Department of Pathophysiology, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania.
Department of Neurology, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania.
Biomolecules. 2024 Feb 23;14(3):270. doi: 10.3390/biom14030270.
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 gene were reported in 2018 by Olson et al. Since then, several case reports and case series have been published.
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 gene p.Glu209Lys mutation published cases to which we added our own clinical experience regarding this pathology.
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.
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.
发育性和癫痫性脑病 (DEE) 涵盖一组罕见疾病，其病因既有遗传性和基因性的，也有后天性的，如脑损伤或代谢异常。磷酸化富磷酸性簇分选蛋白 2 (PACS2) 是一种具有核基因表达的多功能蛋白。Olson 等人于 2018 年首次报道了基因 c.625G>A 致病性变异的复发性病例。此后，陆续有病例报告和病例系列发表。
我们按照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 DEE66 与致病性基因 p.Glu209Lys 突变相关的已发表病例，我们还加入了自己在该病理学方面的临床经验。
共有 11 篇文章和 29 名患者纳入本综述，我们还加入了自己的经验，共计 30 名患者。该病理学的发病率在性别之间没有显著差异 (男/女：16/14)。患者最常见的神经和精神症状包括：早期癫痫发作、全面发育迟缓（包括运动和言语迟缓）、行为障碍、智力有限、眼球震颤、肌张力低下和宽基步态。面部畸形和其他器官受累也经常被报道。脑 MRI 显示后小脑窝异常、小脑叶片扭曲、蚓部发育不全、白质减少和侧脑室扩大。基因检测在儿童中更为常见。迄今为止，只有 4 例在成人中报告。
对于表现出与影像学变化相关的特征性临床症状的成年患者，重要的是要对新的致病性基因突变保持高度怀疑。神经科医生必须逐渐认识到 DEE66 在成年患者中的独特演变表型，神经科医生应熟悉基因检测这一方案。准确的诊断是进行充分治疗、遗传咨询和改善长期预后的必要条件。
