The phenotypic spectrum of SCN8A encephalopathy
The phenotypic spectrum of SCN8A encephalopathy
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DOI：
10.1212/wnl.0000000000001211
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发表时间：
2015-02-03
期刊：
影响因子：
9.9
通讯作者：
Moller, Rikke S.
中科院分区：
文献类型：
--
作者：
Larsen, Jan;Carvill, Gemma L.;Moller, Rikke S.
目的：SCN 8A编码钠通道电压门控性8亚基（Na（v）1.6）。SCN 8A突变最近与癫痫和神经发育障碍有关。我们的目的是描绘与SCN 8A mutations.Methods相关的表型：我们使用了高通量序列分析的SCN 8A基因在683例癫痫性脑病患者的范围。此外，我们确定了其他中心的SCN 8A突变病例。一个详细的临床病史一起获得审查EEG和影像学data.Results：17例患者与新生杂合突变的SCN 8A进行了研究。癫痫发作发生的平均年龄为5个月（范围：1天至18个月）;一般来说，癫痫发作不是由发热引发的。17例患者中有15例有多种癫痫发作类型，包括局灶性、强直性、阵挛性、肌阵挛性和失神发作以及癫痫痉挛;癫痫发作对抗癫痫治疗无效。12例患者的发育正常，癫痫发作后发育减慢，通常伴有退化; 5例患者从出生起发育延迟。所有患者均出现轻度至重度智力残疾。运动表现突出，包括张力减退、肌张力障碍、反射亢进和共济失调。EEG表现为中度至重度背景减慢伴局灶性或多灶性癫痫样放电。结论：SCN 8A脑病在婴儿期表现为多种癫痫发作类型，包括局灶性发作和部分病例的痉挛。结果通常很差，包括张力减退和运动障碍。大多数的突变出现从头，虽然我们观察到一个单一的情况下，体细胞镶嵌在一个未受影响的父母。
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.