Aicardi-Goutières Syndrome with Congenital Glaucoma Caused by Novel TREX1 Mutation

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.

Case presentation: 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.

Keywords: Aicardi–Goutières syndrome; TREX1; congenital glaucoma; interferon alpha; type 1 interferonopathies.

Figure 1

Photography of the RE fundus, obtained during examination under general anesthesia, showed an enlarged cup-to-disc ratio, nasal shifting of blood vessels and pallor of the remaining neuro-retinal rim.

Figure 2

Trabeculectomy with basal iridectomy in the RE: (A) preparation of the superficial scleral flap (limbal-based flap, 4 mm × 3 mm); (B) determination of the size of the deep scleral flap; (C) dissection of the deep scleral flap (1.5 mm × 2 mm); (D) punctate opening of the anterior chamber; (E) excision of the deep scleral flap; (F) basal iris excision; (G) inspection of the created fistula; (H) superficial flap suture placement.

Figure 3

Photography of a patient at the age of 3 years. There is apparent small neurocranium, oval face and fairly large auricles; forehead is slightly posteriorly tilted; fine, short hair with V-shaped line on head; mouth with narrow red lips.