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Neural tube defects
These conditions can range in severity and affect different parts of the central nervous system. NTDs are typically diagnosed during pregnancy or shortly after birth and can lead to a variety of physical and developmental challenges.
Overview
Neural tube defects (NTDs) are a category of birth anomalies that arise from incomplete closure of the neural tube, a structure in the early developing foetus that ultimately forms the brain and spinal cord. This vital process normally occurs between the third and fourth weeks of pregnancy. When closure is incomplete, it can lead to openings in the spine, brain, or both [PMID:33653198].
There are several types of NTDs, with the most common being spina bifida and anencephaly. Spina bifida involves an opening in the spinal column, which can sometimes expose the spinal cord and nerves. Anencephaly is a more severe condition where a large part of the brain and skull do not develop, which is not compatible with long-term survival.
Symptoms & clinical features
The symptoms of neural tube defects vary significantly depending on the type and severity of the condition. For instance, spina bifida can present in different forms. Spina bifida occulta, the mildest form, often has no outward signs and may only be discovered incidentally during imaging for other reasons. A small gap in the spine bones is present, but the spinal cord and nerves are typically unaffected.
More severe forms of spina bifida, such as meningocele and myelomeningocele, involve a visible sac on the baby's back. In meningocele, the sac contains only membranes, while in myelomeningocele, it contains spinal cord tissue and nerves. These more severe types can lead to a range of issues including weakness or paralysis in the legs, bladder and bowel control problems, hydrocephalus (excess fluid in the brain), and learning difficulties [PMID:28751410]. Anencephaly results in the absence of major parts of the brain and skull, leading to a condition that is lethal shortly after birth.
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Affected organs
Neural tube defects primarily affect the central nervous system, which includes the brain and spinal cord. Depending on where the neural tube fails to close, the effects can range from subtle to severe. In spina bifida, the spinal cord and associated nerves can be damaged, leading to issues with nerve function below the level of the defect.
The brain can also be affected, particularly in cases of anencephaly where large portions of the brain do not form. In other NTDs, conditions like hydrocephalus, where cerebrospinal fluid accumulates in the brain, can lead to increased pressure and potential brain damage. The bones of the skull and spine are also directly impacted, as their formation is linked to the closure of the neural tube.
Risks & severity
The severity of neural tube defects varies widely. Spina bifida occulta often has no noticeable impact, while myelomeningocele can cause significant lifelong disabilities. Anencephaly is the most severe form and is invariably fatal. The exact prevalence of NTDs is approximately 1 in 1,000 live births in the UK, although this can vary globally and has decreased in some regions due to public health interventions [PMID:23783424].
Risks for developing NTDs are complex, involving both genetic and environmental factors. Key risk factors include insufficient folate intake before and during early pregnancy, certain medications, and a family history of NTDs. While some NTDs can be detected before birth, the specific long-term outcomes depend heavily on the type of defect, its location, and the extent of nerve involvement.
Genetic causes
Neural tube defects are typically considered polygenic and complex, meaning they arise from a combination of multiple genetic factors and environmental influences. This differs from conditions caused by a single gene change. While many genes may contribute, one gene often researched in connection with NTDs is MTHFR.
The MTHFR gene provides instructions for making an enzyme called methylenetetrahydrofolate reductase. This enzyme plays a crucial role in processing folate (vitamin B9) and methionine metabolism. Folate is essential for cell growth and development, particularly for the proper closure of the neural tube. Changes in the MTHFR gene can affect how efficiently this enzyme functions, potentially impacting folate metabolism and increasing the susceptibility to NTDs, especially when combined with other risk factors.
Inheritance pattern
Neural tube defects typically follow a polygenic/complex inheritance pattern. This means that a combination of multiple genes, along with environmental factors, contributes to their development. It is not usually inherited in a simple dominant or recessive manner, as is seen with some other genetic conditions.
While there may be a genetic predisposition, meaning that certain gene variants can increase an individual's risk, having these variants does not guarantee that an NTD will occur. Similarly, if one child in a family has an NTD, the risk for subsequent children is increased compared to the general population, but it is not 100%. Genetic counselling can help families understand these complex risks.
