Raffaele Falsaperla, Roberta Criscione, Carla Cimino, Francesco Pisani, Martino Ruggieri
{"title":"KCNQ2相关癫痫:基因型表型与特制抗癫痫药物(ASM)的关系——一项系统综述。","authors":"Raffaele Falsaperla, Roberta Criscione, Carla Cimino, Francesco Pisani, Martino Ruggieri","doi":"10.1055/a-2060-4576","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Autosomal dominant mutations of the <i>KCNQ2</i> gene can cause two epileptic disorders: benign familial neonatal seizures (BFNS) and developmental epileptic encephalopathy (DEE). This systematic review aims to identify the best reported therapy for these patients, relating to phenotype, neurodevelopmental outcome, and an eventual correlation between phenotype and genotype.</p><p><strong>Methods: </strong>We searched on PubMed using the search terms \"<i>KCNQ2</i>\" AND \"therapy\" and \"<i>KCNQ2</i>\" AND \"treatment\"; we found 304 articles. Of these, 29 met our criteria. We collected the data from 194 patients. All 29 articles were retrospective studies.</p><p><strong>Results: </strong>In all, 104 patients were classified as DEE and 90 as BFNS. After treatment began, 95% of BFNS patients became seizure free, whereas the seizures stopped only in 73% of those with DEE. Phenobarbital and sodium channel blockers were the most used treatment in BFNS. Most of the DEE patients (95%) needed polytherapy for seizure control and even that did not prevent subsequent developmental impairment (77%).Missense mutations were discovered in 96% of DEE patients; these were less common in BFNS (50%), followed by large deletion (16%), truncation (16%), splice donor site (10%), and frameshift (7%).</p><p><strong>Conclusion: </strong>Phenobarbital or carbamazepine appears to be the most effective antiseizure medication for children with a \"benign\" variant. On the contrary, polytherapy is often needed for DEE patients, even if it does not seem to improve neurological outcomes. In DEE patients, most mutations were located in S4 and S6 helix, which could serve as a potential target for the development of more specific treatment in the future.</p>","PeriodicalId":19421,"journal":{"name":"Neuropediatrics","volume":null,"pages":null},"PeriodicalIF":1.1000,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"KCNQ2-Related Epilepsy: Genotype-Phenotype Relationship with Tailored Antiseizure Medication (ASM)-A Systematic Review.\",\"authors\":\"Raffaele Falsaperla, Roberta Criscione, Carla Cimino, Francesco Pisani, Martino Ruggieri\",\"doi\":\"10.1055/a-2060-4576\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Autosomal dominant mutations of the <i>KCNQ2</i> gene can cause two epileptic disorders: benign familial neonatal seizures (BFNS) and developmental epileptic encephalopathy (DEE). This systematic review aims to identify the best reported therapy for these patients, relating to phenotype, neurodevelopmental outcome, and an eventual correlation between phenotype and genotype.</p><p><strong>Methods: </strong>We searched on PubMed using the search terms \\\"<i>KCNQ2</i>\\\" AND \\\"therapy\\\" and \\\"<i>KCNQ2</i>\\\" AND \\\"treatment\\\"; we found 304 articles. Of these, 29 met our criteria. We collected the data from 194 patients. All 29 articles were retrospective studies.</p><p><strong>Results: </strong>In all, 104 patients were classified as DEE and 90 as BFNS. After treatment began, 95% of BFNS patients became seizure free, whereas the seizures stopped only in 73% of those with DEE. Phenobarbital and sodium channel blockers were the most used treatment in BFNS. Most of the DEE patients (95%) needed polytherapy for seizure control and even that did not prevent subsequent developmental impairment (77%).Missense mutations were discovered in 96% of DEE patients; these were less common in BFNS (50%), followed by large deletion (16%), truncation (16%), splice donor site (10%), and frameshift (7%).</p><p><strong>Conclusion: </strong>Phenobarbital or carbamazepine appears to be the most effective antiseizure medication for children with a \\\"benign\\\" variant. On the contrary, polytherapy is often needed for DEE patients, even if it does not seem to improve neurological outcomes. In DEE patients, most mutations were located in S4 and S6 helix, which could serve as a potential target for the development of more specific treatment in the future.</p>\",\"PeriodicalId\":19421,\"journal\":{\"name\":\"Neuropediatrics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.1000,\"publicationDate\":\"2023-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neuropediatrics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1055/a-2060-4576\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/3/22 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuropediatrics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1055/a-2060-4576","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/3/22 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Background: Autosomal dominant mutations of the KCNQ2 gene can cause two epileptic disorders: benign familial neonatal seizures (BFNS) and developmental epileptic encephalopathy (DEE). This systematic review aims to identify the best reported therapy for these patients, relating to phenotype, neurodevelopmental outcome, and an eventual correlation between phenotype and genotype.
Methods: We searched on PubMed using the search terms "KCNQ2" AND "therapy" and "KCNQ2" AND "treatment"; we found 304 articles. Of these, 29 met our criteria. We collected the data from 194 patients. All 29 articles were retrospective studies.
Results: In all, 104 patients were classified as DEE and 90 as BFNS. After treatment began, 95% of BFNS patients became seizure free, whereas the seizures stopped only in 73% of those with DEE. Phenobarbital and sodium channel blockers were the most used treatment in BFNS. Most of the DEE patients (95%) needed polytherapy for seizure control and even that did not prevent subsequent developmental impairment (77%).Missense mutations were discovered in 96% of DEE patients; these were less common in BFNS (50%), followed by large deletion (16%), truncation (16%), splice donor site (10%), and frameshift (7%).
Conclusion: Phenobarbital or carbamazepine appears to be the most effective antiseizure medication for children with a "benign" variant. On the contrary, polytherapy is often needed for DEE patients, even if it does not seem to improve neurological outcomes. In DEE patients, most mutations were located in S4 and S6 helix, which could serve as a potential target for the development of more specific treatment in the future.
期刊介绍:
For key insights into today''s practice of pediatric neurology, Neuropediatrics is the worldwide journal of choice. Original articles, case reports and panel discussions are the distinctive features of a journal that always keeps abreast of current developments and trends - the reason it has developed into an internationally recognized forum for specialists throughout the world.
Pediatricians, neurologists, neurosurgeons, and neurobiologists will find it essential reading.