Background

Epilepsy is highly prevalent in children with Angelman syndrome (AS), and its detailed characterization and relationship to the genotype (deletion vs nondeletion) is important both for medical practice and for clinical trial design.

Methods and Materials

We retrospectively analyzed the main clinical features of epilepsy in 265 children with AS who were enrolled in the AS Natural History Study, a multicenter, observational study conducted at six centers in the United States. Participants were prospectively followed up and classified by genotype.

Results

Epilepsy was reported in a greater proportion of individuals with a deletion than a nondeletion genotype (171 of 187 [91%] vs. 48 of 78 [61%], P < 0.001). Compared with participants with a nondeletion genotype, those with deletions were younger at the time of the first seizure (age: median [95% confidence interval]: 24 [21-24] months vs. 57 [36-85] months, P < 0.001) and had a higher prevalence of generalized motor seizures. Hospitalization following a seizure was reported in more children with a deletion than a nondeletion genotype (92 of 171 [54%] vs. 17 of 48 [36%], P = 0.04). The overall prevalence of absence seizures was not significantly different between genotype groups. Forty-six percent (102/219) of the individuals reporting epilepsy were diagnosed with AS concurrently or after their first seizure.

Conclusions

Significant differences exist in the clinical expression of epilepsy in AS according to the underlying genotype, with earlier age of onset and more severe epilepsy in individuals with AS due to a chromosome 15 deletion.

中文翻译：

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Angelman综合征患儿癫痫的临床特征

背景

癫痫在患有 Angelman 综合征 (AS) 的儿童中非常普遍，其详细特征和与基因型的关系（缺失与非缺失）对于医疗实践和临床试验设计都很重要。

方法和材料

我们回顾性分析了参加 AS 自然史研究的 265 名 AS 儿童的癫痫主要临床特征，这是一项在美国六个中心进行的多中心观察性研究。参与者被前瞻性随访并按基因型分类。

结果

与非缺失基因型相比，缺失基因型个体中报告癫痫的比例更高（187 人中的 171 人 [91%] vs. 78 人中的 48 人 [61%]，P  < 0.001）。与具有非缺失基因型的参与者相比，缺失基因型的参与者在第一次癫痫发作时更年轻（年龄：中位数 [95% 置信区间]：24 [21-24] 个月 vs. 57 [36-85] 个月，P  < 0.001）并且全身性运动癫痫发作的患病率更高。据报道，与非缺失基因型相比，缺失基因型的儿童在癫痫发作后住院的人数更多（171 名中的 92 名 [54%] 对 48 名中的 17 名 [36%]，P = 0.04)。失神发作的总体患病率在基因型组之间没有显着差异。46% (102/219) 报告癫痫的个体在第一次癫痫发作的同时或之后被诊断出患有 AS。

结论

根据潜在基因型，AS 中癫痫的临床表现存在显着差异，由于 15 号染色体缺失，AS 个体的发病年龄更早，癫痫更严重。