Diagnosis & testing
Neural tube defects are often diagnosed during pregnancy through routine prenatal screening. This can include maternal blood tests (such as alpha-fetoprotein screening) and ultrasound scans, which can visualise structural abnormalities of the foetus. If screening results suggest a potential NTD, further diagnostic tests like a detailed ultrasound or foetal MRI may be performed.
Following birth, a diagnosis is typically made by physical examination and imaging studies such as ultrasound, X-ray, CT, or MRI. Genetic testing, specifically looking at genes like MTHFR, is not usually a primary diagnostic tool for NTDs themselves, but may be considered as part of research or if other genetic conditions are suspected. In the UK, genetic testing for complex conditions like NTDs can be accessed via the NHS Genomic Medicine Service, often through an R-code, following referral from a specialist.
Management & lifestyle
Management of neural tube defects is highly individualised and depends on the specific type and severity of the condition. For severe cases like myelomeningocele, surgical intervention to close the spinal opening is often performed shortly after birth to prevent infection and further nerve damage. This surgery is typically followed by ongoing multidisciplinary care involving paediatricians, neurosurgeons, orthopaedic surgeons, urologists, and physiotherapists.
Surveillance for potential complications, such as hydrocephalus, bladder and bowel dysfunction, and mobility issues, is crucial. Regular follow-up appointments and ongoing therapies, including physiotherapy, occupational therapy, and speech therapy, may be necessary to support development and manage symptoms. Lifestyle considerations include maintaining a healthy diet and ensuring adequate folate intake, particularly for individuals who may become pregnant, to help reduce the risk of NTDs in future pregnancies.
UK care pathway
In the UK, individuals and families affected by neural tube defects are typically supported through the NHS. If an NTD is suspected or diagnosed, referral to a clinical genetics service is an important step. Genetic counsellors within these services can provide information about the condition, discuss inheritance patterns and recurrence risks, and offer support.
For diagnostic testing or further investigation, a clinician may refer for genomic testing under the NHS Genomic Medicine Service using an appropriate R-code, if specific genetic causes are suspected or for research purposes. The multidisciplinary approach to care involves specialists from various fields working together to manage the complex needs of affected individuals.
Frequently asked questions
Can neural tube defects be prevented?
While not all neural tube defects can be prevented, taking a daily folic acid supplement (400 micrograms) before conception and during the first 12 weeks of pregnancy significantly reduces the risk. Some individuals, particularly those with a family history or certain medical conditions, may be advised to take a higher dose.
What is the difference between spina bifida and anencephaly?
Spina bifida is an NTD where there is an opening or gap in the spine, which can lead to varying degrees of nerve damage and physical challenges. Anencephaly is a more severe NTD where a large part of the brain and skull does not form, which is not compatible with long-term survival.
If I have one child with an NTD, what is the risk for future pregnancies?
If you have had one child with an NTD, the risk of having another child with an NTD is increased compared to the general population. A genetic counsellor can provide a more precise risk assessment based on your family history and offer guidance on strategies to reduce this risk.
Is genetic testing available for neural tube defects?
While NTDs are often complex and involve multiple factors, genetic testing is not typically a primary diagnostic tool for the condition itself. However, research into genetic factors like MTHFR variants is ongoing. If there's a strong family history or other concerns, a referral to clinical genetics may be made to discuss potential genetic contributions.
How are neural tube defects managed after birth?
Management depends on the type and severity of the NTD. For conditions like myelomeningocele, surgery to close the defect is often performed soon after birth. This is followed by long-term, multidisciplinary care involving various specialists to address potential physical, developmental, and medical challenges.
References
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- Botto LD, Moore CA, Khoury MJ. Neural-tube defects. The New England journal of medicine. 1999. PMID: 10559453
- Robinson S, Kaufman BA, Jane JA Jr. Introduction: neural tube defects. Neurosurgical focus. 2012. PMID: 23025447
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- Neural-tube defects. Lancet (London, England). 1978. PMID: 75343
- V RP, Finnell RH, Ross ME. Neural tube defects and epigenetics: role of histone post-translational histone modifications. Epigenomics. 2024. PMID: 38410929
- Vitamins, neural-tube defects, and ethics committees. Lancet (London, England). 1980. PMID: 6103394