The Danish Epilepsy Center Filadelfia, Dianalund, Denmark.
Institute for Regional Health Services Research, University of Southern Denmark, Odense, Denmark.
Epilepsia. 2018 Feb;59(2):389-402. doi: 10.1111/epi.13986. Epub 2018 Jan 8.
Pathogenic SLC6A1 variants were recently described in patients with myoclonic atonic epilepsy (MAE) and intellectual disability (ID). We set out to define the phenotypic spectrum in a larger cohort of SCL6A1-mutated patients.
We collected 24 SLC6A1 probands and 6 affected family members. Four previously published cases were included for further electroclinical description. In total, we reviewed the electroclinical data of 34 subjects.
Cognitive development was impaired in 33/34 (97%) subjects; 28/34 had mild to moderate ID, with language impairment being the most common feature. Epilepsy was diagnosed in 31/34 cases with mean onset at 3.7 years. Cognitive assessment before epilepsy onset was available in 24/31 subjects and was normal in 25% (6/24), and consistent with mild ID in 46% (11/24) or moderate ID in 17% (4/24). Two patients had speech delay only, and 1 had severe ID. After epilepsy onset, cognition deteriorated in 46% (11/24) of cases. The most common seizure types were absence, myoclonic, and atonic seizures. Sixteen cases fulfilled the diagnostic criteria for MAE. Seven further patients had different forms of generalized epilepsy and 2 had focal epilepsy. Twenty of 31 patients became seizure-free, with valproic acid being the most effective drug. There was no clear-cut correlation between seizure control and cognitive outcome. Electroencephalography (EEG) findings were available in 27/31 patients showing irregular bursts of diffuse 2.5-3.5 Hz spikes/polyspikes-and-slow waves in 25/31. Two patients developed an EEG pattern resembling electrical status epilepticus during sleep. Ataxia was observed in 7/34 cases. We describe 7 truncating and 18 missense variants, including 4 recurrent variants (Gly232Val, Ala288Val, Val342Met, and Gly362Arg).
Most patients carrying pathogenic SLC6A1 variants have an MAE phenotype with language delay and mild/moderate ID before epilepsy onset. However, ID alone or associated with focal epilepsy can also be observed.
最近在肌阵挛失神癫痫（MAE）和智力障碍（ID）患者中描述了致病性 SLC6A1 变体。我们着手在更大的 SCL6A1 突变患者队列中定义表型谱。
我们收集了 24 名 SLC6A1 先证者和 6 名受影响的家庭成员。纳入了另外 4 例先前发表的病例以进一步进行电临床描述。总共回顾了 34 名受试者的电临床数据。
34 名受试者中有 33 名（97%）认知发育受损；28 名有轻度至中度 ID，语言障碍是最常见的特征。31 例诊断为癫痫，平均发病年龄为 3.7 岁。在癫痫发作前可获得 24 名受试者的认知评估，其中 25%（6/24）正常，46%（11/24）为轻度 ID，17%（4/24）为中度 ID。有 2 名患者仅有言语延迟，1 名患者有严重 ID。癫痫发作后，24 名病例中有 46%（11/24）的认知恶化。最常见的发作类型是失神、肌阵挛和强直发作。16 例符合 MAE 的诊断标准。进一步有 7 例患者有不同形式的全面性癫痫，2 例有局灶性癫痫。31 例中有 20 例成为无癫痫发作，丙戊酸是最有效的药物。癫痫控制与认知结局之间没有明显的相关性。27/31 名患者可获得脑电图（EEG）发现，25/31 名患者显示不规则爆发的弥漫性 2.5-3.5 Hz 棘波/多棘波和慢波。2 名患者出现类似于睡眠中电癫痫持续状态的脑电图模式。34 名患者中有 7 名出现共济失调。我们描述了 7 种截断变异和 18 种错义变异，包括 4 种重复变异（Gly232Val、Ala288Val、Val342Met 和 Gly362Arg）。
大多数携带致病性 SLC6A1 变体的患者有 MAE 表型，在癫痫发作前有语言延迟和轻度/中度 ID。然而，也可以观察到单独的 ID 或伴有局灶性癫痫。
