Exome sequencing should be used for diagnosing cerebral palsy | Image Credit: © Contemporary Pediatrics - © Contemporary Pediatrics - stock.adobe.com.
- High Diagnostic Success: Exome/genome sequencing in cerebral palsy (CP) yields genetic diagnoses in 31.1% of cases, comparable to other disorders, with higher rates in pediatric and comorbid cases.
- Inclusion in Recommendations: CP should be included in first-tier diagnostic sequencing, broadening the scope beyond typical cases and regardless of comorbid conditions.
- Pediatric Emphasis: Pediatric CP cases, including those with known causes like prematurity, show positive genetic results, emphasizing the relevance of genetic testing in these scenarios.
- Expanded Testing Scope: Dr. Farber stresses the need to consider CP in genetic testing protocols, indicating a shift in clinical practice based on these findings.
- Genetic Testing Urgency: CP patients, even with apparent causes, benefit from genetic testing, highlighting the urgency to implement it as a standard diagnostic tool.
Is the diagnostic yield of exome or genome sequencing (GS) in cerebral palsy (CP) similar to that of other neurodevelopmental disorders for which exome sequencing (ES) is recommended as a first-tier clinical diagnostic test? A systematic review and meta-analysis found that such sequencing indeed has an equivalent high genetic diagnostic yield in CP, which supports including this neurodevelopmental disorder among those for which diagnostic ES should be used.
This conclusion was based on the findings of 13 studies in adults and children (2 studies reported adult and pediatric groups separately) related to CP and genetic testing, comprising a total of 2,612 individuals with CP. Analysis showed a genetic diagnostic yield of ES/GS in CP of 31.1% (similar to other neurodevelopmental disorders), with the highest yield—34.8%— in pediatric groups. The diagnostic yield was even higher (37.8%) in individuals with comorbid intellectual disability and developmental delay. Given these findings, investigators called for inclusion of CP in current recommendations to use ES as a first-tier test for individuals with neurodevelopmental disorders, without regard to their comorbidities or risk factors.
THOUGHTS FROM DR FARBER:
Positive findings were seen even in children with “obvious” explanations for their cerebral palsy, such as prematurity. Add cerebral palsy to your list of diagnoses that warrant genetic testing.
Click here for more from the October 2023 issue of Contemporary Pediatrics®.
Gonzalez-Mantilla PJ, Hu Y, Myers SM, et al. Diagnostic yield of exome sequencing in cerebral palsy and implications for genetic testing guidelines. A systematic review and meta-analysis. JAMA Pediatr. 2023;177(5):472-478. doi:10:1001/jamapediatrics.2023.0008