Expanding the phenotypic spectrum of FGF12-epilepsy-does prompt precision therapy affect outcomes?

IF 5.3 2区医学 Q1 GENETICS & HEREDITY

NPJ Genomic Medicine Pub Date : 2026-05-25 DOI:10.1038/s41525-026-00581-0

Leo Arkush, Kristina Karandasheva, Frédérique Ouellet, Alissa M D'Gama, Beth Rosen Sheidley, Nicole S Y Liang, Vann Chau, Gregory Costain, Lacey Smith, Anoushka Alwis, Christin Eltze, Annapurna Poduri, Felice D'Arco, Josh Adams, Kristen Lee, Jaspal Singh, Alexander P Y Brown, Arjuna Nagendran, Ben Pode-Shakked, Michal Tzadok, Bruria Ben Zeev, Amy McTague

{"title":"Expanding the phenotypic spectrum of FGF12-epilepsy-does prompt precision therapy affect outcomes?","authors":"Leo Arkush, Kristina Karandasheva, Frédérique Ouellet, Alissa M D'Gama, Beth Rosen Sheidley, Nicole S Y Liang, Vann Chau, Gregory Costain, Lacey Smith, Anoushka Alwis, Christin Eltze, Annapurna Poduri, Felice D'Arco, Josh Adams, Kristen Lee, Jaspal Singh, Alexander P Y Brown, Arjuna Nagendran, Ben Pode-Shakked, Michal Tzadok, Bruria Ben Zeev, Amy McTague","doi":"10.1038/s41525-026-00581-0","DOIUrl":null,"url":null,"abstract":"Fibroblast growth factor-12 (FGF12) variants have been associated with developmental and epileptic encephalopathy (DEE) with evidence of modulation of voltage-gated sodium channels Nav1.2 and Nav1.6. We aim to expand the phenotypic spectrum of FGF12-related epilepsy with emphasis on precision therapy. We describe 12 patients: eight with neonatal onset seizures with the recurrent p.Arg52His (c.155 G > A) variant, two with a previously unreported p.Glu153Gly (c.458 A > G) variant, one with a p.Gly50Ser (c.148 G > A) variant, and one with a de novo whole-gene duplication. Atypical absence seizures were present in 5/12 patients. Brain MRI was normal in 10/12; one patient's MRIs showed progressive cerebellar atrophy, and one patient's MRI showed a hemispheric infarct. 8 patients promptly started on sodium channel blockers became seizure-free with good developmental outcomes while 4 developed DEE. In summary, we expand the phenotypic spectrum of FGF12-related epilepsy and discuss the role of early precision therapy in developmental and epilepsy outcomes.","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":" ","pages":""},"PeriodicalIF":5.3000,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13385693/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"NPJ Genomic Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41525-026-00581-0","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}

引用次数: 0

Abstract

Fibroblast growth factor-12 (FGF12) variants have been associated with developmental and epileptic encephalopathy (DEE) with evidence of modulation of voltage-gated sodium channels Na_v1.2 and Na_v1.6. We aim to expand the phenotypic spectrum of FGF12-related epilepsy with emphasis on precision therapy. We describe 12 patients: eight with neonatal onset seizures with the recurrent p.Arg52His (c.155 G > A) variant, two with a previously unreported p.Glu153Gly (c.458 A > G) variant, one with a p.Gly50Ser (c.148 G > A) variant, and one with a de novo whole-gene duplication. Atypical absence seizures were present in 5/12 patients. Brain MRI was normal in 10/12; one patient's MRIs showed progressive cerebellar atrophy, and one patient's MRI showed a hemispheric infarct. 8 patients promptly started on sodium channel blockers became seizure-free with good developmental outcomes while 4 developed DEE. In summary, we expand the phenotypic spectrum of FGF12-related epilepsy and discuss the role of early precision therapy in developmental and epilepsy outcomes.

查看原文本刊更多论文

扩大fgf12的表型谱——快速精确治疗会影响结果吗？

成纤维细胞生长因子-12 （FGF12）变异与发育性和癫痫性脑病（DEE）有关，有证据表明其调节电压门控钠通道Nav1.2和Nav1.6。我们的目标是扩大fgf12相关癫痫的表型谱，重点是精确治疗。我们描述了12例患者：8例新生儿癫痫发作伴复发性p.g arg52his （c.155 G > A）变异，2例既往未报道p.g glu153gly （c.458 A > G）变异，1例p.g gly50ser （c.148 G > A）变异，1例从头开始的全基因重复。5/12患者出现非典型失神发作。10/12脑MRI正常；一名患者的MRI显示进行性小脑萎缩，一名患者的MRI显示半球梗死。8例患者迅速开始使用钠通道阻滞剂后无癫痫发作，发育结果良好，4例发生DEE。总之，我们扩大了fgf12相关癫痫的表型谱，并讨论了早期精确治疗在发育和癫痫结局中的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

NPJ Genomic Medicine Biochemistry, Genetics and Molecular Biology-Molecular Biology

CiteScore

9.40

自引率

1.90%

发文量

审稿时长

17 weeks

期刊介绍： npj Genomic Medicine is an international, peer-reviewed journal dedicated to publishing the most important scientific advances in all aspects of genomics and its application in the practice of medicine. The journal defines genomic medicine as "diagnosis, prognosis, prevention and/or treatment of disease and disorders of the mind and body, using approaches informed or enabled by knowledge of the genome and the molecules it encodes." Relevant and high-impact papers that encompass studies of individuals, families, or populations are considered for publication. An emphasis will include coupling detailed phenotype and genome sequencing information, both enabled by new technologies and informatics, to delineate the underlying aetiology of disease. Clinical recommendations and/or guidelines of how that data should be used in the clinical management of those patients in the study, and others, are also encouraged.