The genetic architecture of the pediatric epilepsies

ICNC2024
Symposia: The Impact of Genetics In The Care of Patients With Rare Pediatric Epilepsies: Past, Present Future

The genetic architecture of the pediatric epilepsies
Laura Swanson

The widespread implementation of high-throughput DNA sequencing has revolutionized our understanding of the genetic basis of the pediatric epilepsies, especially the Developmental and epileptic encephalopathies (DEEs). We now know that ~50% of patients have a genetic diagnosis, and that over 300 genes have been identified. In most high-income countries, gene panel testing is available for all new onset epilepsy cases in infants, and young children. Meanwhile in low-middle income countries, these tests are more difficult to access, though several groups are developing targeted-strategies to address these inequities and restrictions to access. A genetic diagnosis is also changing the way we treat and care for patients with DEEs, and there is an exciting move towards precision therapies. At present, this primarily involves avoiding specific anti-seizure medications (ASMs), such as sodium channel blockers in SCN1A-related epilepsies, or recommending other ASMs, such as sodium channel blockers in SCN8A-related epilepsies. However, there is now also much enthusiasm from pharmaceutical and biotech companies in rare disease and gene-targeting approaches to curing DEEs. There are now several clinical trials, and these approaches have the ability to transform lives, by treating the cause, rather than the symptoms of seizures. Finally, the remaining 50% of patients do not have a known genetic cause and in this symposium, we discuss the numerous approaches to finding answers for patients.

Other Lectures in this symposium
Diagnosing Genetic Epilepsy in a Resource-Constrained Setting – the South African experience

Mosaic variants detectable in blood extend the clinico-genetic spectrum of GLI3-related Hypothalamic Hamartoma

Epigenetic approaches to epilepsy diagnosis