Spina bifida and other neural tube defects

Abstract

NTDs, resulting from failure of the neural tube to close during the fourth week of embryogenesis, are the most common severely disabling birth defects in the United States, with a frequency of approximately 1 of every 2000 births. Neural tube malformations involving the spinal cord and vertebral arches are referred to as spina bifida, with severe types of spina bifida involving protrusion of the spinal cord and/or meninges through a defect in the vertebral arch. Depending on the level of the lesion, interruption of the spinal cord at the site of the spina bifida defect causes paralysis of the legs, incontinence of urine and feces, anesthesia of the skin, and abnormalities of the hips, knees, and feet. Two additional abnormalities often seen in children with spina bifida include hydrocephalus and the Arnold-Chiari type II malformation. Despite the physical and particular learning disabilities children with spina bifida must cope with, participation in individualized educational programs can allow these children to develop skills necessary for autonomy in adulthood. Advances in research to uncover the molecular basis of NTDs is enhanced by knowledge of the link between both the environmental and genetic factors involved in the etiology of NTDs. The most recent development in NTD research for disease-causing genes is the discovery of a genetic link to the most well-known environmental cause of neural tube malformation, folate deficiency in pregnant women. Nearly a decade ago, periconceptional folic acid supplementation was proven to decrease both the recurrence and occurrence of NTDs. The study of folate and its association with NTDs is an ongoing endeavor that has led to numerous studies of different genes involved in the folate metabolism pathway, including the most commonly studied thermolabile mutation (C677T) in the MTHFR gene. An additional focus for NTD research involves mouse models that exhibit both naturally occurring NTDs, as well as those created by experimental design. We hope the search for genes involved in the risk and/or development of NTDs will lead to the development of strategies for prevention and treatment. The most recent achievement in treatment of NTDs involves the repair of meningomyelocele through advancements in fetal surgery. Convincing experimental evidence exists that in utero repair preserves neurologic function, as well as resolving the hydrocephalus and Arnold-Chiari malformation that often accompany meningomyelocele defects. However, follow-up is needed to completely evaluate long-term neurologic function and overall improved quality of life. And in the words of Olutoye and Adzick, "until the benefits of fetal [meningomyelocele] repair are carefully elucidated, weighed against maternal and fetal risks, and compared to conventional postnatal therapy, this procedure should be restricted to a few centers that are committed (clinically and experimentally) to investigating these issues."