We are grateful for the opportunity to respond to the letter: Do all individuals with Dravet syndrome have intellectual disability? from Reilly and colleagues.¹

The authors of the International League Against Epilepsy (ILAE) position paper on Epilepsy Syndromes in Neonates & Infants feel that intellectual disability (ID) is an important mandatory criterion differentiating Dravet syndrome from the many other epilepsy phenotypes within the genetic epilepsy with febrile seizures plus (GEFS+) spectrum, which are also associated with loss-of-function pathogenic variants in the SCN1A gene.² The task force did not define ID based on an IQ score, as there is a variability between individuals with borderline IQ scores in their degree of limitations in intellectual functioning and adaptive behavior. The mandatory features, alerts, and exclusionary criteria tables in the paper refer to the gold standard diagnosis of the established electroclinical syndrome not the syndrome in evolution.²

The ILAE developed the position papers because the boundaries of some epilepsy syndromes were not well delineated or previous studies had used broad or differing diagnostic criteria.³ The syndrome diagnosis criteria, developed by two task forces, peer review and community engagement, provide a consensus to guide clinical practice and research.

The diagnosis of an epilepsy syndrome frequently carries prognostic and treatment implications, and as such it is important that individuals with epilepsies that are self-limited, or that will not be associated with ID, are distinguished from developmental and epileptic encephalopathies. The latest ILAE syndrome definition of Dravet syndrome uses ID to distinguish complex epilepsy phenotypes within the GEFS+ spectrum, which may be therapy resistant but not associated with ID, from Dravet syndrome.⁴

Reilly et al. in their population-based cohorts used diagnostic criteria for Dravet syndrome at onset from 2013 including: (1) normal electroencephalography (EEG) with no pre-existing cerebral lesion in a normal infant; (2) normal development until the first seizure occurring before 1 year of age; (3) refractory clonic or tonic–clonic seizures affecting one or both sides simultaneously or alternatively; and (4) exclusion of any other identified epilepsy syndrome including negative PCDH19 analysis in SCN1A-negative patients.^{5, 6} This definition is relevant for early recognition of individuals who may develop Dravet syndrome at a stage when the syndrome is in evolution. However, many individuals with these clinical features will not have Dravet syndrome. The development of diagnostic prediction scores comprising age at onset and genetic data will provide greater confidence in diagnosis at an earlier stage in the evolution of the syndrome.^{7, 8}

我们很高兴有机会回复这封信：所有 Dravet 综合征患者都有智力障碍吗？来自赖利和同事。¹

国际抗癫痫联盟 (ILAE) 关于新生儿和婴儿癫痫综合征的立场文件的作者认为，智力障碍 (ID) 是区分 Dravet 综合征与伴有热性惊厥的遗传性癫痫中的许多其他癫痫表型的重要强制性标准。 GEFS+）谱，这也与SCN1A基因中功能丧失的致病性变异有关。²工作组并未根据 IQ 分数来定义 ID，因为 IQ 分数处于边缘的个体在智力功能和适应性行为方面的限制程度存在差异。本文中的强制性特征、警报和排除标准表指的是已建立的电临床综合征的金标准诊断，而不是进化中的综合征。²

ILAE 制定了立场文件，因为一些癫痫综合征的界限没有得到很好的界定，或者之前的研究使用了广泛或不同的诊断标准。³由同行评审和社区参与两个工作组制定的综合征诊断标准为指导临床实践和研究提供了共识。

癫痫综合征的诊断通常会对预后和治疗产生影响，因此，将自限性或与智力障碍无关的癫痫患者与发育性脑病和癫痫性脑病区分开来非常重要。 Dravet 综合征的最新 ILAE 综合征定义使用 ID 来区分 GEFS+ 谱内的复杂癫痫表型，该表型可能具有治疗抵抗性，但与 Dravet 综合征无关。⁴

赖利等人。在基于人群的队列中，自 2013 年起，Dravet 综合征发病时使用了诊断标准，包括：(1) 正常婴儿的脑电图 (EEG) 正常，没有预先存在的脑部病变； (2) 发育正常直至1岁前第一次癫痫发作； (3) 同时或交替影响一侧或两侧的难治性阵挛或强直阵挛发作； (4)排除任何其他已确定的癫痫综合征，包括SCN1A阴性患者的PCDH19分析阴性。 ^{5, 6}该定义与在 Dravet 综合征进化阶段早期识别可能患 Dravet 综合征的个体相关。然而，许多具有这些临床特征的人不会患有 Dravet 综合征。包括发病年龄和遗传数据在内的诊断预测评分的开发将为该综合征演变的早期阶段的诊断提供更大的信心。^{7, 8}