The spectrum of intermediate SCN 8A ‐related epilepsy

Johannesen, Katrine M., Gardella, Elena, Encinas, Alejandra C., Lehesjoki, Anna‐Elina, Linnankivi, Tarja, Petersen, Michael B., Lund, Ida C. B., Blichfeldt, Susanne, Miranda, Maria J., Pal, Deb K., Lascelles, Karine, Procopis, Peter, Orsini, Alessandro, Bonuccelli, Alice, Giacomini, Thea, Helbig, Ingo, Fenger, Christina D., Sisodiya, Sanjay M., Hernandez‐Hernandez, Laura, Krithika, S., Rumple, Melissa, Masnada, Silvia, Valente, Marialuisa, Cereda, Cristina, Giordano, Lucio, Accorsi, Patrizia, Bürki, Sarah E., Mancardi, Margherita, Korff, Christian, Guerrini, Renzo, Spiczak, Sarah, Hoffman‐Zacharska, Dorota, Mazurczak, Tomasz, Coppola, Antonietta, Buono, Salvatore, Vecchi, Marilena, Hammer, Michael F., Varesio, Costanza, Veggiotti, Pierangelo, Lal, Dennis, Brünger, Tobias, Zara, Federico, Striano, Pasquale, Rubboli, Guido and Møller, Rikke S. (2019) The spectrum of intermediate SCN 8A ‐related epilepsy. Epilepsia, 60 (5). pp. 830-844. ISSN 1528-1167

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Objective: Pathogenic variants in SCN 8A have been associated with a wide spectrum of epilepsy phenotypes, ranging from benign familial infantile seizures (BFIS ) to epileptic encephalopathies with variable severity. Furthermore, a few patients with intellectual disability (ID ) or movement disorders without epilepsy have been reported. The vast majority of the published SCN 8A patients suffer from severe developmental and epileptic encephalopathy (DEE ). In this study, we aimed to provide further insight on the spectrum of milder SCN 8A‐related epilepsies. Methods: A cohort of 1095 patients were screened using a next generation sequencing panel. Further patients were ascertained from a network of epilepsy genetics clinics. Patients with severe DEE and BFIS were excluded from the study. Results: We found 36 probands who presented with an SCN 8A‐related epilepsy and normal intellect (33%) or mild (61%) to moderate ID (6%). All patients presented with epilepsy between age 1.5 months and 7 years (mean = 13.6 months), and 58% of these became seizure‐free, two‐thirds on monotherapy. Neurological disturbances included ataxia (28%) and hypotonia (19%) as the most prominent features. Interictal electroencephalogram was normal in 41%. Several recurrent variants were observed, including Ile763Val, Val891Met, Gly1475Arg, Gly1483Lys, Phe1588Leu, Arg1617Gln, Ala1650Val/Thr, Arg1872Gln, and Asn1877Ser. Significance: With this study, we explore the electroclinical features of an intermediate SCN 8A‐related epilepsy with mild cognitive impairment, which is for the majority a treatable epilepsy.

Item Type: Journal Article
Keywords: epilepsy, epilepsy genetics, intellectual disability, SCN8A, voltage‐gated sodium channels
Faculty: Faculty of Science & Engineering
Depositing User: Lisa Blanshard
Date Deposited: 30 Jul 2020 14:09
Last Modified: 03 Feb 2022 10:45

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