Unraveling The Genetic Landscape of Cerebral Palsy: Implications For Diagnosis and Personalized Care

Background / Objectives. Genetic factors are believed to contribute to 10-55% of cerebral palsy (CP). Although understanding of CP's clinical aspects has improved, its genetic origins remain largely uncharted. This study aims to investigate the genomic attributes of CP in children and their relation to clinical traits. Patients and Methods. A retrospective review of the Ege University Child Neurology Patients Data Set involved 755 children with CP. Among them, 48 CP patients (6.4%) underwent genetic testing. They were categorized into GroupI (n=5): cryptogenic CP (CPc), GroupII (n=6): non-cryptogenic CP (CPnc), and GroupIII (n=37): CP masqueraders (CPm). The study analyzed features, motor phenotypes, comorbidities, and brain MRIs, evaluating the diagnostic rates of genetic tests and their impact on patient management. Results. The spastic-CP subtype was most common (n=22), followed by mixed and dyskinetic-CP subtypes (n=17 and n=9, respectively). Genetic causes were identified in 47.9% of patients (23 out of 48), with the highest yield in the dyskinetic subtype (75%). Genetic diagnoses directly influenced treatment for 34.7% of patients, with whole exome sequencing (WES) in nine and targeted gene panels leading to diagnoses in eight patients. Differences between CP subgroups with genetic or non-genetic diagnoses are summarized in Table 1. Conclusion. This study highlights a significant genetic contribution to CP, with pathogenic variants identified in 47.9% of cases undergoing genetic testing. These findings underscore the importance of genetic testing, especially in patients with CP masqueraders and the dyskinetic subtype, for more personalized treatment care.