Neural Tube Defects, Molecular Biology of

Spina bifida is usually grouped together with the closely related conditions anencephaly and craniorachischisis, to form the category of congenital malformations known as neural tube defects (NTDs). NTDs affect approximately 1 in every 1000 pregnancies, equating to a worldwide prevalence of around 120 000 pregnancies with NTDs per year. Hence, NTDs represent one of the commonest, most severe birth defects in humans. The term NTDs reflects the origin of the malformations. In normal development, the neural plate, the precursor of the brain and spinal cord in the early embryo, undergoes folding and fusion to form the neural tube. If neural tube closure fails in the developing spine, the result is open spina bifida (also called myelomeningocele or myelocele; Fig. 1(a)–(d)), a defect in which the interior of the spinal cord remains open to the outside, rather than being covered by the bony vertebrae and skin. The exposed nervous tissue degenerates before birth so that babies born with open spina bifida are often paralysed and lack sensation below the level of the lesion. They may exhibit urinary and faecal incontinence, and have associated defects such as hydrocephalus (Fig. 1(e)). If the neural tube fails to close in the embryonic brain, the resulting birth defect is initially described as exencephaly (Fig. 1(b)), in which the neural folds appear everted. Later in gestation, degeneration of the neural tissue converts the defect to anencephaly, in which the interior of the skull is exposed owing to loss of the open brain and failure of the skull roof to develop. Fetuses with anencephaly do not survive beyond birth, and are often stillborn or die during pregnancy. If the entire neural tube fails to close, from brain to low spine, this is referred to as craniorachischisis (Fig. 1(f)–(h)), a uniformly lethal condition. Closed spina bifida (also called spina bifida occulta) represents the mild end of the NTD spectrum. The lowest part of the spinal cord fails to separate from adjacent tissues during development, a defect that can produce weakness of the legs or urinary incontinence. Surgical intervention may be required in order to free the spinal cord within the vertebral canal, relieving pressure on the spinal nerve roots.