Diagnostic Yield of Epilepsy Panels in Children With Medication-Refractory Epilepsy

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• 作者：Eric Segal ; MD^a ; ^{esegal@epilepsygroup.com" class="auth_mail" title="E-mail the corresponding author} ; Helio Pedro ; MD^b ; Karen Valdez-Gonzalez ; MS^b ; Sarah Parisotto ; MS^b ; Felicia Gliksman ; MD^c ; Stephen Thompson ; MD^c ; Jomard Sabri ; BA^a ; Evan Fertig ; MD^a
• 关键词：gene panel ; next-generation sequencing ; children ; epilepsy
• 刊名：Pediatric Neurology
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：64
• 期：Complete
• 页码：66-71
• 全文大小：191 K

文摘

When no chromosomal variations are identified, patients with suspected genetic etiologies can be tested using next-generation sequencing utilizing epilepsy panels. The primary objective of this study was to analyze the diagnostic yield of next-generation sequencing epilepsy panels in medication-resistant epilepsy subjects with non–clinically significant comparative genomic hybridization microarray results.

c_2">Methods

We completed a single-center retrospective review of the diagnostic yield of next-generation sequencing epilepsy panels in medication-resistant epilepsy subjects aged 18 years or less who had non–clinically significant comparative genomic hybridization microarray results from January 2011 to December 2014. The primary end point was the yield of clinically significant next-generation sequencing results.

c_3">Results

Forty-nine subjects (21 male) with medication-refractory epilepsy and clinically in significant comparative genomic hybridization microarray results were identified. Next-generation sequencing abnormalities were seen in 28 subjects (57%): seven of these 28 subjects (25%) had clinically significant findings. Mutations were found in the SCN1A gene in three subjects, in the PCDH19 gene in two subjects, and in DLG3, MECP2, TSC2, and SLC9A6 genes in one subject each. Only the MECP2 mutation was found to be pathogenic in this last subject. The additional yield of next-generation sequencing with uninformative chromosomal microarray was 14%. Positive findings were primarily seen in those with Dravet syndrome, all with SCN1A mutations (42% of clinically significant results). Given the small sample size, a larger prospective study would help to determine the clinical yield of next-generation sequencing.

c_4">Conclusion

Next-generation sequencing seizure panels could be a useful tool in the diagnosis of nonacquired pediatric medication-refractory epilepsy with uninformative comparative genomic hybridization microarray.