Authors :
Presenting Author: Emma Young, BSc (Hons) – University of Otago
Rebekah Harris, BSc – University of Melbourne; Nico Lieffering, BSc – University of Otago; Denis Nyaga, PhD – University of Otago; Michael Hildebrand, PHD – University of Melbourne; Ingrid Scheffer, PhD – University of Melbourne; Lynette Sadleir, MD, MBChB – University of Otago
Rationale:
SCN8A variants cause a spectrum of epilepsy phenotypes ranging from self-limited infantile epilepsy (SeLIE) to developmental and epileptic encephalopathy. SeLIE is a focal epilepsy with onset in developmentally normal infants between three and 20 months of age in which most children outgrow their seizures by three years of age. It is most commonly caused by variants in PRRT2, but rare cases are caused by SCN8A, KCNQ2 and SCN2A pathogenic variants. SCN8A-SeLIE is due to gain of function variants and although seizures are effectively treated with sodium channel blocking anti-seizure medications (ASMs), it is not clear how long ASM treatment is required. We report new individuals and families with SCN8A-SeLIE and review all previously published individuals to describe the natural history of seizures in this self-limited SCN8A epilepsy syndrome to help clinicians answer the question “When will seizures stop?”
Methods:
Individuals with SCN8A-epilepsy from an Australian-New Zealand epilepsy genetics research program were reviewed to identify those with SCN8A-related SeLIE. Following Interviews and review of medical records for each individual, the diagnosis of SeLIE was made using ILAE diagnostic criteria. Literature was searched to identify all SCN8A-SeLIE individuals with data on seizure progression. Results:
Nine New Zealand and Australian individuals with SCN8A-SeLIE from four families were identified (age at study: 2.5 to 66 years; median 25 years). Only 3/9 (33%) children stopped having seizures by three years of age; one child is only 2.5 years old and may have seizures in the future. Only 6/9 individuals had their last seizure between four and 23 years; however, five remain on ASM. Despite being drug-responsive, all six individuals failed multiple attempts (one to five) to wean ASMs. In the literature, 29 additional cases with SCN8A-SeLIE were identified. For the 22 individuals aged at least 10 years, only 9/22 (41%) had their last seizure prior to three years and 8/22 (36%) had seizures after 10 years.
Conclusions:
Our data highlights that over half of individuals with SCN8A-SeLIE continue to have seizures after age three years, and seizures may continue into late childhood. In contrast to children with SeLIE due to other aetiologies, many children with SCN8A-SeLIE have a more persistent, albeit very drug-responsive, form of epilepsy.
Funding:
Freemasons New Zealand, the Health Research Council of New Zealand, Cure Kids New Zealand, the Estate of Ernest Hyam Davis and the Tedd and Mollie Carr Endowment Trust and the National Health and Medical Research Council of Australia.