PDF(Pubmed)
Abstract：
UNASSIGNED: Developmental and epileptic encephalopathies (DEE) is a group of epilepsies where the epileptic activity, seizures and the underlying neurobiology contributes to cognitive and behavioral impairments. Uncovering the causes of DEE is important in order to develop guidelines for treatment and follow-up. The aim of the present study was to describe the clinical picture and to identify genetic causes in a patient cohort with DEE without known etiology, from a Norwegian regional hospital.
UNASSIGNED: Systematic searches of medical records were performed at Drammen Hospital, Vestre Viken Health Trust, to identify patients with epilepsy in the period 1999-2018. Medical records were reviewed to identify patients with DEE of unknown cause. In 2018, patients were also recruited consecutively from treating physicians. All patients underwent thorough clinical evaluation and updated genetic diagnostic analyses.
UNASSIGNED: Fifty-five of 2,225 patients with epilepsy had DEE of unknown etiology. Disease-causing genetic variants were found in 15/33 (45%) included patients. Three had potentially treatable metabolic disorders (SLC2A1, COQ4 and SLC6A8). Developmental comorbidity was higher in the group with a genetic diagnosis, compared to those who remained undiagnosed. Five novel variants in known genes were found, and the patient phenotypes are described.
UNASSIGNED: The results from this study illustrate the importance of performing updated genetic investigations and/or analyses in patients with DEE of unknown etiology. A genetic cause was identified in 45% of the patients, and three of these patients had potentially treatable conditions where available targeted therapy may improve patient outcome.
UNASSIGNED: Systematic searches of medical records were performed at Drammen Hospital, Vestre Viken Health Trust, to identify patients with epilepsy in the period 1999-2018. Medical records were reviewed to identify patients with DEE of unknown cause. In 2018, patients were also recruited consecutively from treating physicians. All patients underwent thorough clinical evaluation and updated genetic diagnostic analyses.
UNASSIGNED: Fifty-five of 2,225 patients with epilepsy had DEE of unknown etiology. Disease-causing genetic variants were found in 15/33 (45%) included patients. Three had potentially treatable metabolic disorders (SLC2A1, COQ4 and SLC6A8). Developmental comorbidity was higher in the group with a genetic diagnosis, compared to those who remained undiagnosed. Five novel variants in known genes were found, and the patient phenotypes are described.
UNASSIGNED: The results from this study illustrate the importance of performing updated genetic investigations and/or analyses in patients with DEE of unknown etiology. A genetic cause was identified in 45% of the patients, and three of these patients had potentially treatable conditions where available targeted therapy may improve patient outcome.
摘要：
■发育性和癫痫性脑病（DEE）是一组癫痫，其中癫痫活动，癫痫发作和潜在的神经生物学有助于认知和行为障碍。发现DEE的原因对于制定治疗和随访指南很重要。本研究的目的是描述临床表现，并在没有已知病因的DEE患者队列中确定遗传原因。来自挪威地区医院。
■在Drammen医院进行了系统的医疗记录搜索，VestreViken健康信托基金,确定1999-2018年期间的癫痫患者.对病历进行了审查，以确定原因不明的DEE患者。2018年，患者也连续从治疗医生中招募。所有患者都接受了全面的临床评估和更新的基因诊断分析。
■2,225例癫痫患者中有55例病因不明的DEE。在15/33（45％）的患者中发现了致病的遗传变异。三人患有潜在可治疗的代谢紊乱（SLC2A1，COQ4和SLC6A8）。在有基因诊断的人群中，发育共病较高，与那些仍未诊断的人相比。在已知基因中发现了五个新的变异，并描述了患者的表型。
■这项研究的结果说明了在病因不明的DEE患者中进行更新的遗传调查和/或分析的重要性。在45％的患者中发现了遗传原因，其中3例患者有潜在可治疗的疾病,可用的靶向治疗可以改善患者预后.
■在Drammen医院进行了系统的医疗记录搜索，VestreViken健康信托基金,确定1999-2018年期间的癫痫患者.对病历进行了审查，以确定原因不明的DEE患者。2018年，患者也连续从治疗医生中招募。所有患者都接受了全面的临床评估和更新的基因诊断分析。
■2,225例癫痫患者中有55例病因不明的DEE。在15/33（45％）的患者中发现了致病的遗传变异。三人患有潜在可治疗的代谢紊乱（SLC2A1，COQ4和SLC6A8）。在有基因诊断的人群中，发育共病较高，与那些仍未诊断的人相比。在已知基因中发现了五个新的变异，并描述了患者的表型。
■这项研究的结果说明了在病因不明的DEE患者中进行更新的遗传调查和/或分析的重要性。在45％的患者中发现了遗传原因，其中3例患者有潜在可治疗的疾病,可用的靶向治疗可以改善患者预后.
