The spectrum of intermediate SCN8A-related epilepsy

Katrine M. Johannesen; Elena Gardella; Alejandra C. Encinas; Anna Elina Lehesjoki; Tarja Linnankivi; Michael B. Petersen; Ida Charlotte Bay Lund; Susanne Blichfeldt; Maria J. Miranda; Deb K. Pal; Karine Lascelles; Peter Procopis; Alessandro Orsini; Alice Bonuccelli; Thea Giacomini; Ingo Helbig; Christina D. Fenger; Sanjay M. Sisodiya; Laura Hernandez-Hernandez; Sundararaman Krithika; Melissa Rumple; Silvia Masnada; Marialuisa Valente; Cristina Cereda; Lucio Giordano; Patrizia Accorsi; Sarah E. Bürki; Margherita Mancardi; Christian Korff; Renzo Guerrini; Sarah von Spiczak; Dorota Hoffman-Zacharska; Tomasz Mazurczak; Antonietta Coppola; Salvatore Buono; Marilena Vecchi; Michael F. Hammer; Costanza Varesio; Pierangelo Veggiotti; Dennis Lal; Tobias Brünger; Federico Zara; Pasquale Striano; Guido Rubboli; Rikke S. Møller

doi:10.1111/epi.14705

The spectrum of intermediate SCN8A-related epilepsy

Katrine M. Johannesen, Elena Gardella, Alejandra C. Encinas, Anna Elina Lehesjoki, Tarja Linnankivi, Michael B. Petersen, Ida Charlotte Bay Lund, Susanne Blichfeldt, Maria J. Miranda, Deb K. Pal, Karine Lascelles, Peter Procopis, Alessandro Orsini, Alice Bonuccelli, Thea Giacomini, Ingo Helbig, Christina D. Fenger, Sanjay M. Sisodiya, Laura Hernandez-Hernandez, Sundararaman KrithikaMelissa Rumple, Silvia Masnada, Marialuisa Valente, Cristina Cereda, Lucio Giordano, Patrizia Accorsi, Sarah E. Bürki, Margherita Mancardi, Christian Korff, Renzo Guerrini, Sarah von Spiczak, Dorota Hoffman-Zacharska, Tomasz Mazurczak, Antonietta Coppola, Salvatore Buono, Marilena Vecchi, Michael F. Hammer, Costanza Varesio, Pierangelo Veggiotti, Dennis Lal, Tobias Brünger, Federico Zara, Pasquale Striano, Guido Rubboli, Rikke S. Møller

Arizona Research Labs

Research output: Contribution to journal › Article › peer-review

67 Scopus citations

Abstract

Objective: Pathogenic variants in SCN8A 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 SCN8A patients suffer from severe developmental and epileptic encephalopathy (DEE). In this study, we aimed to provide further insight on the spectrum of milder SCN8A-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 SCN8A-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 SCN8A-related epilepsy with mild cognitive impairment, which is for the majority a treatable epilepsy.

Original language	English (US)
Pages (from-to)	830-844
Number of pages	15
Journal	Epilepsia
Volume	60
Issue number	5
DOIs	https://doi.org/10.1111/epi.14705
State	Published - May 2019

Keywords

SCN8A
epilepsy
epilepsy genetics
intellectual disability
voltage-gated sodium channels

ASJC Scopus subject areas

Neurology
Clinical Neurology

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10.1111/epi.14705

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Johannesen, K. M., Gardella, E., Encinas, A. C., Lehesjoki, A. E., Linnankivi, T., Petersen, M. B., Lund, I. C. B., Blichfeldt, S., Miranda, M. J., Pal, D. K., Lascelles, K., Procopis, P., Orsini, A., Bonuccelli, A., Giacomini, T., Helbig, I., Fenger, C. D., Sisodiya, S. M., Hernandez-Hernandez, L., ... Møller, R. S. (2019). The spectrum of intermediate SCN8A-related epilepsy. Epilepsia, 60(5), 830-844. https://doi.org/10.1111/epi.14705

Johannesen, KM, Gardella, E, Encinas, AC, Lehesjoki, AE, Linnankivi, T, Petersen, MB, Lund, ICB, Blichfeldt, S, Miranda, MJ, Pal, DK, Lascelles, K, Procopis, P, Orsini, A, Bonuccelli, A, Giacomini, T, Helbig, I, Fenger, CD, Sisodiya, SM, Hernandez-Hernandez, L, Krithika, S, Rumple, M, Masnada, S, Valente, M, Cereda, C, Giordano, L, Accorsi, P, Bürki, SE, Mancardi, M, Korff, C, Guerrini, R, von Spiczak, S, Hoffman-Zacharska, D, Mazurczak, T, Coppola, A, Buono, S, Vecchi, M, Hammer, MF, Varesio, C, Veggiotti, P, Lal, D, Brünger, T, Zara, F, Striano, P, Rubboli, G & Møller, RS 2019, 'The spectrum of intermediate SCN8A-related epilepsy', Epilepsia, vol. 60, no. 5, pp. 830-844. https://doi.org/10.1111/epi.14705

