Targeted gene panel and genotype-phenotype correlation in children with developmental and epileptic encephalopathy

Ara Ko, Song Ee Youn, Se Hee Kim, Joon Soo Lee, Sangwoo Kim, Jong Rak Choi, Heung Dong Kim, Seung Tae Lee, Hoon Chul Kang

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Objective: We performed targeted gene-panel sequencing for children with developmental and epileptic encephalopathy (DEE) and evaluated the clinical implications of genotype–phenotype correlations. Methods: We assessed 278 children with DEE using a customized gene panel that included 172 genes, and extensively reviewed their clinical characteristics, including therapeutic efficacy, according to genotype. Results: In 103 (37.1%) of the 278 patients with DEE, 35 different disease-causing monogenic mutations were identified. The diagnostic yield was higher among patients who were younger at seizure onset, especially those whose seizures started during the neonatal period, and in patients with drug-resistant epilepsy. According to epilepsy syndromes, the diagnostic yield was the highest among patients with West syndrome (WS) with a history of neonatal seizures and mutations in KCNQ2 and STXBP1 were most frequently identified. On the basis of genotypes, we evaluated the clinical progression and seizure outcomes with specific therapeutic regimens; these were similar to those reported previously. In particular, sodium channel blockers were effective in patients with mutations in KCNQ2 and SCN2A in infancy, as well as SCN8A, and interestingly, the ketogenic diet also showed diverse efficacy for patients with SCN1A, CDKL5, KCNQ2, STXBP1, and SCN2A mutations. Unfortunately, quinidine was not effective in 2 patients with migrating focal epilepsy in infancy related to KCNT1 mutations. Conclusion: Targeted gene-panel sequencing is a useful diagnostic tool for DEE in children, and genotype–phenotype correlations are helpful in anticipating the clinical progression and treatment efficacy among these patients.

Original languageEnglish
Pages (from-to)48-55
Number of pages8
JournalEpilepsy Research
Volume141
DOIs
Publication statusPublished - 2018 Mar

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Genetic Association Studies
Brain Diseases
Genes
Seizures
Mutation
Genotype
Ketogenic Diet
Sodium Channel Blockers
Infantile Spasms
Quinidine
Partial Epilepsy
Epilepsy
Therapeutics

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

Cite this

Ko, Ara ; Youn, Song Ee ; Kim, Se Hee ; Lee, Joon Soo ; Kim, Sangwoo ; Choi, Jong Rak ; Kim, Heung Dong ; Lee, Seung Tae ; Kang, Hoon Chul. / Targeted gene panel and genotype-phenotype correlation in children with developmental and epileptic encephalopathy. In: Epilepsy Research. 2018 ; Vol. 141. pp. 48-55.
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abstract = "Objective: We performed targeted gene-panel sequencing for children with developmental and epileptic encephalopathy (DEE) and evaluated the clinical implications of genotype–phenotype correlations. Methods: We assessed 278 children with DEE using a customized gene panel that included 172 genes, and extensively reviewed their clinical characteristics, including therapeutic efficacy, according to genotype. Results: In 103 (37.1{\%}) of the 278 patients with DEE, 35 different disease-causing monogenic mutations were identified. The diagnostic yield was higher among patients who were younger at seizure onset, especially those whose seizures started during the neonatal period, and in patients with drug-resistant epilepsy. According to epilepsy syndromes, the diagnostic yield was the highest among patients with West syndrome (WS) with a history of neonatal seizures and mutations in KCNQ2 and STXBP1 were most frequently identified. On the basis of genotypes, we evaluated the clinical progression and seizure outcomes with specific therapeutic regimens; these were similar to those reported previously. In particular, sodium channel blockers were effective in patients with mutations in KCNQ2 and SCN2A in infancy, as well as SCN8A, and interestingly, the ketogenic diet also showed diverse efficacy for patients with SCN1A, CDKL5, KCNQ2, STXBP1, and SCN2A mutations. Unfortunately, quinidine was not effective in 2 patients with migrating focal epilepsy in infancy related to KCNT1 mutations. Conclusion: Targeted gene-panel sequencing is a useful diagnostic tool for DEE in children, and genotype–phenotype correlations are helpful in anticipating the clinical progression and treatment efficacy among these patients.",
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Targeted gene panel and genotype-phenotype correlation in children with developmental and epileptic encephalopathy. / Ko, Ara; Youn, Song Ee; Kim, Se Hee; Lee, Joon Soo; Kim, Sangwoo; Choi, Jong Rak; Kim, Heung Dong; Lee, Seung Tae; Kang, Hoon Chul.

In: Epilepsy Research, Vol. 141, 03.2018, p. 48-55.

Research output: Contribution to journalArticle

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AU - Youn, Song Ee

AU - Kim, Se Hee

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AU - Kim, Sangwoo

AU - Choi, Jong Rak

AU - Kim, Heung Dong

AU - Lee, Seung Tae

AU - Kang, Hoon Chul

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N2 - Objective: We performed targeted gene-panel sequencing for children with developmental and epileptic encephalopathy (DEE) and evaluated the clinical implications of genotype–phenotype correlations. Methods: We assessed 278 children with DEE using a customized gene panel that included 172 genes, and extensively reviewed their clinical characteristics, including therapeutic efficacy, according to genotype. Results: In 103 (37.1%) of the 278 patients with DEE, 35 different disease-causing monogenic mutations were identified. The diagnostic yield was higher among patients who were younger at seizure onset, especially those whose seizures started during the neonatal period, and in patients with drug-resistant epilepsy. According to epilepsy syndromes, the diagnostic yield was the highest among patients with West syndrome (WS) with a history of neonatal seizures and mutations in KCNQ2 and STXBP1 were most frequently identified. On the basis of genotypes, we evaluated the clinical progression and seizure outcomes with specific therapeutic regimens; these were similar to those reported previously. In particular, sodium channel blockers were effective in patients with mutations in KCNQ2 and SCN2A in infancy, as well as SCN8A, and interestingly, the ketogenic diet also showed diverse efficacy for patients with SCN1A, CDKL5, KCNQ2, STXBP1, and SCN2A mutations. Unfortunately, quinidine was not effective in 2 patients with migrating focal epilepsy in infancy related to KCNT1 mutations. Conclusion: Targeted gene-panel sequencing is a useful diagnostic tool for DEE in children, and genotype–phenotype correlations are helpful in anticipating the clinical progression and treatment efficacy among these patients.

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