The search for genetic determinants of human neural tube defects

An update is presented regarding neural tube defects (NTDs) including spina bifida and anencephaly, which are among the most common serious birth defects world-wide. Decades of research suggest that no single factor is responsible for neurulation failure, but rather NTDs arise from a complex interplay of disrupted gene regulatory networks, environmental influences and epigenetic regulation. A comprehensive understanding of these dynamics is critical to advance NTD research and prevention.

Next-generation sequencing has ushered in a new era of genomic insight toward NTD pathophysiology, implicating novel gene associations with human NTD risk. Ongoing research is moving from a candidate gene approach toward genome-wide, systems-based investigations that are starting to uncover genetic and epigenetic complexities that underlie NTD manifestation.

Neural tube closure is critical for the formation of the human brain and spinal cord. Broader, more all-inclusive perspectives are emerging to identify the genetic determinants of human NTDs.