Genetic and clinical features of SCN8A developmental and epileptic encephalopathy

• Published in: Epilepsy research 2019-12, Vol.158, p.106222-106222, Article 106222
• Main Authors: Kim, Hyo Jeong, Yang, Donghwa, Kim, Se Hee, Kim, Borahm, Kim, Heung Dong, Lee, Joon Soo, Choi, Jong Rak, Lee, Seung-Tae, Kang, Hoon-Chul
• Format: Article
• Language: English
• Subjects: Child; Developmental and epileptic encephalopathy; Epilepsy - drug therapy; Epilepsy - genetics; Female; Humans; Male; Mutation - genetics; NAV1.6 Voltage-Gated Sodium Channel - genetics; Phenotype; SCN8A; Seizures - drug therapy; Seizures - genetics; Sodium channel blockers; Sodium Channel Blockers - pharmacology; Young Adult
• ISSN: 0920-1211; 1872-6844
• DOI: 10.1016/j.eplepsyres.2019.106222

•De novo missense mutations cause SCN8A encephalopathy.•Intractable seizures including spasms and focal seizures are present in 6/9(66.7%).•Sodium channel blockers are effective in 7/8(87.5%). We aim to delineate the genetic and clinical features of SCN8A developmental and epileptic encephalopathy. Nine patients with SCN8A developmental and epileptic encephalopathy were included in this study. Genetic and clinical features and effectiveness of sodium channel blockers were assessed in patients who were confirmed with SCN8A mutations. The onset of seizures ranged from the neonatal period to 18 months of age. Seizure types were diverse and predominantly involved focal seizures or spasms. The most common initial epilepsy syndrome was West syndrome in four patients, followed by neonatal-onset focal seizures in three patients and unclassified focal epilepsy in two patients. Electroencephalograms (EEGs) showed slow and disorganized background and epileptiform abnormalities with occipital predominance. Six patients presented intractable seizures including one patient with recurrent nonconvulsive status epilepticus. Sodium channel blockers were effective in seven patients among eight patients given them. All patients showed developmental delay or regression. Severe hypotonia or ataxia was also presented in some patients. Microcephaly was also characteristic. De novo missense mutations in SCN8A were found in the inactivation gate, C-terminal, loop 2, and transmembrane segments (S1, 4, 5, and 6). There was no correlation between the location of the mutation in the protein and phenotype or response to sodium channel blockers. SCN8A developmental and epileptic encephalopathy presents intractable seizures including spasms, focal seizures, neonatal status epilepticus, and nonconvulsive status epilepticus. Sodium channel blockers were effective irrelevant to the location of the mutation in the protein.