SCN2A-related neonatal-onset epilepsy responding significantly to lidocaine and lacosamide: A case report

Background SCN2A encodes the Nav1.2α subunit, a major component of voltage-gated sodium channels. Gain-of-function SCN2A variants are associated with self-limited neonatal/infantile epilepsy, infantile spasms, and developmental epileptic encephalopathy (DEE) whereas loss-of-function variants are associated with autistic spectrum disorder and intellectual disability. Mosaic SCN2A variants have also been reported in DEE. SCN2A -related disorders exhibit a broad phenotypic spectrum. Case presentation We report herein a full-term, male infant in whom neonatal-onset SCN2A -related epilepsy ( SCN2A : NM_021007.3: exon22: c.3983_3984AT>TG, p.[Asn1328Met], de novo , with a mosaic variant allele fraction [VAF] of 23%) appeared on postnatal day 1. Various types of frequent, brief, recurrent focal seizures developed at the age of 11 days, and status epilepticus developed at around the age of 1 month. In the early part of the clinical course, fosphenytoin was temporarily effective, but phenobarbital, levetiracetam, midazolam, pyridoxal phosphate, and folic acid were ineffective. Lidocaine produced a dramatic antiseizure effect, and lacosamide achieved sustained seizure control. Conclusion In neonatal-onset channelopathies, including SCN2A -related epilepsy, alternative sodium channel blockers, such as lidocaine or lacosamide, should be considered if fosphenytoin fails to control seizures. Given the phenotypic variability of SCN2A -related epilepsy, channelopathies can be difficult to diagnose early. To avoid a trial-and-error approach to seizure management, early genetic testing for epilepsy is warranted.