Abdel-Salam Ghada M H, Abdel-Hamid Mohamed S, Mohammad Shaimaa A, Abdel-Ghafar Sherif F, Soliman Doaa R, El-Bassyouni Hala T, Effat Laila, Zaki Maha S
Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
Medical Molecular Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
Metab Brain Dis. 2017 Jun;32(3):679-683. doi: 10.1007/s11011-017-9993-4. Epub 2017 Mar 23.
Aicardi-Goutières syndrome (AGS) is one of the expanding group of inherited congenital infection like syndromes. Here, we describe the detailed clinical and imaging findings of two sibs with AGS. Each shows scattered periventricular intracranial calcifications, severe global delay, seizures, microcephaly and spasticity. Interestingly, chilblains were observed in the two sisters as well as their parents and a paternal uncle. The brain MRI of the older sister showed marked ventricular dilatation as a result of unusual associated porencephalic cysts. Unexpectedly, unilateral cerebellar hypoplasia was also noted. In comparison, her younger sister displayed the classic atrophic changes and white matter loss of AGS. The diagnosis of AGS was confirmed by sequence analysis, which identified a previously reported homozygous RNASEH2B mutation, c.554 T > G (p.V185G). Parents were heterozygous for the same mutation. Further molecular analysis excluded mutations in potentially related manifestations of COL4A1 gene. This is the first report of chilblains associated with heterozygous RNASEH2B mutation. Further, the brain imaging findings appear particularly interesting, which until now has not been reported in any AGS patient. We discuss the possible reasons for this unusual presentation.
艾卡迪-古铁雷斯综合征（AGS）是一类不断增多的遗传性先天性感染样综合征之一。在此，我们描述了两名患有AGS的同胞的详细临床和影像学表现。两人均有散在的脑室周围颅内钙化、严重的全面发育迟缓、癫痫发作、小头畸形和痉挛。有趣的是，在这两名姐妹及其父母和一位叔祖父身上均观察到冻疮。姐姐的脑部MRI显示，由于伴有异常的脑穿通性囊肿，脑室明显扩张。出乎意料的是，还发现了单侧小脑发育不全。相比之下，妹妹表现出AGS典型的萎缩性改变和白质丢失。通过序列分析确诊为AGS，该分析鉴定出一个先前报道的纯合RNASEH2B突变，即c.554 T>G（p.V185G）。父母为该相同突变的杂合子。进一步的分子分析排除了COL4A1基因潜在相关表现中的突变。这是与杂合RNASEH2B突变相关的冻疮的首次报道。此外，脑部影像学表现显得尤为有趣，迄今为止尚未在任何AGS患者中报道过。我们讨论了这种异常表现的可能原因。
