Genetic and biologic classification of infantile spasms.
Genetic and biologic classification of infantile spasms.
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DOI：
10.1016/j.pediatrneurol.2011.08.010
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发表时间：
2011-12
影响因子：
3.8
通讯作者：
Dobyns WB
中科院分区：
文献类型：
--
作者：
Paciorkowski AR;Thio LL;Dobyns WB
婴儿痉挛是一种年龄依赖性癫痫，与认知障碍、自闭症和运动障碍高度相关。以前的分类系统侧重于症状性和隐源性病因的区分，并没有跟上最近发现的婴儿痉挛患者中枢神经系统发育关键通路基因突变的步伐。患有某些遗传综合征的儿童更有可能患有婴儿痉挛，我们回顾了文献，提出了这些疾病的遗传分类。与婴儿痉挛有这些遗传关联的儿童也有癫痫以外的表型，这可以通过最近对潜在生物学机制的理解来解释。因此，我们也提出了与婴儿痉挛高度相关的基因的生物学分类，并基于该数据阐明了婴儿痉挛发病机制的模型。两种最好的发病途径是gaba能前脑发育基因调控网络的异常和突触表达分子的异常。我们希望这些遗传和生物学分类是灵活的，并希望它们将鼓励在综合征识别，临床基因检测方面取得急需的进展，并最终开发针对特定发病途径的新疗法。
Infantile spasms are an age-dependent epilepsy that are highly associated with cognitive impairment, autism, and movement disorders. Previous classification systems have focused on a distinction between symptomatic and cryptogenic etiologies, and have not kept pace with the recent discoveries of mutations in genes in key pathways of central nervous system development in patients with infantile spasms. Children with certain genetic syndromes are much more likely to have infantile spasms, and we review the literature to propose a genetic classification of these disorders. Children with these genetic associations with infantile spasms also have phenotypes beyond epilepsy that may be explained by recent advances in the understanding of underlying biological mechanisms. We therefore also propose a biologic classification of the genes highly associated with infantile spasms, and articulate models for infantile spasms pathogenesis based on that data. The two best described pathways of pathogenesis are abnormalities in the gene regulatory network of GABAergic forebrain development, and abnormalities in molecules expressed at the synapse. We intend for these genetic and biologic classifications to be flexible, and hope that they will encourage much needed progress in syndrome recognition, clinical genetic testing, and ultimately the development of new therapies that target specific pathways of pathogenesis.
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