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

Peng, Jing; Pang, nan sim; Wang, Ying; Wang, Xiao‐Le; Chen, Jian; Xiong, Juan; Pan, Peng; Zhu, Canhui; Kessi, Miriam; He, Fang; Yin, Fei

doi:10.1111/cns.12869

Cited by 51 publications

(46 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Evidence in support of precision therapy in epilepsy varies in level and nature. In 2019, the majority of truly medically ‘actionable’ genetic diagnoses in epilepsy relate to inherited disorders of metabolism such as Glut1 deficiency, and pyridoxine dependency ( Peng et al , 2019 ). Questions remain unanswered in relation to targeted treatment of other genetic causes of epilepsy.…”

Section: Discussionmentioning

confidence: 99%

Incidence and phenotypes of childhood-onset genetic epilepsies: a prospective population-based national cohort

Symonds

Zuberi

Stewart

et al. 2019

Brain

303

264

View full text Add to dashboard Cite

Epilepsy is common in early childhood. In this age group it is associated with high rates of therapy-resistance, and with cognitive, motor, and behavioural comorbidity. A large number of genes, with wide ranging functions, are implicated in its aetiology, especially in those with therapy-resistant seizures. Identifying the more common single-gene epilepsies will aid in targeting resources, the prioritization of diagnostic testing and development of precision therapy. Previous studies of genetic testing in epilepsy have not been prospective and population-based. Therefore, the population-incidence of common genetic epilepsies remains unknown. The objective of this study was to describe the incidence and phenotypic spectrum of the most common single-gene epilepsies in young children, and to calculate what proportion are amenable to precision therapy. This was a prospective national epidemiological cohort study. All children presenting with epilepsy before 36 months of age were eligible. Children presenting with recurrent prolonged (>10 min) febrile seizures; febrile or afebrile status epilepticus (>30 min); or with clusters of two or more febrile or afebrile seizures within a 24-h period were also eligible. Participants were recruited from all 20 regional paediatric departments and four tertiary children’s hospitals in Scotland over a 3-year period. DNA samples were tested on a custom-designed 104-gene epilepsy panel. Detailed clinical information was systematically gathered at initial presentation and during follow-up. Clinical and genetic data were reviewed by a multidisciplinary team of clinicians and genetic scientists. The pathogenic significance of the genetic variants was assessed in accordance with the guidelines of UK Association of Clinical Genetic Science (ACGS). Of the 343 patients who met inclusion criteria, 333 completed genetic testing, and 80/333 (24%) had a diagnostic genetic finding. The overall estimated annual incidence of single-gene epilepsies in this well-defined population was 1 per 2120 live births (47.2/100 000; 95% confidence interval 36.9–57.5). PRRT2 was the most common single-gene epilepsy with an incidence of 1 per 9970 live births (10.0/100 000; 95% confidence interval 5.26–14.8) followed by SCN1A: 1 per 12 200 (8.26/100 000; 95% confidence interval 3.93–12.6); KCNQ2: 1 per 17 000 (5.89/100 000; 95% confidence interval 2.24–9.56) and SLC2A1: 1 per 24 300 (4.13/100 000; 95% confidence interval 1.07–7.19). Presentation before the age of 6 months, and presentation with afebrile focal seizures were significantly associated with genetic diagnosis. Single-gene disorders accounted for a quarter of the seizure disorders in this cohort. Genetic testing is recommended to identify children who may benefit from precision treatment and should be mainstream practice in early childhood onset epilepsy.

show abstract

Section: Discussionmentioning

confidence: 99%

Incidence and phenotypes of childhood-onset genetic epilepsies: a prospective population-based national cohort

Symonds

Zuberi

Stewart

et al. 2019

Brain

303

264

View full text Add to dashboard Cite

show abstract

“…Tuberous sclerosis Cell growth mTOR inhibitors and vigabatrin AD 0.3-3.1% 40,41,46,49,[51][52][53] Abbreviations: AR, autosomal recessive; AD, autosomal dominant; XLD, X-linked dominant; XLR, X-linked recessive.…”

