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Título

NEONATAL EPILEPSY RELATED TO THE SCN2A GENE: A CASE REPORT

Apresentação do caso único

LMF, 4 months old, began experiencing focal seizures at 2 days of life, associated with intense crying and facial flushing. Initially treated with phenobarbital and levetiracetam without response. EEG identified abundant focal epileptiform discharges of spike and sharp wave, leading to the addition of topiramate and clobazam with continued unsatisfactory response. At 2 months, neurodevelopmental delay was noted, prompting the start of complementary genetic/metabolic investigation. Slight increases in glycine and threonine were found in amino acid chromatography, leading to the immediate initiation of protein restriction in the diet, combined with administration of sodium benzoate, folic acid, and pyridoxine. Despite supplementation, symptoms persisted. Oxcarbazepine was introduced, resulting in the progressive reduction of seizures until complete control of epileptic seizures and progressive developmental milestone gains. Exome analysis identified a pathogenic variant in the SCN2A gene, in heterozygosity, at position chr2:165.310.381, resulting in the amino acid substitution of methionine for isoleucine at codon 252.

Discussão

The SCN2A gene encodes a subunit of the Nav1.2 sodium channel, crucial for electrical conduction in neurons (1). Alteration in this gene can lead to dysfunction in brain electrical activity, causing a variety of epileptic manifestations that can begin in the neonatal period or result in later-onset epilepsies. Most cases of SCN2A-associated epilepsy are sporadic, resulting from de novo mutations, as in the case of the described patient (2). Prognosis depends on numerous factors, including the specific type of mutation, response to treatment, and the presence of associated comorbidities. Sodium channel blockers (SCBs) represent the first-line treatment for confirmed or suspected SCN2A-related epileptic encephalopathies (3). SCBs are often associated with clinically relevant seizure reduction or absence in children with early-onset epilepsies (<3 months), while other antiepileptic drugs are less effective (4).

Comentários finais

SCN2A-related neonatal encephalopathy is a complex condition requiring precise diagnosis and personalized treatment approaches. Due to the existing gain-of-function genetic mechanism, sodium channel blockers can improve seizure control and are considered the first-line treatment.

Referências

1. Zeng Q, Yang Y, Duan J, et al. SCN2A-Related Epilepsy: The Phenotypic Spectrum, Treatment and Prognosis. Front Mol Neurosci. 2022;15:809951. Published 2022 Mar 30. doi:10.3389/fnmol.2022.809951

2. Epifanio R, Giorda R, Merlano MC, et al. SCN2A Pathogenic Variants and Epilepsy: Heterogeneous Clinical, Genetic and Diagnostic Features. Brain Sci. 2021;12(1):18. Published 2021 Dec 24. doi:10.3390/brainsci12010018

3. Ogiwara I, Ito K, Sawaishi Y, et al. De novo mutations of voltage-gated sodium channel alphaII gene SCN2A in intractable epilepsies. Neurology. 2009;73(13):1046-1053. doi:10.1212/WNL.0b013e3181b9cebc

4. Wolff, et al. (2017). Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders. Brain, 140(5):1316-1336.

Palavras Chave

epilepsy; sodium channel blockers; SCN2-A