SCN2A mutation presenting with autism and epilepsy

Case presentation: The parents of a 38 months-old male patient seek neurological consultation for refractory seizures. He was previously treated with phenobarbital 4,7mg/kg/day and valproate 41mg/kg/day for febrile seizures that started at 30 months. The parents described generalized myoclonic seizures following staring. The patient presented seizures every 2 to 3 weeks when it was added clobazam 0,55mg/kg/day, oxcarbazepine 33,3mg/kg/day and cannabidiol 3,33mg/kg/day. He was diagnosed with autism spectrum disorder after presenting speech regression at the age of 18 months old. There was no known familiar history for epilepsy. No metabolic disorder was found, and the only significant prenatal finding was prematurity at gestational age of 34 weeks. He presented cryptorchidism. Electroencephalography recorded when he was 40 weeks-old was normal. The patient underwent a genetic panel for epilepsy, being discovered a heterozygous genetic variant of the SCN2A, chr2:165.313.721 G >A. The patient was seizure free for at least 3 months after oxcarbazepine suspension and dose adjustment of both valproate and phenobarbital.

Discussion: Mutations variants in SCN2A were proven to result in a wide spectrum of phenotypic disorders, ranging from benign familial neonatal-infantile seizures to more severe neurological conditions with delayed development (developmental and epileptic encephalopathy; intellectual disability, or autism with possible late-onset seizures). This case represents a new potentially pathogenic variant to the SCN2A gene presenting with epilepsy and autism. According to gene data banks, there is no evidence of it being a conserved benign variant. Additionally, it was once submitted as potentially pathogenic for development and epileptic encephalopathy, although it remains a variant of unknown significance (VUS). Since the gene in question encodes the voltage-gated sodium channel NaV1.2, there is a correlation to the response to treatment with sodium channel blockers.

Final comments: This case highlights the potentially deleterious effect of the mentioned variant and reflects the relevance of genetic tests to guide therapeutic choices. Some studies suggest that this gene is not only linked to epilepsy or autism but also to delay in neurological development as a whole. Furthermore, the genetic testing of both parents would help establish the pathogenic nature of the variant, differentiating a de novo mutation from a hereditary condition.

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Artikel online veröffentlicht:
18. September 2023