Targeted gene panel sequencing in early infantile onset developmental and epileptic encephalopathy

Na, Jihoon; Shin, Saeam; Yang, Donghwa; Kim, Borahm; Kim, Heung Dong; Kim, Sehee; Lee, Joon Soo; Choi, Jong Rak; Lee, Seung Tae; Kang, Hoon Chul

doi:10.1016/j.braindev.2020.02.004

Cited by 33 publications

(36 citation statements)

References 28 publications

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“…Because of the early age of onset and heterogeneity in the genotype and phenotype, it is difficult to identify several key phenotypic features of some of the genes responsible for EIEEs. We identified pathogenic variants in 34% of children with suspected genetic aetiology by NGS, which was similar to previous studies ( 8 , 9 ). Despite progress in EIEE genetic diagnosis, there is still a limit for diagnosis using a gene panel.…”

Section: Discussionsupporting

confidence: 90%

Gene and Phenotype Expansion of Unexplained Early Infantile Epileptic Encephalopathy

et al. 2021

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Objective: The genetic aetiology of epileptic encephalopathy (EE) is growing rapidly based on next generation sequencing (NGS) results. In this single-centre study, we aimed to investigate a cohort of Chinese children with early infantile epileptic encephalopathy (EIEE).Methods: NGS was performed on 50 children with unexplained EIEE. The clinical profiles of children with pathogenic variants were characterised and analysed in detail. Conservation analysis and homology modelling were performed to predict the impact of STXBP1 variant on the protein structure.Results: Pathogenic variants were identified in 17 (34%) of 50 children. Sixteen variants including STXBP1 (n = 2), CDKL5 (n = 2), PAFAH1B1, SCN1A (n = 9), SCN2A, and KCNQ2 were de novo, and one (PIGN) was a compound heterozygous variant. The phenotypes of the identified genes were broadened. PIGN phenotypic spectrum may include EIEE. The STXBP1 variants were predicted to affect protein stability.Significance: NGS is a useful diagnostic tool for EIEE and contributes to expanding the EIEE-associated genotypes. Early diagnosis may lead to precise therapeutic interventions and can improve the developmental outcome.

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Section: Discussionsupporting

confidence: 90%

Gene and Phenotype Expansion of Unexplained Early Infantile Epileptic Encephalopathy

et al. 2021

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“…This mutation has been previously reported multiple times as pathogenic, and in silico studies predicted it as deleterious. 2,[5][6][7][8][9] As a result, this mutation was classified as pathogenic. Parental segregation studies showed that both parents did not harbor the mutation; hence, this was a de novo mutation.…”

Section: Introductionmentioning

confidence: 99%

KCNQ2 Encephalopathy and Responsiveness to Pyridoxal-5′-Phosphate

Kwong

2020

J Pediatr Genet

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KCNQ2 mutations encompass a wide range of phenotypes, ranging from benign familial neonatal seizure to a clinical spectrum of early-onset epileptic encephalopathy that occurs in the early neonatal period. We report an infant with KCNQ2 encephalopathy presenting as neonatal seizure, initially controlled by two anticonvulsants. Electroencephalogram (EEG) showed repetitive multifocal epileptiform discharges, which remained similar after administration of intravenous pyridoxine injection. Seizure recurred at the age of 3 months preceded by an episode of minor viral infection, which occurred multiple times per day. No significant change in seizure frequency was observed after 5-day oral pyridoxine trial, but subsequently, there was dramatic seizure improvement with oral pyridoxal-5′-phosphate (PLP). We hope to alert clinicians that in patients with neonatal epileptic encephalopathy, particularly with known KCNQ2 mutations, intravenous injection of pyridoxine (preferably with EEG monitoring), followed by both oral trial of pyridoxine and PLP should be considered. KCNQ2 mutations should also be considered in vitamin B6-responsive patients.

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“…In previous studies, sodium-channel blockers, such as carbamazepine and phenytoin, were reported to be effective in pati ents with KCNQ2 encephalopathy 3,7,8,11) . Phenobarbital is the most commonly used antiepileptic drug for neonatal seizures, while carbamazepine is rarely used in neonates.…”

Section: Discussionmentioning

confidence: 99%

“…The development of gene sequencing techniques has led to an increasing identification of genetic causes for DEE 2) . Targeted gene panel testing revealed a diagnostic yield of 42.9% and 65.2 % in recent studies from South Korea and the United States, respectively 1,3) . Mutations in KCNQ2 are frequently identified in patients with DEE 1,3) are located on the chromosome (20q13.33) encoding the voltage-dependent potassium channel subunit 7.2 (Kv7.2), and manifest as a broad spectrum of neonatal-onset epilepsy with a varying severity from benign familial neonatal seizures to KCNQ2 encephalopathy [4][5][6] .…”

Section: Introductionmentioning

confidence: 98%

“…KCNQ2 encephalopathy is associated with refractory seizures resulting in a poor neurodevelopmental outcome. Many patients with DEE have seizures refractory to multiple antiepileptic drugs, while those with KCNQ2 encephalopathy reportedly have a positive response to sodium-channel blockers 3,7,8) . In other words, the early identification of KCNQ2 encephalopathy makes it a more direct therapeutic approach possible.…”

Section: Introductionmentioning

confidence: 99%

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KCNQ2 Encephalopathy Showing a Distinct Ictal Amplitude-Integrated Electroencephalographic Pattern

et al. 2020

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Targeted gene panel sequencing in early infantile onset developmental and epileptic encephalopathy

Cited by 33 publications

References 28 publications

Gene and Phenotype Expansion of Unexplained Early Infantile Epileptic Encephalopathy

Gene and Phenotype Expansion of Unexplained Early Infantile Epileptic Encephalopathy

KCNQ2 Encephalopathy and Responsiveness to Pyridoxal-5′-Phosphate

KCNQ2 Encephalopathy Showing a Distinct Ictal Amplitude-Integrated Electroencephalographic Pattern

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