The objective of this study was to identify developmental trajectories of developmental/behavioral phenotypes and possibly their relationship to epilepsy and genotype by analyzing developmental and behavioral features collected prospectively and longitudinally in a cohort of patients with Dravet syndrome (DS). Thirty-four patients from seven Italian tertiary pediatric neurology centers were enrolled in the study. All patients were examined for the SCN1A gene mutation and prospectively assessed from the first years of life with repeated full clinical observations including neurological and developmental examinations. Subjects were found to follow three neurodevelopmental trajectories. In the first group (16 patients), an initial and usually mild decline was observed between the second and the third year of life, specifically concerning visuomotor abilities, later progressing towards global involvement of all abilities. The second group (12 patients) showed an earlier onset of global developmental impairment, progressing towards a generally worse outcome. The third group of only two patients ended up with a normal neurodevelopmental quotient, but with behavioral and linguistic problems. The remaining four patients were not classifiable due to a lack of critical assessments just before developmental decline. The neurodevelopmental trajectories described in this study suggest a differential contribution of neurobiological and genetic factors. The profile of the first group, which included the largest fraction of patients, suggests that in the initial phase of the disease, visuomotor defects might play a major role in determining developmental decline. Early diagnosis of milder cases with initial visuomotor impairment may therefore provide new tools for a more accurate habilitation strategy.

中文翻译：

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34 名 Dravet 综合征患者的多中心前瞻性纵向研究：生命前六年的神经心理发展

本研究的目的是通过分析在一组 Dravet 综合征 (DS) 患者中前瞻性和纵向收集的发育和行为特征，确定发育/行为表型的发育轨迹及其可能与癫痫和基因型的关系。来自七个意大利三级儿科神经病学中心的 34 名患者参加了这项研究。所有患者都接受了 SCN1A 基因突变的检查，并从出生后的最初几年进行了前瞻性评估，并重复进行了全面的临床观察，包括神经系统和发育检查。发现受试者遵循三个神经发育轨迹。在第一组（16 名患者）中，在生命的第二年和第三年之间观察到了最初的、通常是轻度的下降，特别是关于视觉运动能力，后来朝着所有能力的全球参与发展。第二组（12 名患者）表现出较早出现的全面发育障碍，并逐渐朝着更差的结果发展。第三组只有两名患者的神经发育商数正常，但存在行为和语言问题。由于在发育衰退之前缺乏关键评估，其余四名患者无法分类。本研究中描述的神经发育轨迹表明神经生物学和遗传因素的不同贡献。第一组患者的情况表明，在疾病的初始阶段，视觉运动缺陷可能在决定发育衰退中起主要作用。