Advances in Genetic Discoveries in Cerebral Palsy: Implications for Diagnosis, Prognosis, and Counseling

This review examines the expanding role of genetic factors in cerebral palsy (CP), with a focus on cryptogenic presentations and CP-masquerading conditions. It addresses how genomic insights refine diagnosis, guide management, and influence counseling.

Emerging evidence demonstrates that de novo single-nucleotide variants, copy number variants, mitochondrial variants, and, rarely, repeat expansions contribute significantly to CP, particularly when neuroimaging is normal, progression is atypical, or additional neurodevelopmental features are present. Diagnostic yield is highest in these contexts. Trio-based whole-exome sequencing is recommended as first-line testing, supported by chromosomal microarray or whole-genome sequencing. Integration of genomic testing remains limited by inconsistent CP definitions, restricted test access, and under-recognition of genetic etiologies, especially in adults. Standardized CP classification frameworks, such as SCPE (Surveillance of Cerebral Palsy in Europe), combined with early genomic evaluation, can improve diagnostic accuracy, reveal treatable conditions, and enable precision care. This approach has potential to transform management and outcomes across the lifespan.