The Genetic Basis of Hydrocephalus.


Journal Article (Review)

Studies of syndromic hydrocephalus have led to the identification of >100 causative genes. Even though this work has illuminated numerous pathways associated with hydrocephalus, it has also highlighted the fact that the genetics underlying this phenotype are more complex than anticipated originally. Mendelian forms of hydrocephalus account for a small fraction of the genetic burden, with clear evidence of background-dependent effects of alleles on penetrance and expressivity of driver mutations in key developmental and homeostatic pathways. Here, we synthesize the currently implicated genes and inheritance paradigms underlying hydrocephalus, grouping causal loci into functional modules that affect discrete, albeit partially overlapping, cellular processes. These in turn have the potential to both inform pathomechanism and assist in the rational molecular classification of a clinically heterogeneous phenotype. Finally, we discuss conceptual methods that can lead to enhanced gene identification and dissection of disease basis, knowledge that will potentially form a foundation for the design of future therapeutics.

Full Text

Cited Authors

  • Kousi, M; Katsanis, N

Published Date

  • July 8, 2016

Published In

Volume / Issue

  • 39 /

Start / End Page

  • 409 - 435

PubMed ID

  • 27145913

Pubmed Central ID

  • 27145913

Electronic International Standard Serial Number (EISSN)

  • 1545-4126

Digital Object Identifier (DOI)

  • 10.1146/annurev-neuro-070815-014023


  • eng

Conference Location

  • United States