A pathogenic variant in can result in a spectrum of phenotypes, including Dravet syndrome (DS) and genetic epilepsy with febrile seizures plus (GEFS + ) syndrome. Dravet syndrome (DS) is associated with refractory seizures, developmental delay, intellectual disability (ID), motor impairment, and challenging behavior(1,2). GEFS + is a less severe phenotype in which cognition is often normal and seizures are less severe. Challenging behavior largely affects quality of life of patients and their families. This study describes the profile and course of the behavioral phenotype in patients with -related epilepsy syndromes, explores correlations between behavioral difficulties and potential risk factors. Data were collected from questionnaires, medical records, and semi-structured interviews. Behavior difficulties were measured using the Adult/Child Behavior Checklist (C/ABCL) and Adult self-report (ASR). Other questionnaires included the Pediatric Quality of Life Inventory (PedsQL), the Functional Mobility Scale (FMS) and the Sleep Behavior Questionnaire by Simonds & Parraga (SQ-SP). To determine differences in behavioral difficulties longitudinally, paired T-tests were used. Pearson correlation and Spearman rank test were used in correlation analyses and multivariable regression analyses were employed to identify potential risk factors. A cohort of 147 participants, including 107 participants with DS and 40 with genetic epilepsy with febrile seizures plus (GEFS + ), was evaluated. Forty-six DS participants (43.0 %) and three GEFS + participants (7.5 %) showed behavioral problems in the clinical range on the A/CBCL total problems scale. The behavioral profile in DS exists out of withdrawn behavior, aggressive behavior, and attention problems. In DS patients, sleep disturbances (β = 1.15, p < 0.001) and a lower age (β = -0.21, p = 0.001) were significantly associated with behavioral difficulties. Between 2015 and 2022, behavioral difficulties significantly decreased with age (t = -2.24, CI = -6.10 – −0.15, p = 0.04) in DS participants aging from adolescence into adulthood. A decrease in intellectual functioning (β = 3.37, p = 0.02) and using less antiseizure medications in 2022 than in 2015, (β = -1.96, p = 0.04), were identified as possible risk factors for developing (more) behavioral difficulties. These findings suggest that, in addition to epilepsy, behavioral difficulties are a core feature of the DS phenotype. Behavioral problems require personalized management and treatment strategies. Further research is needed to identify effective interventions.

中文翻译：

---

了解 SCN1A 相关癫痫综合征的神经发育轨迹和行为特征

致病性变异可导致一系列表型，包括 Dravet 综合征 (DS) 和遗传性癫痫伴热性惊厥加 (GEFS + ) 综合征。 Dravet 综合征 (DS) 与难治性癫痫发作、发育迟缓、智力障碍 (ID)、运动障碍和挑战性行为相关 (1,2)。 GEFS + 是一种不太严重的表型，其中认知通常正常并且癫痫发作不太严重。挑战性行为很大程度上影响患者及其家人的生活质量。本研究描述了癫痫相关综合征患者行为表型的概况和过程，探讨了行为困难与潜在危险因素之间的相关性。数据来自问卷、病历和半结构化访谈。使用成人/儿童行为检查表（C/ABCL）和成人自我报告（ASR）来测量行为困难。其他问卷包括儿科生活质量量表 (PedsQL)、功能活动量表 (FMS) 和 Simonds & Parraga 的睡眠行为问卷 (SQ-SP)。为了纵向确定行为困难的差异，使用了配对 T 检验。采用Pearson相关和Spearman等级检验进行相关分析，并采用多变量回归分析来识别潜在的危险因素。对 147 名参与者组成的队列进行了评估，其中 107 名患有 DS 的参与者和 40 名患有遗传性癫痫伴热性惊厥附加 (GEFS + ) 的参与者。 46 名 DS 参与者 (43.0 %) 和 3 名 GEFS + 参与者 (7.5 %) 在 A/CBCL 总问题量表中表现出临床范围内的行为问题。 DS 中的行为特征包括孤僻行为、攻击性行为和注意力问题。在 DS 患者中，睡眠障碍（β = 1.15，p < 0.001）和较低年龄（β = -0.21，p = 0.001）与行为困难显着相关。 2015 年至 2022 年间，DS 参与者从青春期进入成年后，行为困难随着年龄的增长而显着减少（t = -2.24，CI = -6.10 – -0.15，p = 0.04）。与 2015 年相比，2022 年智力功能下降（β = 3.37，p = 0.02）和使用较少的抗癫痫药物（β = -1.96，p = 0.04）被认为是发生（更多）行为困难的可能风险因素。这些发现表明，除了癫痫之外，行为困难也是 DS 表型的核心特征。行为问题需要个性化的管理和治疗策略。需要进一步研究以确定有效的干预措施。