Department of Neurology, Keck School of Medicine of the University of Southern California, Los Angeles, California.
Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Center for Personalized Medicine, Los Angeles, California.
Pediatr Neurol. 2024 Jan;150:50-56. doi: 10.1016/j.pediatrneurol.2023.10.014. Epub 2023 Oct 27.
Around 40% of individuals with epilepsy have an underlying identifiable genetic etiology. Common methods for epilepsy genetic testing are chromosomal microarray (CMA) and epilepsy-genes sequencing (EGS). Historically, CMA was the first-line test for patients with epilepsy, but recent studies have shown that EGS has a superior diagnostic yield. To further optimize testing algorithms for epilepsy, we compared these tests' diagnostic yields and explored how they are influenced by age of onset and phenotype complexity.
Genetic test results from a cohort of patients with epilepsy were used to determine the diagnostic yield of CMA (n = 366) versus EGS (n = 370) for genetic epilepsy etiologies. Further analysis examined the probability of diagnostic results based on age of seizure onset and patients' phenotype complexity.
For patients who underwent CMA, causative variants were found in 28 of 366 cases (7.7%), and 60 of 366 patients (16.4%) had at least one variant of uncertain significance (VUS). For EGS, 65 of 370 (17.6%) cases had causative variants, whereas 155 of 370 (41.9%) had at least one VUS. EGS had a significantly higher diagnostic yield than CMA (odds ratio [OR] = 2.63, P < 0.001). This difference in diagnostic yield was further pronounced among patients with infantile seizure onset (OR = 4.69, P < 0.001) and patients with additional neurological findings (OR = 2.99, P < 0.001).
To minimize the time and resources required to reach a diagnosis, clinicians and insurers alike should consider using EGS as an initial diagnostic tool.
约 40%的癫痫患者存在潜在的可识别遗传病因。癫痫遗传学检测的常用方法是染色体微阵列（CMA）和癫痫基因测序（EGS）。历史上，CMA 是癫痫患者的一线检测方法，但最近的研究表明 EGS 具有更高的诊断收益。为了进一步优化癫痫检测算法，我们比较了这两种检测方法的诊断收益，并探讨了它们如何受到发病年龄和表型复杂性的影响。
使用癫痫患者队列的基因检测结果，确定 CMA（n=366）与 EGS（n=370）对遗传癫痫病因的诊断收益。进一步的分析检查了基于发病年龄和患者表型复杂性的诊断结果的概率。
在接受 CMA 的患者中，在 366 例病例中有 28 例（7.7%）发现了致病变异，在 366 例患者中有 60 例（16.4%）存在至少一个意义不明的变异（VUS）。在 EGS 中，370 例病例中有 65 例（17.6%）存在致病变异，而在 370 例中有 155 例（41.9%）存在至少一个 VUS。EGS 的诊断收益明显高于 CMA（比值比[OR] = 2.63，P < 0.001）。在婴儿起病的患者（OR = 4.69，P < 0.001）和有额外神经学发现的患者（OR = 2.99，P < 0.001）中，这种诊断收益的差异更为显著。
为了最大限度地减少达到诊断所需的时间和资源，临床医生和保险公司都应该考虑将 EGS 作为初始诊断工具。
