Unilateral morning glory disc anomaly in a patient with prenatal Zika virus exposure

Background To report a case of morning glory disc anomaly (MGDA) in a pediatric patient with prenatal Zika virus (ZIKV) exposure. Case presentation A 3-year-old male with prenatal exposure to ZIKV, confirmed by real-time polymerase chain reaction testing during the second trimester of pregnancy, was evaluated due to visual loss. Physical examination was remarkable for unilateral MGDA. Neuroimaging showed a base of skull encephalocele through the floor of the sella and callosal dysgenesis. Conclusions This is the first report to suggest an association between prenatal ZIKV exposure and MGDA. Prenatal ZIKV exposure may be associated to a wider pathologic spectrum than previously reported.


Introduction
Morning glory disc anomaly (MGDA) is a rare congenital anomaly of the optic disc and peripapillary retina [1,2]. The prevalence of MGDA has been estimated to be approximately 2.6/100,000 [3]. Characteristic findings include an enlarged optic disc with a central funnelshaped excavation, a hypopigmented central tuft of glial tissue, peripapillary chorioretinal atrophy, and radial spoke-like vascular pattern [1,2,4,5]. MGDA is sporadic, exhibits female predominance, and is typically unilateral [1,4,6,7]. MGDA has also been associated with midline craniofacial defects [1,6]. Central visual acuity may be normal or decreased, depending on the extent of the disease [7].

Case report
A 3-year-old male child with a previous medical history of strabismus and cleft lip was referred to our clinics due to an anomalous optic disc and visual loss. Perinatal history revealed that during the second trimester of pregnancy the mother developed a generalized maculopapular rash. The mother denied having any other symptoms including headache, fever, conjunctivitis, arthralgia, or myalgia. Due to her symptoms, the mother underwent a real-time polymerase chain reaction (RT-PCR) test for ZIKV with positive results. Postnatal history was remarkable for a 4 day hospitalization at the neonatal intensive care unit (NICU) due to hyperbilirubinemia treated with phototherapy. Previous ocular history was remarkable for decreased visual acuity in the right eye (OD) with sensory exotropia diagnosed at 11 months of age. Strabismus surgery had been undertaken after unsuccessful occlusion therapy with excellent anatomical outcomes.
A complete ophthalmological exam was performed. Best-corrected visual acuity was 20/200 OD and 20/20 in the left eye (OS). