A retrospective study of the yield of next-generation sequencing in the diagnosis of developmental and epileptic encephalopathies and epileptic encephalopathies in 0–12 years aged children at a single tertiary care hospital in South India

IF 1.9 4区医学 Q3 CLINICAL NEUROLOGY

Epileptic Disorders Pub Date : 2024-06-24 DOI:10.1002/epd2.20254

Manasa C. Murthy, Bidisha Banerjee, Mitesh Shetty, Manikandan Mariappan, Akansha Sekhsaria

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Abstract

Objective

Studies on the genetic yield of developmental and epileptic encephalopathy and Epileptic encephalopathies using next-generation sequencing techniques are sparse from the Indian subcontinent. Hence, the study was conducted to assess the yield of genetic testing and the proportion of children where a positive genetic yield influenced treatment decisions.

Methods

In this retrospective observational study, electronic medical records of children (0–12 years) with suspected genetic epilepsy who underwent genetic testing using whole exome sequencing, focused exome sequencing and epilepsy gene panels were retrieved. Genetic yield was ascertained based on the detection of pathogenic and likely pathogenic variants.

Results

A total of 100 patients with epilepsy underwent genetic testing. A yield of 53.8% (42/78) was obtained. Pathogenic variants were identified in 18 (42.8%) cases and likely pathogenic variants in 24 (57.1%) cases. Yield was 66.6% each through whole exome sequencing, focused exome sequencing and 40% through Epilepsy gene panels (p = .07). Yield was not statistically significant across different age groups (p = .2). It was however found to significantly vary across different epilepsy syndromes with maximum yield in Epilepsy in infancy with migrating focal seizures in 2 (100%), followed by developmental and epileptic encephalopathy unspecified in 14 (77.7%), Dravet syndrome in 14 (60.8%), early infantile developmental and epileptic encephalopathy in 3 (60%), infantile epileptic spasm syndrome in 5 (35.7%), and other epileptic encephalopathies in 4 (30.7%) cases (p = .04). After genetic diagnosis and drug optimization, drug-refractory proportion reduced from 73.8% to 45.3%. About half of the cases achieved seizure control.

Significance

A reasonably high yield of 53.8% was obtained irrespective of the choice of panel or exome or age group using next-generation sequencing-based techniques. Yield was however higher in certain epilepsy syndromes and low in Infantile epileptic spasms syndrome. A specific genetic diagnosis facilitated tailored treatment leading to seizure freedom in 28.6% and marked seizure reduction in 54.7% cases.

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一项回顾性研究，探讨新一代测序技术在南印度一家三甲医院诊断0-12岁儿童发育性癫痫性脑病和癫痫性脑病中的应用。

目的：印度次大陆利用新一代测序技术对发育性脑病、癫痫性脑病和癫痫性脑病遗传率的研究很少。因此，本研究旨在评估基因检测的结果，以及基因检测结果呈阳性对治疗决策产生影响的患儿比例：在这项回顾性观察研究中，检索了疑似遗传性癫痫儿童（0-12 岁）的电子病历，这些儿童接受了全外显子组测序、聚焦外显子组测序和癫痫基因面板的基因检测。根据致病变异和可能致病变异的检测结果确定基因产量：共有 100 名癫痫患者接受了基因检测。结果：共有 100 名癫痫患者接受了基因检测，检测率为 53.8%（42/78）。在 18 个病例（42.8%）中发现了致病变体，在 24 个病例（57.1%）中发现了可能致病的变体。通过全外显子组测序、聚焦外显子组测序和癫痫基因组测序获得的阳性率分别为66.6%和40%（p = .07）。在不同年龄组中，收益率没有统计学意义（p = .2）。然而，研究发现，不同癫痫综合征的基因组测序结果差异很大，其中婴儿癫痫伴移灶性癫痫发作的基因组测序结果最高，有 2 例（100%），其次是发育性和癫痫性脑病未指定的基因组测序结果，有 14 例（77.7%），14 例（60.8%）为德拉韦综合征（Dravet syndrome），3 例（60%）为婴儿早期发育和癫痫性脑病，5 例（35.7%）为婴儿癫痫痉挛综合征，4 例（30.7%）为其他癫痫性脑病（P = .04）。经过基因诊断和药物优化后，药物难治性比例从 73.8% 降至 45.3%。约半数病例的癫痫发作得到了控制：意义：使用基于新一代测序的技术，无论选择的是面板或外显子组还是年龄组，都能获得 53.8% 的相当高的检出率。不过，某些癫痫综合征的诊断率较高，而婴儿癫痫痉挛综合征的诊断率较低。具体的基因诊断有助于进行有针对性的治疗，28.6%的病例摆脱了癫痫发作，54.7%的病例明显减少了癫痫发作。

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

Epileptic Disorders 医学-临床神经学

CiteScore

4.10

自引率

8.70%

发文量

138

审稿时长

6-12 weeks

期刊介绍： Epileptic Disorders is the leading forum where all experts and medical studentswho wish to improve their understanding of epilepsy and related disorders can share practical experiences surrounding diagnosis and care, natural history, and management of seizures. Epileptic Disorders is the official E-journal of the International League Against Epilepsy for educational communication. As the journal celebrates its 20th anniversary, it will now be available only as an online version. Its mission is to create educational links between epileptologists and other health professionals in clinical practice and scientists or physicians in research-based institutions. This change is accompanied by an increase in the number of issues per year, from 4 to 6, to ensure regular diffusion of recently published material (high quality Review and Seminar in Epileptology papers; Original Research articles or Case reports of educational value; MultiMedia Teaching Material), to serve the global medical community that cares for those affected by epilepsy.