Dados do Trabalho

Título

A NOVEL DE NOVO SCN1A MISSENSE MUTATION IN A PATIENT WITH DRAVET SYNDROME

Apresentação do caso único

A 10-year-old male patient presented with epilepsy onset at 4 months of age, initially characterized by generalized clonic seizures associated with fever, which later progressed to afebrile hemiclonic seizures. He exhibited persistent delays in fine motor, language, and cognitive milestones as well as apendicular ataxia. Seizures occurred with weekly frequency, sometimes daily, leading to multiple hospitalizations for status epilepticus until the age of 7. The patient is currently on levetiracetam, clobazam, and topiramate treatment, which has effectively controlled the seizures. He was born via cesarean at 41 weeks of gestation to a 38-year-old mother following an uncomplicated pregnancy. The parents are non-consanguineous, and the two siblings of the patient are healthy. Complementary examinations, including EEG, revealed marked diffuse disorganization of baseline activity, with an increased presence of slow waves in the theta/delta range and monotonous bursts of slow waves, occasionally diffuse and more pronounced in the occipital regions. Brain MRI demonstrated mild diffuse atrophy. A molecular study utilizing next-generation sequencing (NGS) identified a heterozygous c.250T>C p.(Tyr84His) variant in exon 1 of the SCN1A gene, with no corresponding variants detected in the parents and none reported in existing databases.

Discussão

The SCN1A gene encodes the alpha subunit of the voltage-gated sodium channel Nav1.1, which is predominantly expressed in the central nervous system. Mutations in SCN1A are associated with a wide range of neurological disorders, including epilepsy. The phenotypic spectrum of these disorders spans from self-limited and pharmacoresponsive epilepsies, such as genetic epilepsy with febrile seizures plus (GEFS+), to more severe conditions like developmental and epileptic encephalopathies (DEEs). Dravet syndrome (DS) is the prototypic DEE with a mean age at seizure onset of 6 months. More than 80% of patients with DS have pathogenic variants in SCN1A, making it the epilepsy syndrome with the highest yield on genetic testing.

Comentários finais

The increasing number of reported variants in voltage-gated sodium channels is contributing to the development of new pharmacological applications through functional evaluation of these channels, ultimately enabling the selection of more precise antiepileptic drugs.

Referências

Scheffer IE, Nabbout R. SCN1A-related phenotypes: Epilepsy and beyond. Epilepsia. 2019 Dec;60 Suppl 3:S17-S24.
Brunklaus A, Brünger T, Feng T, et al. The gain of function SCN1A disorder spectrum: novel epilepsy phenotypes and therapeutic implications. Brain. 2022 Nov 21;145(11):3816-3831.

Fonte de Fomento (se houver)

Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (FAEPA)

Palavras Chave

SCN1A; epilepsy; DRAVET SYNDROME