Molecular Diagnosis in Children With Febrile Seizures: Beyond the Conventional Clinical Classification

Panel of 189 genes associated with fever-induced seizures, variants classified according to ACMG guidelines

This nationwide, multicenter prospective cohort study, conducted from January 2019 to February 2023, enrolled 3,300 children with a clinical diagnosis of febrile seizures, of whom 2,552 were analyzed with a 189-gene panel. Two hundred and seventy-three received a positive diagnosis, an 11% yield, with the top ten genes accounting for 70.4% of diagnoses. Yield did not differ significantly between simple (9.5%; 111 of 1,163) and complex febrile seizures (11.7%; 162 of 1,389; p = 0.085). Molecular diagnosis influenced management in 76.2% of cases and prognosis in 72.6%, at a cost of 240 dollars per three-person family and a 14-day turnaround.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The striking finding is a negative one: the simple versus complex distinction, which structures clinical decisions, does not predict the presence of a genetic fever-sensitive epilepsy, arguing against restricting testing to complex forms. The impact on management is investigator-reported rather than measured on clinical endpoints, and 23% of enrolled children were not analyzed, which may bias the yield. These results come from a single population, using a targeted panel where the exome already captures these genes.

Analysis by Dr Thibaut Benquey