Genetic testing in individuals with cerebral palsy

Area of Science:

• Genetics
• Neurology
• Pediatrics

Background:

• Cerebral palsy (CP) is a complex condition with both genetic and environmental influences.
• Identifying the etiology of CP is crucial for diagnosis, prognosis, and management.
• Genetic testing is increasingly used, but its utility in relation to environmental risk factors is not fully understood.

Purpose of the Study:

• To compare the diagnostic yield of genetic testing in patients with cerebral palsy (CP) based on the presence or absence of environmental risk factors.
• To investigate whether environmental risk factors influence the likelihood of identifying causative genetic variants in CP.

Main Methods:

• Whole-exome sequencing was performed on 151 individuals with CP.
• Participants were assessed for environmental risk factors including extreme preterm birth, brain injury, birth asphyxia, brain malformations, and intrauterine infection.
• The rate of likely causative genetic variants was compared between individuals with and without these risk factors.

Main Results:

• Causative genetic variants were identified in 9.3% of all participants.
• The diagnostic rate of genetic variants was 8.1% in individuals with environmental risk factors and 14.3% in those without.
• This difference in diagnostic rates was not statistically significant (Fisher's exact p=0.3).
• Six novel causative variants in genes not previously linked to CP were identified.

Conclusions:

• The study found no significant difference in the rate of genetic diagnoses for cerebral palsy (CP) between patients with and without environmental risk factors.
• Genetic variants may play a role in susceptibility to environmental factors contributing to CP.
• Global developmental delay/intellectual disability is associated with a genetic cause, while extreme preterm birth, stroke, and older age are negatively associated.