The genomic basis of cerebral palsy: a HuGE systematic literature review

Hum Genet. 2009 Jul;126(1):149-72. doi: 10.1007/s00439-009-0638-5. Epub 2009 Feb 24.


Cerebral palsy has been associated with a number of candidate genes. To date, no systematic review has been conducted to synthesise genetic polymorphism associations with cerebral palsy. We apply the HuGE NET guidelines to search PubMed and EMBASE databases for publications investigating single nucleotide polymorphisms (SNPs) and cerebral palsy outcome. 22 papers were identified and are discussed in this review. Candidate genes were grouped as (1) thrombophilic, (2) cytokine, (3) apolipoprotein E or (4) other SNPs, largely related to cardiovascular physiology/pathophysiology and the functioning of the immune system. Of the studies identified, cohorts were usually small, without adequate control and ethnically diverse, making direct comparison between studies difficult. The most promising candidate genes include factor V Leiden, methylenetetrahydrofolate reductase, lymphotoxin-alpha, tumour necrosis factor-alpha, eNOS and mannose binding lectin. Large case-control studies are needed to confirm these candidates with attention given to cohort ethnicity, cerebral palsy subtype analysis and possible multiple gene and gene-environment interactions.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Apolipoproteins E / genetics
  • Case-Control Studies
  • Cerebral Palsy / genetics*
  • Cohort Studies
  • Databases, Factual
  • Factor V / genetics
  • Forecasting
  • Guidelines as Topic*
  • Humans
  • Lymphotoxin-alpha / genetics
  • Mannose-Binding Lectin / genetics
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics
  • Nitric Oxide Synthase Type III / genetics
  • Polymorphism, Single Nucleotide
  • Tumor Necrosis Factor-alpha / genetics


  • Apolipoproteins E
  • Lymphotoxin-alpha
  • Mannose-Binding Lectin
  • Tumor Necrosis Factor-alpha
  • factor V Leiden
  • Factor V
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III
  • Methylenetetrahydrofolate Reductase (NADPH2)