Genetic investigations in cerebral palsy.

Abstract

The original description of cerebral palsy (CP) contained case histories suggesting that perinatal environmental stressors resulted in brain injury and neurodevelopmental disability. While there are clear associations between environmental impact on brain development and CP, recent studies indicate an 11% to 40% incidence of monogenic conditions in patients given a diagnosis of CP. A genetic diagnosis supports the delivery of personalized medicine. In this review, we describe how the Wnt pathway exemplifies our understanding of pathophysiology related to a gene variant (CTNNB1) found in some children diagnosed with CP. We cover studies undertaken to establish the baseline prevalence of monogenic conditions in populations attending CP clinics. We list factors indicating increased likelihood of a genomic diagnosis; and we highlight the need for a comprehensive, accurate, genotype-phenotype reference data set to aid variant interpretation in CP cohorts. We also consider the wider societal implications of genomic management of CP including significance of the diagnostic label, benefits and pitfalls of a genetic diagnosis, logistics, and cost.