Sheidley Beth R, Malinowski Jennifer, Bergner Amanda L, Bier Louise, Gloss David S, Mu Weiyi, Mulhern Maureen M, Partack Emily J, Poduri Annapurna
Epilepsy Genetics Program, Division of Epilepsy and Neurophysiology, Department of Neurology, Boston Children's Hospital, Boston, Massachusetts, USA.
Write Inscite, South Salem, New York, USA.
Epilepsia. 2022 Feb;63(2):375-387. doi: 10.1111/epi.17141. Epub 2021 Dec 10.
Numerous genetic testing options for individuals with epilepsy have emerged over the past decade without clear guidelines regarding optimal testing strategies. We performed a systematic evidence review (SER) and conducted meta-analyses of the diagnostic yield of genetic tests commonly utilized for patients with epilepsy. We also assessed nonyield outcomes (NYOs) such as changes in treatment and/or management, prognostic information, recurrence risk determination, and genetic counseling.
We performed an SER, in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), using PubMed, Embase, CINAHL, and Cochrane Central through December of 2020. We included studies that utilized genome sequencing (GS), exome sequencing (ES), multigene panel (MGP), and/or genome-wide comparative genomic hybridization/chromosomal microarray (CGH/CMA) in cohorts (n ≥ 10) ascertained for epilepsy. Quality assessment was undertaken using ROBINS-I (Risk of Bias in Non-Randomized Studies of Interventions). We estimated diagnostic yields and 95% confidence intervals with random effects meta-analyses and narratively synthesized NYOs.
From 5985 nonduplicated articles published through 2020, 154 met inclusion criteria and were included in meta-analyses of diagnostic yield; 43 of those were included in the NYO synthesis. The overall diagnostic yield across all test modalities was 17%, with the highest yield for GS (48%), followed by ES (24%), MGP (19%), and CGH/CMA (9%). The only phenotypic factors that were significantly associated with increased yield were (1) the presence of developmental and epileptic encephalopathy and/or (2) the presence of neurodevelopmental comorbidities. Studies reporting NYOs addressed clinical and personal utility of testing.
This comprehensive SER, focused specifically on the literature regarding patients with epilepsy, provides a comparative assessment of the yield of clinically available tests, which will help shape clinician decision-making and policy regarding insurance coverage for genetic testing. We highlight the need for prospective assessment of the clinical and personal utility of genetic testing for patients with epilepsy and for standardization in reporting patient characteristics.
在过去十年中，针对癫痫患者出现了众多基因检测选项，但对于最佳检测策略尚无明确指南。我们进行了一项系统证据综述（SER），并对癫痫患者常用基因检测的诊断率进行了荟萃分析。我们还评估了非检测阳性结果（NYO），如治疗和/或管理的变化、预后信息、复发风险判定以及遗传咨询。
我们按照PRISMA（系统评价和荟萃分析优先报告项目）进行了一项SER，通过PubMed、Embase、CINAHL和Cochrane Central检索截至2020年12月的文献。我们纳入了在确诊为癫痫的队列（n≥10）中使用基因组测序（GS）、外显子组测序（ES）、多基因检测板（MGP）和/或全基因组比较基因组杂交/染色体微阵列（CGH/CMA）的研究。使用ROBINS-I（干预非随机研究中的偏倚风险）进行质量评估。我们通过随机效应荟萃分析估计诊断率和95%置信区间，并对NYO进行叙述性综合分析。
在截至2020年发表的5985篇非重复文章中，154篇符合纳入标准并被纳入诊断率的荟萃分析；其中43篇被纳入NYO综合分析。所有检测方式的总体诊断率为17%，GS的诊断率最高（48%），其次是ES（24%）、MGP（19%）和CGH/CMA（9%）。与诊断率增加显著相关的唯一表型因素是：（1）存在发育性和癫痫性脑病，以及/或者（2）存在神经发育合并症。报告NYO的研究探讨了检测的临床和个人效用。
这项全面的SER专门聚焦于癫痫患者的文献，对临床可用检测的诊断率进行了比较评估，这将有助于指导临床医生在基因检测保险覆盖方面的决策和制定政策。我们强调需要对癫痫患者基因检测的临床和个人效用进行前瞻性评估，并在报告患者特征方面实现标准化。
