背景:发育性和癫痫性脑病(DEE)包括一组罕见疾病,具有遗传和遗传原因以及获得性原因,例如脑损伤或代谢异常。磷酸呋喃酸性簇分选蛋白2(PACS2)是一种具有核基因表达的多功能蛋白。Olson等人在2018年报道了第一例复发的c.625G>PACS2基因的致病变异。从那以后,已经发表了一些病例报告和病例系列。
方法:我们使用系统评价和荟萃分析的首选报告项目(PRISMA)指南对PUBMED和SCOPUS数据库进行了系统评价。我们的搜索参数包括具有致病性PACS2基因p.Glu209Lys突变的DEE66已发表病例,我们在该病例中添加了我们自己的有关该病理学的临床经验。
结果:本综述共纳入11篇文献和29例患者,我们为总共30名患者添加了自己的经验。关于这种病理的发生率,性别之间没有显着差异(M/F:16/14)。患者最常见的神经和精神症状是:早发性癫痫发作,全球发展延迟(包括运动和语言延迟),行为障碍,智力有限,眼球震颤,低张力,和广泛的步态。面部畸形和其他器官受累也经常被报道。脑部MRI显示小脑后窝异常,小脑的叶面变形,蚯蚓发育不全,白质减少,侧脑室增大.基因检测在儿童中更为常见。迄今为止,仅有4例成人病例报告。
结论:在表现出与放射学改变相关的特征性临床表现的成年患者中,高度怀疑新的致病基因变异是很重要的。神经科医生必须逐渐认识到DEE66在成年患者中的独特进化表型,和基因检测必须成为一个场景,参加成年患者的神经科医生应该熟悉。需要准确的诊断才能进行适当的治疗,遗传咨询,和改善长期预后。
BACKGROUND: Developmental and epileptic encephalopathies (DEE) encompass a group of rare diseases with hereditary and genetic causes as well as acquired causes such as brain injuries or metabolic abnormalities. The phosphofurin acidic cluster sorting protein 2 (PACS2) is a multifunctional protein with nuclear gene expression. The first cases of the recurrent c.625G>A pathogenic variant of PACS2 gene were reported in 2018 by Olson et al. Since then, several case reports and case series have been published.
METHODS: We performed a systematic review of the PUBMED and SCOPUS databases using Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Our search parameters included DEE66 with a pathogenic PACS2 gene p.Glu209Lys mutation published cases to which we added our own clinical experience regarding this pathology.
RESULTS: A total of 11 articles and 29 patients were included in this review, to which we added our own experience for a total of 30 patients. There was not a significant difference between sexes regarding the incidence of this pathology (M/F: 16/14). The most common neurological and psychiatric symptoms presented by the patients were: early onset epileptic seizures, delayed global development (including motor and speech delays), behavioral disturbances, limited intellectual capacity, nystagmus, hypotonia, and a wide-based gait. Facial dysmorphism and other organs\' involvement were also frequently reported. Brain MRIs evidenced anomalies of the posterior cerebellar fossa, foliar distortion of the cerebellum, vermis hypoplasia, white matter reduction, and lateral ventricles enlargement. Genetic testing is more frequent in children. Only 4 cases have been reported in adults to date.
CONCLUSIONS: It is important to maintain a high suspicion of new pathogenic gene variants in adult patients presenting with a characteristic clinical picture correlated with radiologic changes. The neurologist must gradually recognize the distinct evolving phenotype of DEE66 in adult patients, and genetic testing must become a scenario with which the neurologist attending adult patients should be familiar. Accurate diagnosis is required for adequate treatment, genetic counseling, and an improved long-term prognosis.