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Título

SNC8A ARG1872GLN MUTATION PRESENTING WITH EPILEPTIC ENCEPHALOPATHY

Apresentação do caso único

Case presentation: We present a 17 year-old female patient referred to our tertiary institution to undergo intra-hospitalar epilepsy investigation. First seizure was at 3-4 weeks of age. Episodes begin with right ocular and cephalic versions followed by generalized tonic extension progressing with clonic features. Whenever she is even mildly febrile, her seizures decompensate and intra-hospitalar treatment is required.
Parents described development regression with each seizure. She walked at 23 months-old and could only speak a few words at 4 year-old. She currently maintains marked language delay, being lettered and speaking short phrases.
She currently presents 2-3 seizures per month and is treated with lamotrigine 400mg/day, topiramate 100mg/day and clobazam 25mg/day. Previous medication includes phenobarbital, phenytoin, valproic acid, levetiracetam and carbamazepine. She presents aggressive behavior and self harm, with poor control treating with risperidone, aripiprazole and clozapine.
Family history includes 2 second degree relatives with childhood seizures and a third degree relative with autism. There is no known consanguinity and her 24 year-old sister is asymptomatic.
MRI investigation is normal, apart of questionable left hippocampus atrophy. Continuous EEG monitoring shows mainly focal epileptic zones at the left posterior region, although irritative epileptic zones are evident bilaterally. The three monitored seizures seemed to start focally at the left hemisphere, beginning varying from temporal to occipital regions. Broad epilepsy genetic panel showed SNC8A mutation Arg1872Gln, classified as pathogenic.

Discussão

Discussion: SCN8A encodes sodium voltage-dependent channels and presents various mutations causing encephalopathic epilepsy. Notability refractory seizures are identified, and neurodevelopment is usually delayed or presents regression with seizures. The particular variant shown in our patient was described in 11 other patients, being confirmed as a de novo mutation in 3 of those cases. It is considered to have an autosomal dominant inheritance, with the possibility of parents having a mosaic pattern presentation.

Comentários finais

Final comments: Data from literature shows that mutations in SCN8A represent 1% of all epileptic encephalopathies, and counterintuitively could respond to sodium channel blockers. The presented case shows a relatively rare mutation variant at said gene, that represents a chance to individualize treatment and to understand prognosis.

Referências

https://www.ncbi.nlm.nih.gov/clinvar/variation/253297/?oq=253297&m=NM_001330260.2(SCN8A):c.5615G%3EA%20(p.Arg1872Gln)#new-submission-germline
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216308/pdf/nihms-1059430.pdf
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4336074/pdf/NEUROLOGY2014595553.pdf
https://www.omim.org/entry/614558?search=SCN8A&highlight=scn8a
https://www.ncbi.nlm.nih.gov/clinvar/variation/253297/?oq=253297&m=NM_001330260.2(SCN8A):c.5615G%3EA%20(p.Arg1872Gln)#new-submission-germline

Palavras Chave

Neurogenetics; Epileptic encephalopathy; sodium channel