Genetic testing in paediatric neurological disorders

Area of Science:

• Pediatric Neurology
• Clinical Genetics
• Genomic Medicine

Background:

• Genetic testing is crucial for diagnosing rare pediatric neurological disorders.
• Evaluating different genetic testing modalities is essential for optimizing diagnostic strategies.

Purpose of the Study:

• To compare the diagnostic yield of exome sequencing, commercial gene panels, and in-house gene panels.
• To identify clinical predictors of pathogenic genetic variants in pediatric neurological conditions.
• To assess the clinical utility of genetic testing in a large tertiary hospital setting.

Main Methods:

• Retrospective cohort study of pediatric patients (<18 years) with neurological disorders, epilepsy, or movement disorders.
• Analysis of genetic testing data from 2020-2023, including exome sequencing and various gene panels.
• Logistic regression to identify clinical features associated with positive genetic testing results.

Main Results:

• Exome sequencing demonstrated the highest pathogenic yield (39%) compared to epilepsy (28%), movement disorder (25%), and commercial panels (15%).
• Developmental delay, intellectual disability, and epilepsy were common clinical features in the exome sequencing cohort.
• Genetic testing significantly informed clinical decision-making in 49% of cases within the exome sequencing group.

Conclusions:

• Exome sequencing is superior to gene panels for diagnosing genetic causes of pediatric neurological disorders.
• Clinical features like severe developmental delay and hypotonia are associated with pathogenic variants.
• The findings underscore the importance of establishing robust local genetic testing capabilities.