169 - Pathophysiology of NeuralTube Defects

Abstract

Neural tube defects (NTDs) are common malformations of the brain and spinal cord that vary from lethal to asymptomatic and cause considerable perinatal death and childhood disability. Open NTDs, principally anencephaly and open spina bifida, arise in the fourth week after conception due to failure of embryonic neural tube closure. Secondary neurulation (neural tube formation by canalization) is implicated in skin-covered low spinal defects, while brain herniation is responsible for encephalocele. Classification of NTDs is currently based on morphologic appearance, and nomenclature is confusing as it varies between scientific and medical disciplines. Some NTDs are syndromic, for example, as part of a chromosomal disorder, whereas the majority are sporadic and nonsyndromic. Both genetic and environmental factors contribute to the causation of sporadic NTDs, with probable multifactorial causation in most cases. Several environmental factors increase NTD risk, including the anticonvulsant valproic acid and the fungal toxin fumonisin. Among genes implicated in NTDs are those of the planar cell polarity pathway and mitochondrial folate metabolism. Developmental studies in mouse genetic models show that NTDs can arise from faulty neural plate shaping, bending and fusion of the neural folds. NTDs are routinely diagnosed prenatally by ultrasound and repaired surgically immediately after birth, or by a fetal surgery approach. The NTD birth prevalence has reduced in countries that practice pregnancy termination while primary prevention of a proportion of NTDs is possible through folic acid supplementation in early pregnancy, and by a public health strategy involving fortification of staple foods with folate.