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Abstract：
BACKGROUND: Aicardi-Goutières syndrome (AGS) is a rare genetic disorder characterized by microcephaly, white matter lesions, numerous intracranial calcifications, chilblain skin lesions and high levels of interferon-α (IFN-α) in the cerebrospinal fluid (CSF). However, ocular involvement is reported significantly less frequently.
METHODS: We present a case of a neonate with hypotrophy, microcephaly, frostbite-like skin lesions, thrombocytopenia, elevated liver enzymes and hepatosplenomegaly. Magnetic resonance imaging (MRI) of the brain showed multiple foci of calcification, white matter changes, cerebral atrophy, and atrophic dilatation of the ventricular system. The inflammatory parameters were not elevated, and the infectious etiology was excluded. Instead, elevated levels of IFN-α in the serum were detected. Based on the related clinical symptoms, imaging and test findings, the diagnosis of AGS was suspected. Genetic testing revealed two pathogenic mutations, c.490C>T and c.222del (novel mutation), in the three prime repair exonuclease 1 (TREX1) gene, confirming AGS type 1 (AGS1). An ophthalmologic examination of the child at 10 months of age revealed an impaired pupillary response to light, a corneal haze with Haab lines in the right eye (RE), pale optic nerve discs and neuropathy in both eyes (OU). The intraocular pressure (IOP) was 51 mmHg in the RE and 49 in the left eye (LE). The flash visual evoked potential (FVEP) showed prolonged P2 latencies of up to 125% in the LE and reduced amplitudes of up to approximately 10% OU. This girl was diagnosed with congenital glaucoma, and it was managed with a trabeculectomy with a basal iridectomy of OU, resulting in a reduction and stabilization in the IOP to 12 mmHg in the RE and 10 mmHg in the LE without any hypotensive eyedrops.
CONCLUSIONS: We present the clinical characteristics, electrophysiological and imaging findings, as well as the genetic test results of a patient with AGS1. Our case contributes to the extended ophthalmic involvement of the pathogenic c.490C>T and c.222del mutations in TREX1.
METHODS: We present a case of a neonate with hypotrophy, microcephaly, frostbite-like skin lesions, thrombocytopenia, elevated liver enzymes and hepatosplenomegaly. Magnetic resonance imaging (MRI) of the brain showed multiple foci of calcification, white matter changes, cerebral atrophy, and atrophic dilatation of the ventricular system. The inflammatory parameters were not elevated, and the infectious etiology was excluded. Instead, elevated levels of IFN-α in the serum were detected. Based on the related clinical symptoms, imaging and test findings, the diagnosis of AGS was suspected. Genetic testing revealed two pathogenic mutations, c.490C>T and c.222del (novel mutation), in the three prime repair exonuclease 1 (TREX1) gene, confirming AGS type 1 (AGS1). An ophthalmologic examination of the child at 10 months of age revealed an impaired pupillary response to light, a corneal haze with Haab lines in the right eye (RE), pale optic nerve discs and neuropathy in both eyes (OU). The intraocular pressure (IOP) was 51 mmHg in the RE and 49 in the left eye (LE). The flash visual evoked potential (FVEP) showed prolonged P2 latencies of up to 125% in the LE and reduced amplitudes of up to approximately 10% OU. This girl was diagnosed with congenital glaucoma, and it was managed with a trabeculectomy with a basal iridectomy of OU, resulting in a reduction and stabilization in the IOP to 12 mmHg in the RE and 10 mmHg in the LE without any hypotensive eyedrops.
CONCLUSIONS: We present the clinical characteristics, electrophysiological and imaging findings, as well as the genetic test results of a patient with AGS1. Our case contributes to the extended ophthalmic involvement of the pathogenic c.490C>T and c.222del mutations in TREX1.
摘要：
背景：Aicardi-Goutières综合征（AGS）是一种罕见的以小头畸形为特征的遗传性疾病，白质病变,大量颅内钙化,冻疮皮肤损伤和脑脊液（CSF）中高水平的干扰素-α（IFN-α）。然而,据报道，眼部受累的频率明显较低。
方法：我们介绍一例新生儿肥厚不足，小头畸形,冻伤样皮肤损伤,血小板减少症,肝酶升高和肝脾肿大。脑部磁共振成像（MRI）显示多个钙化灶，白质变化,脑萎缩,和心室系统的萎缩性扩张。炎症参数没有升高，排除了感染性病因。相反，检测到血清中IFN-α水平升高。根据相关临床症状，成像和测试结果，怀疑诊断为AGS.基因检测显示有两种致病突变,c.490C>T和c.222del（新突变），在三主要修复核酸外切酶1（TREX1）基因中，确认AGS类型1(AGS1)。对10个月大的儿童进行眼科检查，发现瞳孔对光的反应受损，右眼有Haab线的角膜雾霾（RE），双眼（OU）的浅色视神经盘和神经病变。RE的眼内压（IOP）为51mmHg，左眼（LE）为49mmHg。闪光视觉诱发电位（FVEP）在LE中显示出高达125％的延长的P2潜伏期，并降低了高达10％OU的幅度。这个女孩被诊断患有先天性青光眼，并通过小梁切除术和OU基底虹膜切除术来治疗，导致在没有任何低血压滴眼液的情况下，RE的IOP降低并稳定至12mmHg，LE的IOP稳定至10mmHg。
结论：我们介绍了临床特征，电生理和成像发现，以及AGS1患者的基因检测结果。我们的病例有助于TREX1中致病性c.490C>T和c.222del突变的扩展眼科受累。
方法：我们介绍一例新生儿肥厚不足，小头畸形,冻伤样皮肤损伤,血小板减少症,肝酶升高和肝脾肿大。脑部磁共振成像（MRI）显示多个钙化灶，白质变化,脑萎缩,和心室系统的萎缩性扩张。炎症参数没有升高，排除了感染性病因。相反，检测到血清中IFN-α水平升高。根据相关临床症状，成像和测试结果，怀疑诊断为AGS.基因检测显示有两种致病突变,c.490C>T和c.222del（新突变），在三主要修复核酸外切酶1（TREX1）基因中，确认AGS类型1(AGS1)。对10个月大的儿童进行眼科检查，发现瞳孔对光的反应受损，右眼有Haab线的角膜雾霾（RE），双眼（OU）的浅色视神经盘和神经病变。RE的眼内压（IOP）为51mmHg，左眼（LE）为49mmHg。闪光视觉诱发电位（FVEP）在LE中显示出高达125％的延长的P2潜伏期，并降低了高达10％OU的幅度。这个女孩被诊断患有先天性青光眼，并通过小梁切除术和OU基底虹膜切除术来治疗，导致在没有任何低血压滴眼液的情况下，RE的IOP降低并稳定至12mmHg，LE的IOP稳定至10mmHg。
结论：我们介绍了临床特征，电生理和成像发现，以及AGS1患者的基因检测结果。我们的病例有助于TREX1中致病性c.490C>T和c.222del突变的扩展眼科受累。
