Dataset Information

Next-generation sequencing improves treatment efficacy and reduces hospitalization in children with drug-resistant epilepsy.

ABSTRACT:

Background

The purposes of this study were three-fold: (i) to determine the contribution of known genes to the causation of a broad-spectrum of pediatric drug-resistant epilepsy (DRE), (ii) to compare the diagnostic yield and cost among different next-generation sequencing (NGS) approaches, and especially (iii) to assess how NGS approaches can benefit patients by improving diagnosis and treatment efficiency.

Methods

This study enrolled 273 pediatric DRE patients with no obvious acquired etiology. Seventy-four patients underwent whole-exome sequencing (WES), 141 patients had epilepsy-related gene panel testing, and another 58 patients had clinical WES gene panel testing. We obtained these patients' seizure and hospitalization frequency by periodic follow-up phone calls and outpatient visits.

Results

Genetic diagnosis was achieved in 86 patients (31.5%) and involved 93 likely disease-causing mutations in 33 genes. In this study, the detection rates of the epilepsy-related gene panel, the clinical WES gene panel, and WES were 32.6% (46/141), 44.8% (26/58), and 17.3% (13/74), respectively. Moreover, 34 patients accepted corrective therapy according to their mutant genes, after which 52.9% (18/34) became seizure-free and 38.2% (13/34) achieved seizure reduction. In the end, patients with either positive or negative genetic results had significantly fewer hospitalization incidents (times/half year) than before (positive genetic results group 0.58 ± 1.14 vs 0.10 ± 0.26; negative genetic results group 0.72 ± 1.65 vs 0.12 ± 0.33).

Conclusions

These results offer further proof that NGS approaches represent powerful tools for establishing a definitive diagnosis. Moreover, this study indicated how NGS can improve treatment efficacy and reduce hospitalization in children with DRE.

SUBMITTER: Peng J

PROVIDER: S-EPMC6436594 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Publications

Next-generation sequencing improves treatment efficacy and reduces hospitalization in children with drug-resistant epilepsy.

Peng Jing J Pang Nan N Wang Ying Y Wang Xiao-Le XL Chen Jian J Xiong Juan J Peng Pan P Zhu Can-Hui CH Kessi Miriam Barakael MB He Fang F Yin Fei F

CNS neuroscience & therapeutics 20180622 1

<h4>Background</h4>The purposes of this study were three-fold: (i) to determine the contribution of known genes to the causation of a broad-spectrum of pediatric drug-resistant epilepsy (DRE), (ii) to compare the diagnostic yield and cost among different next-generation sequencing (NGS) approaches, and especially (iii) to assess how NGS approaches can benefit patients by improving diagnosis and treatment efficiency.<h4>Methods</h4>This study enrolled 273 pediatric DRE patients with no obvious ac ...[more]

PMID: 29933521

Similar Datasets

Project description:Objective:Early onset drug-resistant epilepsy is a neurologic disorder in which 2 antiepileptic drugs fail to maintain the seizure-free status of the patient. Heterogeneous clinical presentations make the diagnosis challenging. We aim to identify the underlying genetic causes of a pediatric cohort with drug-resistant epilepsy and evaluate whether the findings can provide information on patient management. Methods:We include patients with drug-resistant epilepsy onset before 18 years of age. Singleton clinical chromosomal microarray (CMA) followed by whole exome sequencing (WES) was performed using genomic DNA. In the first-tier analysis of the exome data, we aimed to identify disease-causing mutations in 546 genes known to cause, or to be associated with, epilepsy. For negative cases, we proceeded to exome-wide analysis. Rare coding variants were interrogated for pathogenicity based on the American College of Medical Genetics and Genomics (ACMG) guidelines. Results:We recruited 50 patients. We identified 6 pathogenic or likely pathogenic mutations, giving a diagnostic yield of 12%. Mutations were found in 6 different genes: SCN8A, SCN1A, MECP2, CDKL5, DEPDC5, and CHD2. The CDKL5 variant was found to be mosaic. One variant of unknown significance (VUS) in KCNT1 was found in a patient with compatible clinical features. Of note, a reported pathogenic SCN5A mutation known to contribute to Brugada syndrome, was also found in the patient with an SCN1A mutation. Significance:Our study suggests that singleton WES is an effective diagnostic tool for drug-resistant epilepsy. Genetic diagnosis can help to consolidate the clinical diagnosis, to facilitate phenotypic expansion, and to influence treatment and management options for seizure control in our patients. In our study, a significant portion of the genetic findings are known to be associated with an increased risk of sudden unexpected death in epilepsy (SUDEP). These findings could assist with more appropriate management in patients with epilepsy.

Dataset Information

Next-generation sequencing improves treatment efficacy and reduces hospitalization in children with drug-resistant epilepsy.

Background

Methods

Results

Conclusions

Publications

Next-generation sequencing improves treatment efficacy and reduces hospitalization in children with drug-resistant epilepsy.

Similar Datasets

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