In the first installment of the genetic links to hydrocephalus we discussed non-syndromic autosomal recessive hydrocephalus. Here we will be looking at the genetics of neural tube defects, which can lead to hydrocephalus.
The neural tube is the precursor for the brain and spinal cord in developing embryos. Its formation involves fusion of a layer of cells known as the neural plate. Neural tube defects are a result of the abnormal closure of the neural plate. Such defects can lead to hydrocephalus. There are currently two genetic hypotheses in regard to the role of genetics in NTDs: variants in genes involved in planar cell polarity and genes involved in the folate metabolic pathway. In our last genetics blog we talked about the importance of planar cell polarity to normal cell behavior.
Planar cell polarity (PCP) is the proper alignment of cells and their coordinated orientation. This is coordinated by the PCP pathways, which consequently play a role in the coordination of cell behaviors such as proper maintenance of the cell cycle. PCP has been shown to be vital in the closure of the neural tube. FUZ, VANGL1, VANGL2, and CCLZ are genes involved with PCP and PCP pathways. Abnormalities to neural tube defects are linked to neural tube defects, presumably due to the importance of PCP in the closure of the neural tube. PCP, as you can see, seems to play many important roles in the development of hydrocephalus. In fact, it was one of the very interesting topics discussed at our recent Post hemorrhagic Hydrocephalus Workshop.
The nutrient folate (or folic acid) is essential for normal cell growth and cell division, and by extension human development. Studies have shown that irregular folate metabolism and the development of the neural tube are directly linked. This is most likely be due the large role folate plays in development and in DNA synthesis. MTR, MTRR, MTHFR, and MTHFD are all genes which code for proteins involved in proper metabolism and transport of folate; variants in these genes are thus thought to be linked to the incidence of NTDs. Taking folic acid supplements before and during pregnancy has been found to reduce the likelihood of Spina Bifida (a type of neural tube defect), which is why the CDC recommends that ALL women be taking folate!