A Dynamic Genetic Testing Approachment for Neurological Disorders in The Pediatric Neurogenetic Case-Management Councils

Objective: Early establishment of a genetic diagnosis is necessary for optimizing management and treatment options in neurological disorders. However, it is unclear which genetic testing strategy is best for maximizing diagnostic yield. Clinicians are challenged with complex clinical algorithms for choosing the best genetic workup and with test result interpretation. In the evaluation of complex genetic cases, councils with genetics and neurology specialists are important. We aimed to evaluate the diagnostic yield of genetic tests and neuro-genetics councils using a dynamic approach for neurological disorders with enrichment using genetic databases. Methods: A case series including 61 patients with diagnosis of a neurological disorder was evaluated at the Pediatric Neurogenetic Case-Management Councils at Children’s Hospital of Ege University. Genetic testing to reveal etiology (karyotyping, micro-array, gene panels, clinic exome, and whole-exome sequencing) on patients and whole-exome trio analysis were discussed during case management councils. Results: Among the 61 patients, 21 patients (34.4%) had a genetic molecular diagnosis using dynamic testing approaching after initial genetic analysis. Thirty-seven (60.6%) cases are still under evaluation for additional genetic testing or reanalysis of sequencing data. Only 3 patients (5%) completed the neurogenetic case management evaluation without a specific molecular diagnosis. Conclusion: This dynamic approach provides more specific molecular diagnosis and precision treatment in children with neurological disorders. A successive genetic workup should include parental testing of selected probands and whole-exome trio analysis in the presence of inconclusive cases. Follow-up reanalysis is needed to achieve a specific diagnosis and capture information on newly identified disease genes.
Keywords: Neurogenetic, pediatric neurogenetic councils