Background

Aicardi-Goutières syndrome (AGS) is a genetic interferonopathy characterized by early onset of severe neurological injury with intracranial calcifications, leukoencephalopathy, and systemic inflammation. Increasingly, a spectrum of neurological dysfunction and presentation beyond the infantile period is being recognized in AGS. The aim of this study was to characterize late-infantile and juvenile-onset AGS.

Methods

We conducted a multi-institution review of individuals with AGS who were older than one year at the time of presentation, including medical history, imaging characteristics, and suspected diagnoses at presentation.

Results

Thirty-four individuals were identified, all with pathogenic variants in RNASEH2B, SAMHD1, ADAR1, or IFIH1. Most individuals had a history of developmental delay and/or systemic symptoms, such as sterile pyrexias and chilblains, followed by a prodromal period associated with increasing symptoms. This was followed by an abrupt onset of neurological decline (fulminant phase), with a median onset at 1.33 years (range 1.00 to 17.68 years). Most individuals presented with a change in gross motor skills (97.0%), typically with increased tone (78.8%). Leukodystrophy was the most common magnetic resonance imaging finding (40.0%). Calcifications were less common (12.9%).

Conclusions

This is the first study to characterize the presentation of late-infantile and juvenile onset AGS and its phenotypic spectrum. Late-onset AGS can present insidiously and lacks classical clinical and neuroimaging findings. Signs of early systemic dysfunction before fulminant disease onset and loss of motor symptoms were common. We strongly recommend genetic testing when there is concern for sustained inflammation of unknown origins or changes in motor skills in children older than one year.

中文翻译：

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迟发性 Aicardi-Goutières 综合征：呈现临床特征的特征

背景

Aicardi-Goutières 综合征 (AGS) 是一种遗传性干扰素病，其特征是早期发生严重的神经损伤，伴有颅内钙化、白质脑病和全身炎症。在 AGS 中越来越多地认识到婴儿期以外的一系列神经功能障碍和表现。本研究的目的是描述晚期婴儿和青少年发病的 AGS。

方法

我们对就诊时超过 1 岁的 AGS 患者进行了多机构审查，包括病史、影像学特征和就诊时的疑似诊断。

结果

鉴定出 34 名个体，均具有RNASEH2B、SAMHD1、ADAR1或IFIH1的致病变异。大多数个体有发育迟缓和/或全身症状的病史，例如无菌性发热和冻疮，随后出现与症状增加相关的前驱期。随后是神经功能衰退的突然发作（暴发期），中位发作时间为 1.33 岁（范围 1.00 至 17.68 岁）。大多数人表现出粗大运动技能的变化（97.0%），通常是语气增加（78.8%）。白质营养不良是最常见的磁共振成像发现（40.0%）。钙化不太常见（12.9%）。

结论

这是第一项描述晚期婴儿和青少年发病的 AGS 及其表型谱的研究。迟发性 AGS 可隐匿出现，缺乏经典的临床和神经影像学表现。疾病暴发前的早期全身功能障碍和运动症状消失的迹象很常见。当担心一岁以上儿童出现不明原因的持续炎症或运动技能改变时，我们强烈建议进行基因检测。