Stenshorne Ida, Syvertsen Marte, Ramm-Pettersen Anette, Henning Susanne, Weatherup Elisabeth, Bjørnstad Alf, Brüggemann Natalia, Spetalen Torstein, Selmer Kaja K, Koht Jeanette
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Department of Children and Adolescents, Drammen Hospital, Vestre Viken Health Trust, Drammen, Norway.
Front Pediatr. 2022 Aug 1;10:965282. doi: 10.3389/fped.2022.965282. eCollection 2022.
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.
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.
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 ( and ). 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.
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.
发育性和癫痫性脑病（DEE）是一组癫痫症，其中癫痫活动、发作及潜在的神经生物学因素会导致认知和行为障碍。为制定治疗和随访指南，明确DEE的病因很重要。本研究的目的是描述挪威一家地区医院中病因不明的DEE患者队列的临床表现，并确定其遗传病因。
在韦斯特福尔-泰勒马克郡健康信托基金德拉门医院对病历进行系统检索，以确定1999年至2018年期间的癫痫患者。查阅病历以确定病因不明的DEE患者。2018年，还从治疗医生处连续招募患者。所有患者均接受了全面的临床评估和最新的基因诊断分析。
2225例癫痫患者中有55例患有病因不明的DEE。在纳入研究的33例患者中，有15例（45%）发现了致病基因变异。3例患有潜在可治疗的代谢紊乱（和）。与未确诊的患者相比，基因诊断组的发育合并症更高。发现了已知基因中的5个新变异，并对患者表型进行了描述。
本研究结果表明，对病因不明的DEE患者进行最新的基因调查和/或分析非常重要。45%的患者确定了遗传病因，其中3例患者患有潜在可治疗的疾病，现有靶向治疗可能改善患者预后。
