Genomic findings in non-cryptogenic cerebral palsy: a systematic review and meta-analysis.
About 1 in 8 people with non-cryptogenic cerebral palsy have pathogenic genomic findings.
Genomic findings in non-cryptogenic cerebral palsy: a systematic review and meta-analysis.
The contribution of genomic variants to non-cryptogenic cerebral palsy (cerebral palsy), defined by identifiable perinatal or acquired risk factors, remains incompletely characterized.
This study aimed to estimate the frequency of reported pathogenic or likely pathogenic (P/LP) genomic findings in non-cryptogenic cerebral palsy and compare it with cryptogenic cohorts.
We conducted a systematic review and meta-analysis searching PubMed and Scopus to May 30, 2026, for sequencing-based cerebral palsy studies with extractable non-cryptogenic data.
genetic testing found a likely cause in about 1 in 8
In seven studies with cryptogenic subgroup data, the pooled frequency was 32.3% (95% CI 21.0-46.1; I 2 = 69.9%).
Cryptogenic cases were more than twice as likely to have a reported P/LP genomic finding as non-cryptogenic cases (risk ratio 2.21, 95% CI 1.56-3.14).
Across all analyzed cohorts, the overall pooled frequency was 19% (95% CI 12-28).
Prematurity was generally associated with lower frequencies, whereas selected hemorrhagic or cerebrovascular phenotypes showed enrichment for COL4A1/COL4A2- related findings.
Reported P/LP genomic findings occur in a clinically meaningful subset of individuals with non-cryptogenic cerebral palsy, although less frequently than in cryptogenic cerebral palsy.
Interpretation is limited by heterogeneous definitions of non-cryptogenic cerebral palsy and incomplete genotype-phenotype adjudication across studies.
These findings support careful assessment of perinatal risk factors, neuroimaging patterns, and genotype-phenotype concordance when interpreting genomic results.