Neural Tube Defects: Genetics

Abstract Neural tube defects (NTDs) are malformations of the brain and the spinal cord, resulting from lack of closure of the developing neural tube during embryological development. NTDs are complex birth disorders with a worldwide prevalence from 0.5 to 2.0 per 1000 births. The two most common types of NTD are anencephaly and spina bifida, which involve failure of neural tube closure in the cranial and in the back regions respectively. NTDs are hypothesised to be a result of genetic abnormalities and environmental factors; yet, the aetiology remains undetermined. Research studies over the past decade have indicated that maternal folate deficiency is an extremely important risk factor for an NTD birth, with maternal folate supplementation decreasing risk. However, the role that folate plays in NTD risk is not well defined. Key Concepts: Neural tube defects (NTDs) are congenital malformations of the brain and spinal cord. The prevalence rates of NTDs vary worldwide. NTDs are complex birth defects composed of both genetic and environmental components. The underlying mechanism remains undetermined. NTDs are classified by whether they are open or closed and by the location of the lesion. Folic acid supplementation ameliorates NTD risk. The majority of NTDs are sporadic and nonsyndromic. To date, association studies in relatively small patient cohorts have been used in an attempt to find causative genes. Future additional approaches will include Genome‐Wide Association Study (GWAS) and high‐throughput sequencing.