Arberas Claudia, Ruggieri Víctor
Sección Genética Médica, Hospital de Niños Dr. Ricardo Gutiérrez, Buenos Aires.
Medicina (B Aires). 2013;73 Suppl 1:20-9.
Autism spectrum disorders are characterized by impairment of social integration and language development and restricted interests. Autism spectrum disorders manifest during childhood and may have a varying clinical expression over the years related to different therapeutic approaches, behavior-modifying drugs, and environmental factors, among others. So far, the genetic alterations identified are not sufficient to explain the genesis of all these processes, as many of the mutations found are also present in unaffected individuals. Findings on the underlying biological and pathophysiological mechanisms of entities strongly associated with autism spectrum disorders, such as Rett, fragile X, Angelman, and fetal alcohol syndromes, point to the role of epigenetic changes in disorders of neurodevelopment. Epigenetic phenomena are normal biological processes necessary for cell and thus human life, especially related to embryonic development. Different phenomena that affect epigenetic processes (changes that change operation or expression of a gene, without modifying the DNA structure) have also been shown to be important in the genesis of neurodevelopmental disorders. Alterations in the epigenetic mechanism may be reversible, which may explain the variation in the autism phenotype over time. Here we analyze the normal epigenetic mechanisms, autism spectrum disorders, their association with specific entities associated with altered epigenetic mechanisms, and possible therapeutic approaches targeting these alterations.
自闭症谱系障碍的特征是社交整合和语言发展受损以及兴趣受限。自闭症谱系障碍在儿童期出现，多年来可能因不同的治疗方法、行为修正药物和环境因素等而有不同的临床表型。到目前为止，已确定的基因改变不足以解释所有这些过程的发生，因为许多发现的突变也存在于未受影响的个体中。与自闭症谱系障碍密切相关的疾病，如雷特综合征、脆性X综合征、天使综合征和胎儿酒精综合征，其潜在生物学和病理生理机制的研究结果表明表观遗传变化在神经发育障碍中起作用。表观遗传现象是细胞乃至人类生命所必需的正常生物学过程，尤其与胚胎发育有关。影响表观遗传过程的不同现象（改变基因操作或表达而不改变DNA结构的变化）在神经发育障碍的发生中也很重要。表观遗传机制的改变可能是可逆的，这可以解释自闭症表型随时间的变化。在此，我们分析正常的表观遗传机制、自闭症谱系障碍、它们与表观遗传机制改变相关的特定疾病的关联，以及针对这些改变的可能治疗方法。