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title = "The spectrum of intermediate SCN8A-related epilepsy",

abstract = "Objective: Pathogenic variants in SCN8A 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 SCN8A patients suffer from severe developmental and epileptic encephalopathy (DEE). In this study, we aimed to provide further insight on the spectrum of milder SCN8A-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 SCN8A-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 SCN8A-related epilepsy with mild cognitive impairment, which is for the majority a treatable epilepsy.",

keywords = "SCN8A, epilepsy, epilepsy genetics, intellectual disability, voltage-gated sodium channels",

author = "Johannesen, {Katrine M.} and Elena Gardella and Encinas, {Alejandra C.} and Lehesjoki, {Anna Elina} and Tarja Linnankivi and Petersen, {Michael B.} and Lund, {Ida Charlotte Bay} and Susanne Blichfeldt and Miranda, {Maria J.} and Pal, {Deb K.} and Karine Lascelles and Peter Procopis and Alessandro Orsini and Alice Bonuccelli and Thea Giacomini and Ingo Helbig and Fenger, {Christina D.} and Sisodiya, {Sanjay M.} and Laura Hernandez-Hernandez and Sundararaman Krithika and Melissa Rumple and Silvia Masnada and Marialuisa Valente and Cristina Cereda and Lucio Giordano and Patrizia Accorsi and B{\"u}rki, {Sarah E.} and Margherita Mancardi and Christian Korff and Renzo Guerrini and {von Spiczak}, Sarah and Dorota Hoffman-Zacharska and Tomasz Mazurczak and Antonietta Coppola and Salvatore Buono and Marilena Vecchi and Hammer, {Michael F.} and Costanza Varesio and Pierangelo Veggiotti and Dennis Lal and Tobias Br{\"u}nger and Federico Zara and Pasquale Striano and Guido Rubboli and M{\o}ller, {Rikke S.}",

note = "Publisher Copyright: Wiley Periodicals, Inc. {\textcopyright} 2019 International League Against Epilepsy",

year = "2019",

month = may,

doi = "10.1111/epi.14705",

language = "English (US)",

volume = "60",

pages = "830--844",

journal = "Epilepsia",

issn = "0013-9580",

publisher = "Wiley-Blackwell",

number = "5",

}

TY - JOUR

T1 - The spectrum of intermediate SCN8A-related epilepsy

AU - Johannesen, Katrine M.

AU - Gardella, Elena

AU - Encinas, Alejandra C.

AU - Lehesjoki, Anna Elina

AU - Linnankivi, Tarja

AU - Petersen, Michael B.

AU - Lund, Ida Charlotte Bay

AU - Blichfeldt, Susanne

AU - Miranda, Maria J.

AU - Pal, Deb K.

AU - Lascelles, Karine

AU - Procopis, Peter

AU - Orsini, Alessandro

AU - Bonuccelli, Alice

AU - Giacomini, Thea

AU - Helbig, Ingo

AU - Fenger, Christina D.

AU - Sisodiya, Sanjay M.

AU - Hernandez-Hernandez, Laura

AU - Krithika, Sundararaman

AU - Rumple, Melissa

AU - Masnada, Silvia

AU - Valente, Marialuisa

AU - Cereda, Cristina

AU - Giordano, Lucio

AU - Accorsi, Patrizia

AU - Bürki, Sarah E.

AU - Mancardi, Margherita

AU - Korff, Christian

AU - Guerrini, Renzo

AU - von Spiczak, Sarah

AU - Hoffman-Zacharska, Dorota

AU - Mazurczak, Tomasz

AU - Coppola, Antonietta

AU - Buono, Salvatore

AU - Vecchi, Marilena

AU - Hammer, Michael F.

AU - Varesio, Costanza

AU - Veggiotti, Pierangelo

AU - Lal, Dennis

AU - Brünger, Tobias

AU - Zara, Federico

AU - Striano, Pasquale

AU - Rubboli, Guido

AU - Møller, Rikke S.

PY - 2019/5

Y1 - 2019/5

N2 - Objective: Pathogenic variants in SCN8A 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 SCN8A patients suffer from severe developmental and epileptic encephalopathy (DEE). In this study, we aimed to provide further insight on the spectrum of milder SCN8A-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 SCN8A-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 SCN8A-related epilepsy with mild cognitive impairment, which is for the majority a treatable epilepsy.

AB - Objective: Pathogenic variants in SCN8A 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 SCN8A patients suffer from severe developmental and epileptic encephalopathy (DEE). In this study, we aimed to provide further insight on the spectrum of milder SCN8A-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 SCN8A-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 SCN8A-related epilepsy with mild cognitive impairment, which is for the majority a treatable epilepsy.

KW - SCN8A

KW - epilepsy

KW - epilepsy genetics

KW - intellectual disability

KW - voltage-gated sodium channels

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U2 - 10.1111/epi.14705

DO - 10.1111/epi.14705

M3 - Article

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AN - SCOPUS:85064156848

SN - 0013-9580

VL - 60

SP - 830

EP - 844

JO - Epilepsia

JF - Epilepsia

IS - 5

ER -

The spectrum of intermediate SCN8A-related epilepsy

Abstract

Keywords

ASJC Scopus subject areas

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