Diagnostic evaluation of patients with epileptic spasms in the era of next-generation sequencing

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-07-01 DOI:10.1002/epd2.20259

Ali Mir, Mohammed AlQahtani, Fawzia Amer, Raidah AlBaradie, Wajd AlOtaibi, Fouad AlGhamdi, Hamoud Khallaf, Shahid Bashir, Gregory Costain, Liali Aljouda, Yousef Housawi

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Abstract

Objective

Epileptic spasms (ES) can be caused by a variety of etiologies. However, in almost half of cases, the etiology is unidentified. With the advent of next-generation sequencing (NGS), the recognition of genetic etiologies has increased.

Methods

We retrospectively reviewed the medical records of patients with ES who were evaluated in the comprehensive epilepsy program at King Fahad Specialist Hospital Dammam between 2009 and 2022.

Results

Our data show that in 57.7% of patients with ES, the etiology was unidentified after a standard clinical evaluation and neuroimaging. Of these patients, n = 25 (35.2%) received a genetic diagnosis after some form of genetic testing, and 3.1% of patients from specialized metabolic work indicated the need for genetic testing to confirm the diagnosis. Karyotyping led to a diagnosis in 3.6% of patients, and chromosomal microarray led to a diagnosis in 7.1%. An NGS epilepsy gene panel (EP) was done for 45 patients, leading to a diagnosis in 24.4% (n = 11). Exome sequencing was done for 27 patients, including n = 14 with non-diagnostic panel testing; it led to a diagnosis in 37.3% (n = 10). Exome sequencing led to a diagnosis in 61.5% of patients without a previous panel test and in only two patients who had previously had a negative panel testing.

Significance

In this article, we present the diagnostic evaluations of ES for a cohort of 123 patients and discuss the yield and priority of NGS for evaluating ES. Our findings suggest that exome sequencing has a higher diagnostic yield for determining the etiology of ES in patients for whom the etiology is still unclear after an appropriate clinical assessment and a brain MRI.

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新一代测序时代癫痫痉挛患者的诊断评估。

目的：癫痫性痉挛（ES）可由多种病因引起。然而，几乎有一半的病例病因不明。随着下一代测序技术（NGS）的出现，对遗传病因的认识也在不断提高：我们回顾性审查了 2009 年至 2022 年期间在达曼法赫德国王专科医院接受综合癫痫项目评估的 ES 患者的病历：我们的数据显示，57.7%的 ES 患者在经过标准临床评估和神经影像学检查后病因不明。在这些患者中，n = 25（35.2%）人在经过某种形式的基因检测后获得了基因诊断，3.1%的专业代谢工作患者表示需要进行基因检测以确诊。有 3.6% 的患者通过核型检查确诊，7.1% 的患者通过染色体微阵列检查确诊。对 45 名患者进行了 NGS 癫痫基因面板 (EP)，结果 24.4% 的患者（n = 11）确诊。对 27 例患者进行了外显子组测序，其中包括 14 例未进行诊断性基因组检测的患者；37.3% 的患者（10 例）通过外显子组测序确诊。外显子组测序使61.5%既往未进行过全套检测的患者获得了诊断，只有两名既往全套检测结果为阴性的患者获得了诊断：在这篇文章中，我们介绍了对一组 123 名患者进行的 ES 诊断评估，并讨论了 NGS 在评估 ES 方面的收益和优先权。我们的研究结果表明，对于经过适当的临床评估和脑磁共振成像检查后病因仍不明确的患者，外显子组测序在确定 ES 病因方面具有更高的诊断率。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.