基因检测阴性或不确定后的发展性和癫痫性脑病:下一步是什么?

Á. Aledo-Serrano, R. Sánchez‐Alcudia, R. Toledano, I. García-Morales, Á. Beltrán-Corbellini, Isabel del Pino, A. Gil-Nagel
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引用次数: 6

摘要

经典电临床综合征的重新定义和神经遗传学的出现导致了发育性和癫痫性脑病(dee)领域的革命。在这种情况下,遗传技术的进步正在导致很大比例的DEE患者的最终诊断。然而,高达50%的DEE患者仍未得到诊断。对于遗传病因不确定的患者,迫切需要实施新的靶向治疗和精准医疗。在一些未确诊的患者中,进一步深入或反向表型的基因再分析是有价值的诊断工具,以澄清不确定意义的新变异。在其他情况下,需要实施新的生物信息学算法来更新和重新评估以前生成的遗传数据。此外,已经开发了许多其他临床工具,用于管理阴性或不确定基因检测后的dei患者。在这篇综述中,我们强调了用于没有已知遗传病因的DEE患者的新诊断策略的进展和局限性。最后,我们对需要进一步研究的方面提供了广泛的视角,特别是在非孟德尔遗传方面,例如与中枢神经系统的体细胞嵌合体或表观遗传和少生机制有关的研究。
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Developmental and epileptic encephalopathies after negative or inconclusive genetic testing: what is next?
The redefinition of classical electroclinical syndromes and the emergence of neurogenetics has led to a revolution in the field of developmental and epileptic encephalopathies (DEEs). In this context, advances in genetic techniques are leading to the final diagnosis of a large proportion of patients with DEE. However, up to 50% of patients with DEE remain undiagnosed. For patients with uncertain genetic etiology, there is a pressing need for the implementation of new targeted treatments and precision medicine. In some undiagnosed patients, genetic reanalysis with further in-depth or reverse phenotyping are valuable diagnostic tools to clarify new variants of uncertain significance. In other cases, the implementation of new bioinformatic algorithms is required for the update and reassessment of previously generated genetic data. Moreover, many other clinical tools have been developed for the management of patients of DEEs after a negative or inconclusive genetic testing. In this review, we highlight advances and limitations of new diagnostic strategies used in DEE patients without a known genetic etiology. Finally, we provide a wide perspective on aspects that will need further research, especially in non-Mendelian inheritance DEEs, such as those related to somatic mosaicism of the central nervous system or epigenetic and oligogenic mechanisms.
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