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The spectrum of intermediate SCN 8A ‐related epilepsy
Author(s) -
Johannesen Katrine M.,
Gardella Elena,
Encinas Alejandra C.,
Lehesjoki AnnaElina,
Linnankivi Tarja,
Petersen Michael B.,
Lund Ida Charlotte Bay,
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.,
HernandezHernandez Laura,
Krithika Sundararaman,
Rumple Melissa,
Masnada Silvia,
Valente Marialuisa,
Cereda Cristina,
Giordano Lucio,
Accorsi Patrizia,
Bürki Sarah E.,
Mancardi Margherita,
Korff Christian,
Guerrini Renzo,
Spiczak Sarah,
HoffmanZacharska 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,
Møller Rikke S.
Publication year - 2019
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.14705
Subject(s) - epilepsy , pediatrics , proband , hypotonia , ictal , childhood absence epilepsy , cohort , medicine , encephalopathy , west syndrome , psychology , psychiatry , mutation , genetics , biology , gene
Summary 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.