The phenotypic spectrum of SCN8A encephalopathy

被引：240

作者：

Larsen, Jan ^{[1
,2
,18
]}

Carvill, Gemma L. ^{[3
]}

Gardella, Elena ^{[1
,18
]}

Kluger, Gerhard ^{[4
]}

Schmiedel, Gudrun ^{[7
]}

Barisic, Nina ^{[19
]}

Depienne, Christel ^{[8
,9
,10
]}

Brilstra, Eva ^{[5
,6
]}

Mang, Yuan ^{[2
]}

Nielsen, Jens Erik Klint ^{[11
]}

Kirkpatrick, Martin ^{[25
]}

Goudie, David ^{[26
]}

Goldman, Rebecca ^{[25
]}

Jaehn, Johanna A. ^{[29
]}

Jepsen, Birgit ^{[1
]}

Gill, Deepak ^{[30
]}

Doecker, Miriam ^{[27
,28
]}

Biskup, Saskia ^{[27
,28
]}

McMahon, Jacinta M. ^{[15
]}

Koeleman, Bobby ^{[5
,6
]}

Harris, Mandy ^{[31
]}

Braun, Kees ^{[5
,6
]}

de Kovel, Carolien G. F. ^{[12
]}

Marini, Carla ^{[24
]}

Specchio, Nicola ^{[22
,23
]}

Djemie, Tania ^{[20
,21
]}

Weckhuysen, Sarah ^{[20
,21
]}

Tommerup, Niels ^{[2
]}

Troncoso, Monica ^{[13
]}

Troncoso, Ledia ^{[13
]}

Bevot, Andrea ^{[17
]}

Wolff, Markus ^{[17
]}

Hjalgrim, Helle ^{[1
,18
]}

Guerrini, Renzo ^{[22
,23
]}

Scheffer, Ingrid E. ^{[14
,15
,16
]}

Mefford, Heather C. ^{[3
]}

Moller, Rikke S. ^{[1
,18
]}

机构：

[1] Univ Copenhagen, Panum Inst, Danish Epilepsy Ctr, DK-1168 Copenhagen, Denmark

[2] Univ Copenhagen, Panum Inst, ICMM, DK-1168 Copenhagen, Denmark

[3] Univ Washington, Dept Pediat, Div Med Genet, Seattle, WA 98195 USA

[4] Schon Klin Vogtareuth, Epilepsy Ctr Children & Adolescents, Clin Neuropediat & Neurorehabil, Vogtareuth, Germany

[5] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands

[6] Univ Med Ctr Utrecht, Dept Child Neurol, Utrecht, Netherlands

[7] Clin Children & Adolescents, Esslingen, Germany

[8] Univ Paris 06, Fac Med, Paris, France

[9] CNRS, INSERM, UMRS 975, UMR 725, Paris, France

[10] Univ Wurzburg, Inst Humangenet, Wurzburg, Germany

[11] Roskilde Hosp, Dept Clin Med, Sect Gynaecol Obstet & Paediat, Roskilde, Denmark

[12] UMC Utrecht, Utrecht, Netherlands

[13] Univ Chile, Child Neurol Serv, Hosp San Borja Arriaran, Santiago, Chile

[14] Univ Melbourne, Austin Hlth, Florey Inst Melbourne, Dept Med, Melbourne, Vic 3010, Australia

[15] Univ Melbourne, Austin Hlth, Epilepsy Res Ctr, Dept Med, Melbourne, Vic 3010, Australia

[16] Univ Melbourne, Royal Childrens Hosp, Dept Paediat, Melbourne, Vic 3010, Australia

[17] Univ Childrens Hosp, Dept Pediat Neurol, Tubingen, Germany

[18] Univ Southern Denmark, Inst Reg Hlth Serv Res, Fac Hlth Sci, Odense, Denmark

[19] Univ Hosp Ctr Zagreb, Dept Pediat, Zagreb, Croatia

[20] VIB, Dept Mol Genet, Neurogenet Grp, Antwerp, Belgium

[21] Univ Antwerp, Inst Born Bunge, Neurogenet Lab, Antwerp, Belgium

[22] Childrens Hosp A Meyer, Child Neurol Unit, Florence, Italy

[23] Univ Florence, I-50121 Florence, Italy

[24] Pediat Hosp Bambino Gesu, Child Neurol Unit, Rome, Italy

[25] Tayside Childrens Hosp, Dundee, Scotland

[26] Univ Dundee, Ninewells Hosp & Med Sch, Dundee DD1 9SY, Scotland

[27] DDD Study, Tubingen, Germany

[28] CeGaT GmbH Ctr Genom & Transcript, Tubingen, Germany

[29] Univ Kiel, Univ Med Ctr Schleswig Holstein, Kiel, Germany

[30] Childrens Hosp Westmead, TY Nelson Dept Neurol, Sydney, NSW, Australia

[31] Indiana Univ Hlth, Div Child Neurol, Dept Neurol, Indianapolis, IN USA

来源：

NEUROLOGY | 2015年 / 84卷 / 05期

基金：

英国惠康基金;

关键词：

DE-NOVO MUTATIONS; SODIUM-CHANNEL GENE; EPILEPTIC ENCEPHALOPATHY; EPILEPSIES; NA(V)1.6; SEIZURES; SCN1A;

D O I：

10.1212/WNL.0000000000001211

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Objective:SCN8A encodes the sodium channel voltage-gated 8-subunit (Na(v)1.6). 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.

引用

页码：480 / 489

页数：10

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