Dados do Trabalho

Título

NEW MUTATION IN SCN8A GENE ASSOCIATED SEVERE DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY TYPE 13: THE IMPORTANCE OF GENETIC TEST AND GENOTYPE-PHENOTYPE CORRELATION.

Apresentação do caso

Boy, 10 months, late premature infant. His parents aren’t consanguineous. He had recurrent and refractory spasm-like seizures, and neurodevelopmental regression started at 4 months. On physical examination, he had lack of visual and social interaction, microcephaly, central hypotonia, upper motor neuron syndrome and dyskinesias. He had seizure control with Levetiracetam for just one month. It was identified worsening of cortical and subcortical atrophy in two comparative his neuroimaging exams at 4 and 9 months. His electroencephalogram (EEG) was normal at 4 months. It were identified fragmented hypsiarrhythmia at 5 months and diffuse attenuation of brain activity at 7 months in serial EEG. Five variants of uncertain significance (VUS) were reported in his exome sequencing (ES): variants in the ABCA2 gene were identified in compound heterozygosity and in the CBL, HUWE1 and SCN8A genes in heterozygosity.

Discussão

The clinical features are compatible with Developmental and Epileptic Encephalopathy (DEE) type 13(MIM #614558) that is associated the pathogenic variants in SCN8A gene, autosomal dominant inheritance. The symptoms in DEE type 13 are epilepsy difficult to treat that worsened with Levetiracetam, developmental delay (DD), hypotonia e movement disorders. Initial EEG and neuroimaging exams may be normal with progressive changes, such as worsening brain atrophy. SCN8A gene encodes voltage-gated sodium channels and it is widely expressed in neurons of the central and peripheral nervous systems. Gain-of-function variants in the SCN8A gene cause severe DEE with early epilepsy. The variant c.409A>G:p.(Ile137Val) was identified in the patient and it was never described in the ClinVar, VarSome, AbraOM and Lovid databases. It’s concluded that variant c.409A>G is as highly likely to be pathogenic after genotype-phenotype correlation by clinical features, natural history of the disease and pathogenicity predictors LRT, MutationTaster, and SIFT classified this variant as deleterious, disease-causing, and harm-causing, respectively.

Comentários finais

We emphasize the importance of molecular tests in case of refractory epilepsies and DD with the aim of providing the best therapeutic choice and prognosis.

Referências (se houver)

- OMIM: DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 13; DEE13 (#614558). Disponível em: https://www.omim.org/entry/614558 Acesso em 22/07/2022
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Declaração de conflito de interesses de TODOS os autores

Não há conflito de interesses.