Neural tube defects (NTD) are congenital defects of the brain and spinal cord, caused by incomplete closure of the embryonic neural tube during the first few weeks of development. Different forms of NTDs depend on the portion of the neural tube left open. Spina bifida results from the spinal cord remaining incomplete, in addition to the vertebra overlying the open portion of the cord also remaining unfused. As a result, the incomplete spinal cord pushes out through the opening in the bones. In anencephaly, it is the cerebral part of the neural tube that does not close. Different forms of spina bifida can also be seen. In its mildest form, known as spina bifida occulta, only the bone of the vertebra do not close. However, the meninges and spinal cord are normal. Such cases may actually go undetected, with affected people leading a normal, asymptomatic life, apart from back pain and a predisposition to herniation in some. Myelomeningocele and meningocele are more serious forms, in which the meninges and other tissue protrude out through the opening. Typical symptoms of spina bifida include paralysis of the nerves below the affected area, causing ambulatory difficulties, lack of bladder and bowel control, loss of sensation to some areas of the body, deformities of the hips, knees, and feet, loss of muscle tone, mental retardation, and seizures. In severe cases, the disease is fatal immediately after birth.
Racial, geographic and seasonal variations seem to affect the incidence of NTDs. The greatest risk factor for development of spina bifida is recognized as low blood folate level in the mother during the first four weeks of embryonal development. All women of child-bearing age are therefore, recommended to intake at least 400 micrograms of folic acid each day. On the other hand, case reports and epidemiologic studies have implicated a number of chemicals, widely differing therapeutic drugs, environmental contaminants, pollutants, infectious agents, and solvents. Maternal hyperthermia, use of valproate by epileptic women during pregnancy, deficiency and excess of certain nutrients and chronic maternal diseases (e.g. diabetes mellitus) are reported to cause a manifold increase in the incidence of NTD.
Prenatal diagnosis of the condition is possible by way of an ultrasound scan of the fetus late in the pregnancy. However, in early stages, a high level of alpha fetoprotein in the amniotic fluid can also be used as an indication for the condition. Milder versions of the disease do not require any treatment. However, more serious conditions may require surgery to prevent further complications.
The genetic nature of NTD is exemplified by an increased risk of developing the condition in families with a history of the disease. However, no Mendelian pattern of inheritance has been reported. It has been observed that a genetic component most notably increases the rate of recurrence of the condition in siblings and in the offspring of an affected person. Several genes have been identified to be associated with spina bifida. These include VANGL1, VANGL2, CELSR1, FUZ and the C677T polymorphism of the MTHFR gene. NTDs are also known to be a feature of chromosomal conditions like trilogy 13, trisomy 18, and certain chromosomal rearrangements.