Next-Generation Sequencing (NGS) in Pediatric Patients with Epilepsy: How Many Previously Unsolved Cases Can Be Solved?

Background/Purpose: Modern sequencing methods (next-generation sequencing [NGS]) revolutionized the field of pediatric epileptology over the last decade. Gene panel testing, as well as whole-exome sequencing (WES), a technique for sequencing all protein-coding regions of genes in the genome, contribute to solving previously unsolved cases with clinically unspecific phenotypes.

Methods: We conducted a retrospective data analysis in which all cases of previously unsolved pediatric patients with epileptic encephalopathies (EE) were included, whose datasets had been analyzed at the Institute of Human Genetics in Graz. The cohort of altogether 56 patients was divided in two subgroups, in which patients were assigned, depending on whether or not they presented additional clinical features. Data analysis was performed either by using a virtual epilepsy gene testing panel or by assessing the whole dataset in view of specific human phenotype ontology (HPO) terms.

Results: Overall, 18 (32.1%) of the 56 patients presented with isolated EE without no further clinical features, whereas 38 patients (67.9%) met at least two HPO terms. In the subgroup of patients with isolated epilepsy only 4 (22.2%) received a diagnosis after genetic testing, leaving 14 (77.8%) cases yet to be solved, whereas in the subgroup with additional clinical features 15 (39.5%) cases could be solved, while 23 (60.5%) cases remained unsolved.

Conclusion: Our retrospective data analysis showed that the detection rate of genetic testing in pediatric patients with EE is higher in those with additional clinical features. This underscores the importance of deep phenotyping and a close collaboration between geneticists and clinicians to solve as many cases as possible.

Publication History

Article published online:
28 October 2021