APHP, Reference Centre for Rare Epilepsies, Department of Pediatric Neurology, Hôpital Necker-Enfants Malades, member of ERN EPICARE, Université de Paris, Paris, France; Laboratory of Translational Research for Neurological Disorders, INSERM UMR 1163, Imagine Institute, Université de Paris, Paris, France.
Department of Pediatrics, American Memorial Hospital, Reims, France.
Epilepsy Behav. 2022 Jan;126:108471. doi: 10.1016/j.yebeh.2021.108471. Epub 2021 Dec 13.
KCNB1 encephalopathy encompasses a broad phenotypic spectrum associating intellectual disability, behavioral disturbances, and epilepsies of various severity. Using standardized parental questionnaires, we aimed to capture the heterogeneity of the adaptive and behavioral features in a series of patients with KCNB1 pathogenic variants.
We included 25 patients with a KCNB1 encephalopathy, aged from 3.2 to 34.1 years (median = 10 years). Adaptive functioning was assessed in all patients using the French version of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) questionnaire. We screened global behavior with the Childhood Behavioral Check-List (CBCL, Achenbach) and autism spectrum disorder (ASD) with the Social Communication Questionnaire (SCQ). We used a cluster analysis to identify subgroups of adaptive profiles.
VABS-II questionnaire showed pathological adaptive behavior in all participants with a severity of adaptive deficiency ranging from mild in 8/20 to severe in 7/20. Eight out of 16 were at risk of Attention Problems at the CBCL and 13/18 were at risk of autism spectrum disorder (ASD). The adaptive behavior composite score significantly decreased with age (Spearman's Rho=-0.72, p<0.001) but not the equivalent ages, suggesting stagnation and slowing but no regression over time. The clustering analysis identified two subgroups of patients, one showing more severe adaptive behavior. The severity of the epilepsy phenotype predicted the severity of the behavioral profile with a sensitivity of 70% and a specificity of 90.9%.
This study confirms the deleterious consequences of early-onset epilepsy in addition to the impact of the gene dysfunction in patients with KCNB1 encephalopathy. ASD and attention disorders are frequent. Parental questionnaires should be considered as useful tools for early screening and care adaptation.
KCNB1 脑病具有广泛的表型谱，包括智力障碍、行为障碍和各种严重程度的癫痫。我们使用标准化的父母问卷，旨在捕捉一系列 KCNB1 致病性变异患者的适应性和行为特征的异质性。
我们纳入了 25 名 KCNB1 脑病患者，年龄 3.2 至 34.1 岁（中位数=10 岁）。使用法国版第二版 Vineland 适应行为量表（VABS-II）问卷评估所有患者的适应功能。我们使用儿童行为检查表（CBCL，Achenbach）筛查整体行为，使用社交沟通问卷（SCQ）筛查自闭症谱系障碍（ASD）。我们使用聚类分析来识别适应性特征的亚组。
VABS-II 问卷显示所有参与者均存在病理性适应行为，适应缺陷的严重程度从 8/20 的轻度到 7/20 的重度不等。16 人中的 8 人在 CBCL 中有注意力问题的风险，13/18 人有自闭症谱系障碍（ASD）的风险。适应性行为综合评分随年龄显著下降（Spearman's Rho=-0.72，p<0.001），但等效年龄没有下降，表明随着时间的推移适应性行为没有回归，但有停滞和减缓。聚类分析确定了两组患者，一组表现出更严重的适应性行为。癫痫表型的严重程度预测了行为特征的严重程度，其敏感性为 70%，特异性为 90.9%。
这项研究证实了早发性癫痫除了 KCNB1 脑病患者基因功能障碍的影响之外，还会产生有害后果。自闭症谱系障碍和注意力障碍很常见。父母问卷应被视为早期筛查和适应护理的有用工具。
