The EPIGENE network: A French initiative to harmonize and improve the nationwide diagnosis of monogenic epilepsies

Background: The EPIGENE network was created in 2014 by four multidisciplinary teams composed of geneticists, pediatric neurologists and neurologists specialized in epileptology and neurophysiology. The ambition of the network was to harmonize and improve the diagnostic strategy of Mendelian epileptic disorders using next-generation sequencing, in France. Over the years, five additional centers have joined EPIGENE and the network has been working in close collaboration, since 2018, with the French reference center for rare epilepsies (CReER). Results: Since 2014, biannual meetings have led to the design of four successive versions of a monogenic epilepsy gene panel (PAGEM), increasing from 68 to 144 genes. A total of 4035 index cases with epileptic disorders have been analyzed with a diagnostic yield of 31% (n = 1265/4035). The top 10 genes, SCN1A, KCNQ2, STXBP1, SCN2A, SCN8A, PRRT2, PCDH19, KCNT1, SYNGAP1, and GRIN2A, account for one-sixth of patients and half of the diagnoses provided by the PAGEM. Conclusion: These results suggest that a gene-panel approach is an efficient first-tier test for the genetic diagnosis of Mendelian epileptic disorders. In a near future, French patients with drug-resistant epilepsies with seizure-onset in the first two-years of life can benefit from whole-genome sequencing (WGS), as a second line genetic screening with the implementation of the 2025 French Genomic Medicine Plan. The EPIGENE network has also promoted scientific collaborations on genetic epilepsies within CReER.

Automated summary

The EPIGENE network, consisting of geneticists, pediatric neurologists, and specialists in epileptology, aims to improve the diagnostic strategy for Mendelian epileptic disorders in France. Their gene panel approach has shown positive results, with a diagnostic yield of 31% for epileptic patients. Whole-genome sequencing is expected to be implemented as a second-line screening method in the near future, benefiting French patients with drug-resistant epilepsies.