Exome sequencing findings in patients with cerebral palsy

Objective. To evaluate the diagnostic efficacy of whole exome sequencing in individuals with various forms of cerebral palsy (CP). Material and methods. An open-label observational study was conducted from 2018 to 2025, including 502 patients with CP aged 4 to 18 years. The cohort comprised 307 males (61.2%) and 195 females (38.8%). Diagnoses included spastic CP in 332 patients (66.2%), dyskinetic CP in 95 patients (18.9%), and ataxic CP in 75 patients (14.9%). The genetic analysis employed whole exome sequencing and the trio Sanger sequencing. Results. Clinically significant genetic variants were detected in 165 patients (32.9%). The effectiveness of molecular diagnostics varied significantly by clinical subtype of CP. The highest efficacy of 77.3% was observed in patients with ataxic CP. Efficacy in dyskinetic CP was 47.4%, while in spastic CP, it was 18.7%. In patients with CP who also presented with epilepsy, the frequency of a genetic variant was 12.8 times greater than in those without epilepsy. Similarly, patients with CP and intellectual disabilities had a 6.4-fold increased frequency of genetic variants compared to their counterparts without intellectual disabilities. Additionally, variants were discovered in genes not previously reported. Conclusions. The results from this study may enhance the understanding of the genetic mechanisms underlying the various forms of CP. The identification of a genetic etiology in CP patients is crucial for accurately determining the disease’s origin, facilitating proper nosological classification, aiding in differential diagnosis, and offering genetic counseling to patients and their families to assess the risk of CP in future offspring.