Department of Neuropediatrics, ERN EpiCare, French Centre de référence des Épilepsies Rares (CréER), Hôpitaux Universitaires de Strasbourg, Strasbourg, France; Institute for Genetics and Molecular and Cellular Biology (IGBMC), University of Strasbourg, CNRS UMR7104, INSERM U1258, Illkirch, France.
Laboratories of Genetic Diagnosis, Institut de Génétique Médicale d'Alsace (IGMA), Strasbourg University Hospitals Strasbourg France, Strasbourg, France.
Pediatr Neurol. 2024 Oct;159:16-25. doi: 10.1016/j.pediatrneurol.2024.07.007. Epub 2024 Jul 15.
Genetic epilepsy diagnosis is increasing due to technological advancements. Although the use of molecular diagnosis is increasing, chromosomal microarray analysis (CMA) remains an important diagnostic tool for many patients. We aim to explore the role and indications of CMA in epilepsy, given the current genomic advances.
We obtained data from 378 epileptic described patients, who underwent CMA between 2015 and 2021. Different types of syndromic or nonsyndromic epilepsy were represented.
After excluding patients who were undertreated or had missing data, we included 250 patients with treated epilepsy and relevant clinical information. These patients mostly had focal epilepsy or developmental and epileptic encephalopathy, with a median start age of 2 years. Ninety percent of the patients had intellectual disability, more than two thirds had normal head size, and 60% had an abnormal magnetic resonance imaging. We also included 10 patients with epilepsy without comorbidities. In our cohort, we identified 35 pathogenic copy number variations (CNVs) explaining epilepsy with nine recurrent CNVs enriched in patients with epilepsy, 12 CNVs related to neurodevelopmental disorder phenotype with possible epilepsy, five CNVs including a gene already known in epilepsy, and nine CNVs based on size combined with de novo occurrence. The diagnosis rate in our study reached 14% (35 of 250) with first-line CMA, as previously reported. Although targeted gene panel sequencing could potentially diagnose some of the reported epilepsy CNVs (34% [12 of 35]).
CMA remains a viable option as the first-line genetic test in cases where other genetic tests are not available and as a second-line diagnostic technique if gene panel or exome sequencing yields negative results.
由于技术进步，遗传性癫痫诊断正在增加。尽管分子诊断的应用正在增加，但染色体微阵列分析（CMA）仍然是许多患者的重要诊断工具。鉴于当前的基因组学进展，我们旨在探讨 CMA 在癫痫中的作用和适应证。
我们从 2015 年至 2021 年间接受 CMA 的 378 名癫痫患者中获得了数据。不同类型的综合征或非综合征性癫痫均有代表。
排除治疗不足或数据缺失的患者后，我们纳入了 250 名有治疗的癫痫患者和相关临床信息。这些患者大多患有局灶性癫痫或发育性和癫痫性脑病，中位起始年龄为 2 岁。90%的患者有智力障碍，超过三分之二的患者头围正常，60%的患者磁共振成像异常。我们还纳入了 10 名无合并症的癫痫患者。在我们的队列中，我们发现了 35 个致病性拷贝数变异（CNV）可解释癫痫，其中 9 个在癫痫患者中富集的反复出现的 CNV，12 个与神经发育障碍表型相关的可能癫痫的 CNV，5 个包含已知在癫痫中的基因的 CNV，以及 9 个基于大小并伴有新生发生的 CNV。与之前报道的一样，我们的研究中一线 CMA 的诊断率达到 14%（35/250）。尽管靶向基因panel 测序可能潜在地诊断出一些报道的癫痫 CNV（34%[12/35]）。
如果其他基因测试不可用，CMA 仍然是可行的一线遗传测试选择，并且如果基因panel 或外显子测序结果为阴性，CMA 也是二线诊断技术。
