We are beginning to understand the molecular biology of hydrocephalus and its related diseases. X-linked hydrocephalus (XLH), holoprosencephaly (HPE), Dandy–Walker malformation (DWM), and neural tube defect (NTD) can all be discussed with respect to their available molecular genetics knowledge base and its clinical applications. XLH is single gene disorder caused by mutations in the neural cell adhesion molecule-encoding
L1CAM (L1) gene
. Our knowledge of the molecular basis of XLH is already being applied clinically in disease diagnosis, disease classification, and prenatal diagnosis. However, the molecular mechanism underlying XLH-related hydrocephalus still needs to be clarified. Sixteen causative genes for HPE have been identified, of which mutations are most often found in
SHH, ZIC2, SIX3, and
TGIF. Genetic interactions, gene complexity, and the wide variety of HPE phenotypes and genotypes are topics for future study. For DWM, two important loci, 3q24, which includes the
FOXC1 gene, and 6q25.3, which includes the
ZIC1 and
ZIC4 genes, were recently identified as causative areas. The planar cell polarity (PCP) genes
CELSR1, CELSR2, VANGL1, and
VANGL2 have been implicated in NTD; these genes have roles in neural tube closure and ependymal ciliary movement.
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