Systematic Review on Genetic Variants in Children With Cerebral Palsy

Area of Science:

• Genetics
• Pediatrics
• Neurology

Background:

• Cerebral palsy (CP) is a complex neurological disorder with diverse etiologies.
• Understanding the genetic underpinnings of CP is crucial for accurate diagnosis and management.
• Previous genetic studies in CP have varied in scope and methodology.

Purpose of the Study:

• To provide a comprehensive overview of genetic findings in pediatric cerebral palsy.
• To describe genetic variants, subtypes, comorbidities, and neuroimaging correlations.
• To assess the clinical utility of genetic testing in cerebral palsy.

Main Methods:

• Systematic literature review of Embase and Medline databases (2000-2022).
• Inclusion of studies with at least 10 individuals diagnosed with cerebral palsy.
• Analysis of genetic variants, copy number variations (CNVs), and associated phenotypes.

Main Results:

• Nineteen studies comprising 3707 individuals with CP were analyzed.
• Overall diagnostic yield of genetic testing was 22.2%, reaching 55% in cryptogenic CP.
• Identified variants in 377 genes (e.g., CTNNB1, SPAST, ATL1) and 59 CNVs, including known microdeletion/duplication syndromes. Spastic and dyskinetic CP were common phenotypes.

Conclusions:

• Genetic evaluation is vital for diagnostic clarification, targeted therapies, and comorbidity monitoring in CP.
• Genetic testing offers significant benefits for management and prevention, especially in cryptogenic cases.
• Genetic findings correlate with epilepsy, neuroimaging patterns, and treatable conditions, underscoring the need for genetic counseling.