Mutations in the L1 gene result in the X-linked L1 Syndrome, which encompasses several neurological conditions. However, there is much variability in penetrance and expressivity of these conditions, especially hydrocephalus, within families, thus pointing to important influence of genetic modifiers. These researchers have identified several genetic interactors of L1 in Caenorhabditis elegans that cause synergistic as well as synthetic phenotypes. Several such genetic interactions result in synthetic fluid dyregulation. Intriguingly, mutations in these genetic interactors also cause hydrocephalus with varying penetrance and expressivity. The goal of this project is to screen the exomes of 400 hydrocephalus patients from dbGaP for double hits of L1 and the genetic interactors identified in C. elegans to determine whether these genetic interactions promote hydrocephalus in humans.