Objective: To summarize the clinical phenotype of patients with developmental and epileptic encephalopathy 85 caused by SMC1A gene truncating variation. Methods: The clinical data of 4 patients with epileptic encephalopathy caused by SMC1A gene truncating variation from August 2016 to June 2020 were analyzed retrospectively. Related literatures up to October 2021 with the key words "SMC1A" "Developmental and epileptic encephalopathy 85" "SMC1A, epilepsy" and "SMC1A, truncating" in PubMed, CNKI, and Wanfang databases were searched. Relevant literature was summarized and reviewed. Results: These 4 patients were all female. The onset age of seizure were all in the infantile period. They were admitted to the hospital at 3, 2, 11 and 18 months respectively. Focal seizures occurred in all 4 patients, while 1 of them experienced infantile spasm. The characteristic of cluster was observed in all of them with an interval of 14 days to 5.0 months. The seizures were all refractory to different kinds of anti-seizure medications. All 4 patients had severe developmental retardation with microcephaly (head circumference<-2 s). The interictal electroencephalogram (EEG) was characterized by diffuse slow wave. The 4 SMC1A gene variants were p.Gly655fs, p.Glu811fs, p.Arg412fs and p.Ile143fs, all of which were de novo frameshift variation after parental validation. There were another 17 cases with SMC1A gene truncating variation reported in 6 English articles and 1 Chinese article. Among these 21 patients, who were all female, the onset of seizures occurred between 0.5 and 18.0 months of age. Seventeen cases (81%) had the characteristics of cluster attacks, and the intervals of attack cycles were different. Seizure types included generalized tonic-clonic seizure (12 cases (57%)), focal seizure (11 cases(52%)), myoclonic(4 cases(19%)), spasm (4 cases(19%)), atypical absence (3 cases(14%)), tonic seizure (2 cases (10%)), and atonia (1 case(5%)). In addition, 4 cases (19%) had status epilepsy. All patients had moderate to severe mental retardation. Microcephaly was found in all patients. Among 18 cases,EEG in 8 cases had diffuse slow wave background. Brain magnetic resonance imaging (MRI) was normal in 13 cases (62%). Other MRI changes included cerebellar atrophy (3 cases), thin corpus callosum (3 cases), and lateral ventricular enlargement (2 cases). Twenty patients did not respond well to antiepileptic drugs. Conclusions: The clinical phenotypes of patients with epilepsy encephalopathy 85 caused by SMC1A gene truncating variation are characterized by female, early-onset, clustering of seizures, development delay and microcephaly. Diffuse slow waves are shown in interictal EEG in partial. Response to treatment and prognosis are poor.
目的： 总结SMC1A基因截短变异导致发育性癫痫性脑病85型患儿的临床表型特点。 方法： 回顾性总结2016年8月至2020年6月深圳市儿童医院就诊的4例携带SMC1A基因截短变异所致发育性癫痫性脑病85型患儿的临床资料，并分别以“SMC1A”“癫痫”“发育性癫痫性脑病”“developmental and epileptic encephalopathy 85”“SMC1A，epilepsy”或“SMC1A，truncating”为关键词检索中国知网、万方数据库和PubMed数据库自建库至2021年10月相关文献，筛选存在SMC1A截短变异病例的文献。结合本组病例进行临床表型特点包括起病年龄、性别、癫痫发作类型、发作特点、发育情况、体格检查、辅助检查以及对治疗的反应等的总结分析。 结果： 4例SMC1A基因截短变异患儿均诊断为发育性癫痫性脑病85型，均为女性，均为婴幼儿期起病，就诊年龄分别为3、2、11、18月龄，均有局灶性发作，其中1例合并痉挛发作。癫痫发作均具有丛集性发作特点，1例有癫痫持续状态，发作周期为14 d至5.0个月不等。口服多种抗癫痫发作药物效果均不佳。4例均有重度发育迟缓，均合并小头（头围均<-2 s）。脑电图突出特点为发作间期均见广泛性或弥漫性慢波阵发。4例患儿SMC1A基因变异分别为p.Gly655fs、p.Glu811fs、p.Arg412fs和p.Ile143fs，均为新发移码变异。文献检索相关病例报道共7篇，其中英文6篇、中文1篇，结合本组4例共21例SMC1A基因截短变异导致发育性癫痫性脑病85型患儿，均为女性，起病年龄0.5~18.0月龄，其中17例（81%）具有丛集性发作特点，发作周期间隔时间不等。可有多种发作形式，包括全面强直-阵挛发作［12例（57%）］、局灶性发作［11例（52%）］，肌阵挛［4例（19%）］，痉挛［4例（19%）］，不典型失神［3例（14%）］，强直［2例（10%）］，失张力［1例（5%）］。癫痫持续状态4例（19%）。所有患儿均有中至重度的智力障碍及语言缺失，均合并小头畸形。18例有脑电图资料，其中8例结果提示广泛性或弥漫性慢波背景。颅脑磁共振成像正常13例（62%）。其他改变包括小脑萎缩、胼胝体各3例，侧脑室扩大2例。20例患儿对抗癫痫发作药物治疗反应均不佳。 结论： SMC1A基因截短变异导致癫痫均为女性发病，具有起病年龄早、丛集性发作特点，全面强直阵挛发作及局灶发作常见，伴有严重发育迟缓，语言发育迟缓显著，均合并小头畸形，脑电图可见广泛或弥漫性慢波特征，对治疗反应差，预后不佳。.