.964
11. Spina Bifida Test. (2021, April 26). American Pregnancy Association. https://americanpregnancy.org/healthy-pregnancy/birth-defects/spina-bifida/
12. Neural Tube Defect Screening – Penn Medicine. (2022). Pennmedicine.org. https://www.pennmedicine.org/for-patients-and-visitors/find-a-program-or-service/obstetrics/prenatal-genetic-testing/diagnosis-and-screening-services/neural-tube-defect-screening
13. Prevalence of Spina Bifida at Birth — United States, 1983-1990: a Comparison of Two Surveillance Systems. (2022). https://www.cdc.gov/mmwr/preview/mmwrhtml/00040954.htm
14. Spina bifida – Diagnosis and treatment – Mayo Clinic. (2022). Mayoclinic.org; https://www.mayoclinic.org/diseases-conditions/spina-bifida/diagnosis-treatment/drc-20377865

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