Down syndrome (DS) is characterized by a collection of clinical features including intellectual disability, congenital malformations, and susceptibility to infections and autoimmune diseases. While the presence of an extra chromosome 21 is known to cause DS, the precise genetic annotation linked to specific clinical features is largely missing. However, there is growing evidence that two genes located on chromosome 21, IFNAR1 and IFNAR2, play an important role in disease pathogenesis. These genes encode the two subunits of the receptor for type I interferons (IFN-I), a group of potent antiviral and pro-inflammatory cytokines. Human monogenic diseases caused by uncontrolled IFN-I production and response have been well characterized, and they clinically overlap with DS but also have notable differences. Herein, we review the literature characterizing the role of IFN-I in DS and compare and contrast DS to other IFN-mediated conditions. The existing IFN-I literature serves as a rich resource for testable hypotheses to elucidate disease mechanisms in DS and is likely to open novel therapeutic avenues.

唐氏综合症 (DS) 的特点是一系列临床特征，包括智力障碍、先天性畸形以及对感染和自身免疫性疾病的易感性。虽然已知额外的 21 号染色体的存在会导致 DS，但与特定临床特征相关的精确遗传注释在很大程度上缺失。然而，越来越多的证据表明，位于 21 号染色体上的两个基因IFNAR1和IFNAR2，在疾病的发病机制中起重要作用。这些基因编码 I 型干扰素 (IFN-I) 受体的两个亚基，这是一组有效的抗病毒和促炎细胞因子。由不受控制的 IFN-I 产生和反应引起的人类单基因疾病已得到很好的表征，它们在临床上与 DS 重叠，但也有显着差异。在此，我们回顾了描述 IFN-I 在 DS 中作用的文献，并将 DS 与其他 IFN 介导的疾病进行了比较和对比。现有的 IFN-I 文献可作为可检验假设的丰富资源，以阐明 DS 中的疾病机制，并可能开辟新的治疗途径。