ImportanceThere are many known acquired risk factors for cerebral palsy (CP), but in some cases, CP is evident without risk factors (cryptogenic CP). Early CP cohort studies report a wide range of diagnostic yields for sequence variants assessed by exome sequencing (ES) and copy number variants (CNVs) assessed by chromosomal microarray (CMA).ObjectiveTo synthesize the emerging CP genetics literature and address the question of what percentage of individuals with CP have a genetic disorder via ES and CMA.Data SourcesSearched articles were indexed by PubMed with relevant queries pertaining to CP and ES/CMA (query date, March 15, 2022).Study SelectionInclusion criteria were as follows: primary research study, case series with 10 or more nonrelated individuals, CP diagnosis, and ES and/or CMA data used for genetic evaluation. Nonblinded review was performed.Data Extraction and SynthesisPreferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used for assessing data quality and validity. Data were extracted by a single observer.Main Outcomes and MeasuresA separate meta-analysis was performed for each modality (ES, CMA). The primary outcome was proportion/molecular diagnostic yield (number of patients with a discovered genetic disorder divided by the total number of patients in the cohort), evaluated via meta-analysis of single proportions using random-effects logistic regression. A subgroup meta-analysis was conducted, using risk factor classification as a subgroup. A forest plot was used to display diagnostic yields of individual studies.ResultsIn the meta-analysis of ES yield in CP, the overall diagnostic yield of ES among the cohorts (15 study cohorts comprising 2419 individuals from 11 articles) was 23% (95% CI, 15%-34%). The diagnostic yield across cryptogenic CP cohorts was 35% (95% CI, 27%-45%), compared with 7% (95% CI, 4%-12%) across cohorts with known risk factors (noncryptogenic CP). In the meta-analysis of CMA yield in CP, the diagnostic yield of CMA among the cohorts (5 study cohorts comprising 294 individuals from 5 articles) was 5% (95% CI, 2%-12%).Conclusions and RelevanceResults of this systematic review and meta-analysis suggest that for individuals with cryptogenic CP, ES followed by CMA to identify molecular disorders may be warranted.