Article (Scientific journals)
The phenotypic spectrum of SCN8A encephalopathy
Larsen, Jan; Carvill, Gemma L.; Gardella, Elena et al.
2015In Neurology, 84 (5), p. 480-489
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Keywords :
Genetics; Epilepsy; SCN8A
Abstract :
[en] Objective: SCN8A encodes the sodium channel voltage-gated α8-subunit (Nav1.6). SCN8A mutations have recently been associated with epilepsy and neurodevelopmental disorders. We aimed to delineate the phenotype associated with SCN8A mutations. Methods: We used high-throughput sequence analysis of the SCN8A gene in 683 patients with a range of epileptic encephalopathies. In addition, we ascertained cases with SCN8A mutations from other centers. A detailed clinical history was obtained together with a review of EEG and imaging data. Results: Seventeen patients with de novo heterozygous mutations of SCN8A were studied. Seizure onset occurred at a mean age of 5 months (range: 1 day to 18 months); in general, seizures were not triggered by fever. Fifteen of 17 patients had multiple seizure types including focal, tonic, clonic, myoclonic and absence seizures, and epileptic spasms; seizures were refractory to antiepileptic therapy. Development was normal in 12 patients and slowed after seizure onset, often with regression; 5 patients had delayed development from birth. All patients developed intellectual disability, ranging from mild to severe. Motor manifestations were prominent including hypotonia, dystonia, hyperreflexia, and ataxia. EEG findings comprised moderate to severe background slowing with focal or multifocal epileptiform discharges. Conclusion: SCN8A encephalopathy presents in infancy with multiple seizure types including focal seizures and spasms in some cases. Outcome is often poor and includes hypotonia and movement disorders. The majority of mutations arise de novo, although we observed a single case of somatic mosaicism in an unaffected parent.
Research center :
- Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group)
Luxembourg Centre for Systems Biomedicine (LCSB): Experimental Neurobiology (Balling Group)
Disciplines :
Genetics & genetic processes
Author, co-author :
Larsen, Jan
Carvill, Gemma L.
Gardella, Elena
Kluger, Gerhard
Schmiedel, Gudrun
Barisic, Nina
Depienne, Christel
Brilstra, Eva
Mang, Yuan
Nielsen, Jens E.K.
Kirkpatrick, Martin
Goudie, David
Goldman, Rebecca
Jähn, Johanna A.
Jepsen, Birgit
Gill, Deepak
Döcker, Miriam
Biskup, Saskia
McMahon, Jacinta M.
Koeleman, Bobby
Harris, Mandy
Braun, Kees
de Kovel, Carolien G.F.
Marini, Carla
Specchio, Nicola
Djémié, Tania
Weckhuysen, Sarah
Krause, Roland  ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
May, Patrick  ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Balling, Rudi ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Tommerup, Niels
Troncoso, Monica
Troncoso, Ledia
Bevot, Andrea
Wolff, Markus
Hjalgrim, Helle
Guerrini, Renzo
Scheffer, Ingrid E.
Mefford, Heather C.
Møller, Rikke S.
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Title :
The phenotypic spectrum of SCN8A encephalopathy
Publication date :
03 February 2015
Journal title :
Publisher :
Lippincott Williams & Wilkins, Hagerstown, United States - Maryland
Volume :
Issue :
Pages :
Peer reviewed :
Peer Reviewed verified by ORBi
Focus Area :
Systems Biomedicine
Available on ORBilu :
since 01 April 2016


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