Division of Neurology, Department of Paediatrics, McMaster University, Hamilton, Ontario, Canada.
Epilepsy Program, Division of Neurology, Department of Paediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Epilepsia Open. 2023 Jun;8(2):623-632. doi: 10.1002/epi4.12747. Epub 2023 Apr 24.
ST3GAL3-related developmental and epileptic encephalopathy (DEE-15) is an autosomal recessive condition characterized by intellectual disability, language and motor impairments, behavioral difficulties, stereotypies, and epilepsy. Only a few cases have been reported, and the epilepsy phenotype is not fully elucidated.
A retrospective chart review of two siblings with ST3GAL3-related DEE was completed. In addition, we reviewed all published cases of ST3GAL3-related congenital disorder of glycosylation.
Two brothers presented with global developmental delay, motor and language impairment, hypotonia, and childhood-onset seizures. Seizures started between 2.5 and 5 years and had tonic components. Both siblings had prolonged periods of seizure freedom on carbamazepine. Tremor was present in the younger sibling. Whole exome sequencing revealed two novel pathogenic variants in ST3GAL3, (a) c.302del, p.Phe102Serfs34 and (b) c.781C>T, p.Arg261, which were inherited in trans. Magnetic resonance imaging showed T2 hyperintensities and restricted diffusion in the brainstem and middle cerebellar peduncle in the older sibling, also described in two reported cases. A review of the literature revealed 24 cases of ST3GAL3-related CDG. Twelve cases had information about seizures, and epilepsy was diagnosed in 8 (67%). The median age of seizure onset was 5.5 months. Epileptic spasms were most common (67%). Four children were diagnosed with Infantile Epileptic Spasms syndrome and Lennox Gastaut syndrome (57%). Most children (n = 6, 75%) had seizures despite anti-seizure medication treatment.
Seizures related to ST3GAL3-related DEE often occur in infancy and may present as epileptic spasms. However, seizure onset may also occur outside of infancy with mixed seizure types and show good response to treatment with prolonged seizure freedom. Tremor may also be uniquely observed in this condition.
ST3GAL3 相关发育性和癫痫性脑病（DEE-15）是一种常染色体隐性疾病，其特征为智力障碍、语言和运动障碍、行为困难、刻板行为和癫痫。仅有少数病例报道，且癫痫表型尚未完全阐明。
对两名 ST3GAL3 相关 DEE 患者进行回顾性病历分析。此外，我们还回顾了所有已发表的 ST3GAL3 相关先天性糖基化障碍病例。
两名兄弟均表现为全面发育迟缓、运动和语言障碍、肌张力低下和儿童期起病的癫痫。癫痫发作始于 2.5 至 5 岁之间，具有强直成分。两名患者均在服用卡马西平期间有较长时间的无癫痫发作。弟弟存在震颤。全外显子组测序发现 ST3GAL3 中存在两个新的致病性变异（a）c.302del，p.Phe102Serfs34 和（b）c.781C>T，p.Arg261，为同胞兄妹之间的共传递遗传。磁共振成像显示，年龄较大的患者脑干和小脑中脑脚 T2 高信号和弥散受限，在两名已报道的病例中也有描述。文献回顾发现 24 例 ST3GAL3 相关 CDG。12 例有癫痫发作信息，其中 8 例（67%）诊断为癫痫。癫痫发作的中位年龄为 5.5 个月。癫痫发作最常见的是痉挛性发作（67%）。4 名儿童被诊断为婴儿痉挛症和 Lennox-Gastaut 综合征（57%）。大多数患儿（n=6，75%）尽管接受了抗癫痫药物治疗仍有癫痫发作。
ST3GAL3 相关 DEE 相关的癫痫发作常发生于婴儿期，可能表现为痉挛性发作。然而，癫痫发作也可发生于婴儿期之外，具有混合性癫痫发作类型，且对治疗反应良好，无癫痫发作的时间较长。震颤也可能是该疾病的独特表现。
