Triono A, Herini E S, Mooiindie K H, Iskandar K
Universitas Gadjah Mada/Dr. Sardjito Hospital, Faculty of Medicine, Public Health and Nursing, Neurology Division, Department of Child Health, Yogyakarta Indonesia.
Universitas Gadjah Mada/UGM Academic Hospital, Faculty of Medicine, Public Health and Nursing, Department of Child Health, Neurology Division, Yogyakarta Indonesia.
Med J Malaysia. 2025 Jul;80(4):521-530.
Developmental and epileptic encephalopathy (DEE) is epilepsy related to developmental impairment that may be caused by both the underlying etiology (developmental encephalopathy) and superimposed epileptic activity (epileptic encephalopathy). The origin of DEE and the causes of its variations remain unknown. Owing the lack of clarity regarding the role of genetic variables in DEE, we conducted a scoping review to qualitatively identify the genes most important in the development of DEE to provide an up-to-date review.
We searched all published studies related to the genetic factors of DEE. The identified publications were screened and selected by the authors on basis of on inclusion and exclusion criteria and assessed for methodological quality. Eighteen articles were included. The extracted data included age of onset, sex, gene mutations and inheritance (e.g. nucleotide change, protein change, and family testing), clinical manifestation, electroencephalogram, imaging, medication, and outcomes.
A total of 18 studies were included in this scoping review. The most frequently reported gene variants were STXBP1 in Ohtahara Syndrome, SLC1A2 in Early Myoclonic Encephalopathy (EME), CDKL5 in West Syndrome, SCN1A in Dravet Syndrome, and KCNT1 in Epilepsy of Infancy with Migrating Focal Seizures (EIMFS). Each gene was associated with distinct electroclinical features, including differences in age of onset, seizure type, EEG patterns, and developmental outcomes. While genotype and phenotype associations were heterogeneous, certain variants showed consistent patterns indicative of more severe disease courses.
This review identified key gene variants commonly associated with early-onset DEE in infants, particularly STXBP1, SLC1A2, CDKL5, SCN1A, and KCNT1, each linked to unique clinical presentations and outcomes. These findings support the clinical utility of next-generation sequencing (NGS) for early diagnosis and tailored treatment planning in DEE. Understanding genotype-phenotype correlations may enhance prognostication and highlight potential avenues for targeted therapy in future research.
发育性癫痫性脑病（DEE）是一种与发育障碍相关的癫痫，其可能由潜在病因（发育性脑病）和叠加的癫痫活动（癫痫性脑病）共同引起。DEE的起源及其变异的原因尚不清楚。由于基因变量在DEE中的作用尚不明确，我们进行了一项范围综述，以定性确定在DEE发生发展中最重要的基因，从而提供最新的综述。
我们检索了所有已发表的与DEE遗传因素相关的研究。作者根据纳入和排除标准对识别出的出版物进行筛选和选择，并评估其方法学质量。共纳入18篇文章。提取的数据包括发病年龄、性别、基因突变和遗传方式（如核苷酸变化、蛋白质变化和家系检测）、临床表现、脑电图、影像学、用药情况及预后。
本范围综述共纳入18项研究。最常报道的基因变异有大田原综合征中的STXBP1、早期肌阵挛性脑病（EME）中的SLC1A2、韦斯特综合征中的CDKL5、德雷维特综合征中的SCN1A以及婴儿游走性局灶性癫痫发作（EIMFS）中的KCNT1。每个基因都与独特的电临床特征相关，包括发病年龄、发作类型、脑电图模式和发育结局的差异。虽然基因型与表型的关联具有异质性，但某些变异显示出一致的模式，提示病情进展更为严重。
本综述确定了与婴儿早发性DEE常见相关的关键基因变异，特别是STXBP1、SLC1A2、CDKL5、SCN1A和KCNT1，每个基因都与独特的临床表现和结局相关。这些发现支持了下一代测序（NGS）在DEE早期诊断和个性化治疗规划中的临床应用。了解基因型与表型的相关性可能会改善预后，并为未来研究中的靶向治疗指明潜在途径。
