PDF(Pubmed)
Abstract：
Knowledge of underlying genetic causes of developmental and epileptic encephalopathies (DEE) in adults is still limited when compared to the routine diagnostic approach in similarly affected children. A well-documented longitudinal study of adults with DEE is of utmost importance to understand the natural history of the respective entity. This information is of great value especially for genetic counselling of newly diagnosed children with identical genetic diagnoses and may impact treatment and management of affected individuals. In our meta-analysis we provide an overview of the most recurrent genetic findings across an adult DEE cohort (n=1,020). The gene mostly associated with a pathogenic or likely pathogenic variant in adult DEE is SCN1A, followed by MECP2 and CHD2. Studies employing exome sequencing and calling of both single nucleotide variants and copy number variants are associated with diagnostic yields of almost 50 %. Finally, we highlight three remarkable cases, each representing the oldest individual ever published with their genetic diagnosis, i. e., Angelman syndrome, Miller-Dieker syndrome, and CAMK2A-related disorder, and describe lessons learned from each of these adults.
摘要：
与受类似影响的儿童的常规诊断方法相比，对成人发育性和癫痫性脑病（DEE）的潜在遗传原因的了解仍然有限。对DEE成年人进行有据可查的纵向研究对于了解各自实体的自然史至关重要。这些信息特别是对于具有相同基因诊断的新诊断儿童的遗传咨询具有重要价值，并且可能影响受影响个体的治疗和管理。在我们的荟萃分析中，我们概述了成人DEE队列中最反复出现的遗传发现（n=1,020）。与成人DEE中的致病性或可能的致病性变异体主要相关的基因是SCN1A，其次是MECP2和CHD2。采用外显子组测序和单核苷酸变体和拷贝数变体的调用的研究与几乎50%的诊断产率相关。最后,我们强调了三个值得注意的案例，每个都代表着有史以来发表过基因诊断的最古老的个体，i.e.,Angelman综合征,Miller-Dieker综合征,和CAMK2A相关疾病，并描述从这些成年人身上学到的教训。