Section: Tsc2mentioning

confidence: 99%

Genetic Testing in Epilepsy

Ritter

Holland

2020

Semin Neurol

View full text Add to dashboard Cite

Because of next-generation sequencing and the discovery of many new causative genes, genetic testing in epilepsy patients has become widespread. Pathologic variants resulting in epilepsy cause a variety of changes that can be broadly classified into syndromic disorders (i.e., chromosomal abnormalities), metabolic disorders, brain malformations, and abnormal cellular signaling. Here, we review the available genetic testing, reasons to pursue genetic testing, common genetic causes of epilepsy, the data behind what patients are found to have genetic epilepsies based on current testing, and discussing these results with patients. We propose an algorithm for testing patients with epilepsy to maximize yield and limit costs based on their phenotype (including electroencephalography and magnetic resonance imaging findings), age of seizure onset, and presence of other neurologic comorbidities. Being able to discern which type of genetic testing to order, using that information to give targeted and cost-effective patient care, and interpreting results accurately will be a crucial skill for the modern neurologist.

show abstract

“…Genetic Characteristics In Drug-resistant Epilepsy Of Published Studies Table 3 provides a summary of previous studies about genetic characteristics in DRE [12][13][14][15][16][17][18][19][20][21]. Regardless of varied molecular diagnostic tool used between studies, some gene mutations were found to appear repeatedly, such as SCN1A (5.6%, n = 74/1308), followed by SCN8A (1.37%, n = 18/1308), TSC2 (1.22%, n = 16/1308), SCN2A (1.07%, n = 14/1308) and KCNQ2 (0.99%, n = 13/1308) 3).…”

Section: Discussionmentioning

confidence: 99%

Genetic factors and the risk of drug-resistant epilepsy in young children with epilepsy and neurodevelopment disability: A Prospective Study and Updated Meta-Analysis

Lin

Chou

Hong

2020

Preprint

View full text Add to dashboard Cite

Background Drug-resistant epilepsy (DRE) affects 7–20% of children with epilepsy. Although some risk factors for DRE have been identified, the results have not been consistent. Moreover, data regarding the risk factors for epilepsy and its seizure outcome in the first 2 years of life are limited. Methods We analyzed data for children aged 0–2 years with epilepsy and neurodevelopmental disability (NDD) from January, 2013, through December, 2017. These patients were followed up to compared the risk of DRE in patients with genetic defect (genetic group) with that without genetic defect (nongenetic group). Additionally, we conducted a meta-analysis to identify the pooled prevalence of genetic factors in children with DRE Results A total of 96 patients were enrolled. A total of 68 patients were enrolled in the nongenetic group, whereas 28 patients were enrolled in the genetic group. The overall DRE risk in the genetic group was 6.5 times (95% confidence interval [CI], 2.15–19.6; p = 0.03) higher than that in the nongenetic group. Separately, a total of 1308 DRE patients were participated in the meta-analysis. The pooled prevalence of these patients with genetic factors was 22.8% (95% CI 17.4–29.3) Conclusions The genetic defect plays a crucial role in the development of DRE in younger children with epilepsy and NDD. The results can serve as a reference for further studies of epilepsy panel design and may also assist in the development of improved treatments and prevention strategies for DRE.

show abstract

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

Abstract: 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.

Cited by 51 publications

References 40 publications

Incidence and phenotypes of childhood-onset genetic epilepsies: a prospective population-based national cohort

Incidence and phenotypes of childhood-onset genetic epilepsies: a prospective population-based national cohort

Genetic Testing in Epilepsy

Genetic factors and the risk of drug-resistant epilepsy in young children with epilepsy and neurodevelopment disability: A Prospective Study and Updated Meta-Analysis

Contact Info

Product

Resources

About