Insights From Genetic Studies of Cerebral Palsy

Cohort-based whole exome and whole genome sequencing and copy number variant (CNV) studies have identified genetic etiologies for a sizable proportion of patients with cerebral palsy (CP). These findings indicate that genetic mutations collectively comprise an important cause of CP. We review findings in CP genomics and propose criteria for CP-associated genes at the level of gene discovery, research study, and clinical application. We review the published literature and report 18 genes and 5 CNVs from genomics studies with strong evidence of for the pathophysiology of CP. CP-associated genes often disrupt early brain developmental programming or predispose individuals to known environmental risk factors. We discuss the overlap of CP-associated genes with other neurodevelopmental disorders and related movement disorders. We revisit diagnostic criteria for CP and discuss how identification of genetic etiologies does not preclude CP as an appropriate diagnosis. The identification of genetic etiologies improves our understanding of the neurobiology of CP, providing opportunities to study CP pathogenesis and develop mechanism-based interventions.

Automated summary

Genetic mutations play an important role in cerebral palsy, affecting the pathophysiology, with published results and criteria already established; Genes associated with CP can disrupt early brain development and are linked to environmental risk factors, as well as overlapping with other neurodevelopmental disorders; Identification of genetic etiologies improves our understanding of CP neurobiology, paving the way for mechanism-based interventions in the future.