Epilepsy Syndromes in the First Year of Life and Usefulness of Genetic Testing for Precision Therapy.
Epilepsy Syndromes in the First Year of Life and Usefulness of Genetic Testing for Precision Therapy.
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DOI：
10.3390/genes12071051
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发表时间：
2021-07-08
期刊：
影响因子：
3.5
通讯作者：
Møller RS
中科院分区：
文献类型：
--
作者：
Bayat A;Bayat M;Rubboli G;Møller RS
基因发现的快速发展导致癫痫遗传学领域取得了令人兴奋的进展。现在越来越多地使用全面的基因组、外显子组或基因组进行临床测试，这使得早发性癫痫的诊断率显着提高，并实现了精准医学方法。这些有助于深入了解早发性良性和自限性综合征以及破坏性发育性脑病和癫痫性脑病 (DEE) 的病理生理学。许多癫痫综合征中都存在遗传异质性，例如 West 综合征和婴儿期癫痫伴迁移性局灶性癫痫 (EIMFS)，表明两个或多个遗传位点产生相同或相似的表型。同时，一些基因（例如 SCN2A）可能与多种癫痫综合征相关，从轻度的自限性家族性新生儿癫痫到严重的大田原综合征、EIFMS、West 综合征、Lennox-Gastaut 综合征或无法分类的 DEE。本研究的目的是回顾与出生第一年开始的癫痫综合征相关的临床和遗传异质性，包括：自限性家族性新生儿、新生儿婴儿或婴儿癫痫、伴有热性惊厥+谱系的遗传性癫痫、婴儿期肌阵挛性癫痫、Ohtahara综合征、早期肌阵挛性脑病、West综合征、Dravet综合征、EIMFS和无法分类的DEE。我们还详细阐述了在这种情况下进行基因检测的优点和缺点。最后，我们描述了基因诊断如何能够实现单基因癫痫的精准治疗，并强调早期基因检测是此类治疗策略的基石。
The high pace of gene discovery has resulted in thrilling advances in the field of epilepsy genetics. Clinical testing with comprehensive gene panels, exomes, or genomes are now increasingly available and have led to a significant higher diagnostic yield in early-onset epilepsies and enabled precision medicine approaches. These have been instrumental in providing insights into the pathophysiology of both early-onset benign and self-limited syndromes and devastating developmental and epileptic encephalopathies (DEEs). Genetic heterogeneity is seen in many epilepsy syndromes such as West syndrome and epilepsy of infancy with migrating focal seizures (EIMFS), indicating that two or more genetic loci produce the same or similar phenotypes. At the same time, some genes such as SCN2A can be associated with a wide range of epilepsy syndromes ranging from self-limited familial neonatal epilepsy at the mild end to Ohtahara syndrome, EIFMS, West syndrome, Lennox–Gastaut syndrome, or unclassifiable DEEs at the severe end of the spectrum. The aim of this study was to review the clinical and genetic heterogeneity associated with epilepsy syndromes starting in the first year of life including: Self-limited familial neonatal, neonatal-infantile or infantile epilepsies, genetic epilepsy with febrile seizures plus spectrum, myoclonic epilepsy in infancy, Ohtahara syndrome, early myoclonic encephalopathy, West syndrome, Dravet syndrome, EIMFS, and unclassifiable DEEs. We also elaborate on the advantages and pitfalls of genetic testing in such conditions. Finally, we describe how a genetic diagnosis can potentially enable precision therapy in monogenic epilepsies and emphasize that early genetic testing is a cornerstone for such therapeutic strategies.
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作者：
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通讯作者：
Mefford, Heather C
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