The role of targeted gene panel in pediatric drug-resistant epilepsy

Wu, Chang-Chun; Tsai, Meng-Han; Chu, Yen-Ju; Weng, Wen‐Chin; Fan, Pi‐Chuan; Lee, Wang-Tso

doi:10.1016/j.yebeh.2020.107003

Cited by 9 publications

(9 citation statements)

References 15 publications

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“…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

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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.

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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

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“…Los genes de mayor interés incluyen el SCN1A y ABCB1, que codifican Pgp. Sin embargo, aún no hay variantes genéticas comunes asociadas con farmacorresistencia que puedan predecir este fenotipo; y se habla de que los pacientes con epilepsia resistente a fármacos pueden ser por variantes raras, las cuales pueden tener complejidades que hay que tomar en cuenta, como cambios en genoma órgano-específicos (mutaciones somáticas) y variaciones regionales órgano-específicas (microheterogeneidad espacial), las cuales aún no se han explorado (14,(20)(21)(22)(23) .…”

Section: Hipótesis De Variantes De Genesunclassified

Epilepsia resistente a fármacos: definición y mecanismos

Sequeira-Quesada

Céspedes-Valverde

Delgado-Gómez

et al. 2023

Rev Hisp Cienc Salud

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La epilepsia es una enfermedad crónica que se caracteriza por crisis epilépticas recurrentes no provocadas debido a un aumento aberrante o a la sincronización de un grupo de neuronas. La epilepsia resistente a fármacos es cuando a pesar de utilizar dos o más fármacos en su dosis terapéutica, la persona sigue teniendo crisis recurrentes, esto afecta aproximadamente a un tercio de los pacientes. Existen múltiples hipótesis de mecanismos de resistencia, usualmente son variables y multifactoriales. Se puede dividir en tres grupos: mecanismos relacionados con la enfermedad, mecanismos relacionados a los fármacos y mecanismos genéticos. Aún faltan muchos estudios por realizar para comprender de una mejor manera estos mecanismos y generar diferentes propuestas de tratamiento.

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“…2,3 Drug-resistant epilepsy, which refers to the inability to fully control seizures with medication, affects approximately 1/3 of all patients with epilepsy, and 10 -30% of children patients. 4,5 Thus far, most studies have used adult epilepsy patient tissues, and much less are known about the alterations associated with epilepsy genesis in children. Since poorly controlled seizure severely affects the development and health of children, better treatments based on a deeper understanding of the cellular and molecular alterations in pediatric populations are of high importance.…”

Section: Introductionmentioning

confidence: 99%

Prominent contributions of selective neuronal subtypes to pediatric drug-resistant focal dysplasia

Zhang

Lin

Zhu

et al. 2023

Preprint

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About 75% cases of epilepsy begin during childhood, and 10 - 30% of pediatric epilepsy patients are resistant to drug treatment. The predominant seizure type in children is focal cortical dysplasia (FCD) which is highly associated with drug-resistant epilepsy, but its underlying cause is poorly understood. We performed single-cell RNA sequencing and patch-clamp recording on fresh brain tissues obtained from pediatric FCD patients shortly after surgery to reveal critical factors contributing to FCD. We report that known epilepsy genes or significant transcriptomic alterations occur in only a few neuronal subgroups, suggesting that epilepsy-associated neurons cluster into only a few neuronal subtypes. These epilepsy-subtypes displayed significant epilepsy-related transcriptomic alterations, especially in the genes associated with excitation/inhibition balance and neuron functional signal pathways. Among eight epilepsy-subtypes, L2_4_CUX2_YWHAH and PVALB_RGS5 subtypes showed the most prominent alterations in FCD patient tissues. Supporting PV-neurons being important, recording from fast-spiking/parvalbumin-containing neurons in acute FCD patient brain slices revealed reduced excitatory synaptic inputs, implicating lower activity in these neurons and fewer synaptic inputs onto them. A higher percentage of mitochondria genes, and likely higher activity in the pathways associated with oxidative phosphorylation and ATP biosynthetic process, was observed in the epilepsy-subtypes, suggesting a high energy expenditure in them. Interestingly, the activity of the above two pathways in most epilepsy-subtypes was lower in the FCD patients, suggesting these subtypes may be more vulnerable to energy deficit in epilepsy. Altogether, transcriptomics is significantly altered in only a few neuronal subtypes in pediatric FCD patient brains. These selective epilepsy-subtypes may play prominent roles in the genesis of pediatric drug-resistant seizure and targeting them may provide new treatment options.

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The role of targeted gene panel in pediatric drug-resistant epilepsy

Cited by 9 publications

References 15 publications

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

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

Epilepsia resistente a fármacos: definición y mecanismos

Prominent contributions of selective neuronal subtypes to pediatric drug-resistant focal dysplasia

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