Abstract

The impact of gene-related early infancy onset epilepsies in cognitive development can be potentially devastating. Here we report two cases of SCN8A-related epilepsy that highlight the neuropsychological heterogeneity seen with differing de-novo pathogenic variants. Case 1 is a 6-year-old right-handed girl who presented with SCN8A-developmental and epileptic encephalopathy (SCN8A-DEE) and a missense pathogenic variant (c.802A > C), not previously documented in the literature. Her history includes speech and motor delay, with focal motor seizures starting at 4-months. Early EEG showed bilateral centroparietal epileptiform discharges. She shows motor and language delays and prominent motor tics. Testing documented Intellectual Disability (ID) (Mild) with widespread neuropsychological deficits (i.e., academics, attention/executive functions, memory, visual-spatial skills, fine motor, language). Case 2 is an 8-year-old right-handed girl who presented with SCN8A-related epilepsy with c.5630A > G pathogenic variant with seizure onset at 5-months. Her initial EEG showed right occipital spikes. She shows low average intellect and average academics, but evaluation documented attention deficits, fine motor delays, and behavioral issues in addition to tics; she was diagnosed with Attention-Deficit/Hyperactivity Disorder, Oppositional Defiant Disorder, Obsessive Compulsive Disorder, and Tourette’s. These cases expand limited knowledge regarding neuropsychological functioning of children with SCN8A-related epilepsy with unique de-novo pathogenic variants. While SCN8A-DEE is clearly associated with ID, other pathogenic variants may show better preserved intellect, despite other neuropsychological and behavioral concerns.

摘要

基因相关的婴儿早期发作性癫痫对认知发展的影响可能是毁灭性的。在这里，我们报告了两例与 SCN8A 相关的癫痫病例，这些病例突出了不同的新发致病变异所见的神经心理异质性。病例 1 是一名 6 岁的右利手女孩，她出现 SCN8A 发育性和癫痫性脑病 (SCN8A-DEE) 和错义致病变异 (c.802A > C)，以前没有文献记载。她的病史包括言语和运动延迟，从 4 个月开始出现局灶性运动癫痫发作。早期脑电图显示双侧中央顶叶癫痫样放电。她表现出运动和语言迟缓以及明显的运动抽动。测试记录了智力障碍 (ID)（轻度），伴有广泛的神经心理缺陷（即学术、注意力/执行功能、记忆力、视觉空间技能、精细动作、语言）。病例 2 是一名 8 岁右利手女孩，她在 5 个月时出现 SCN8A 相关性癫痫，具有 c.5630A > G 致病性变异，癫痫发作。她最初的脑电图显示右侧枕骨尖峰。她的平均智力和学术水平都很低，但评估记录了除了抽动之外还有注意力缺陷、精细运动迟缓和行为问题；她被诊断出患有注意力缺陷/多动障碍、对立违抗障碍、强迫症和图雷特氏症。这些病例扩展了对具有独特的新发致病变异的 SCN8A 相关癫痫患儿的神经心理功能的有限知识。虽然 SCN8A-DEE 明显与 ID 相关，但其他致病变异可能显示出更好的智力保留，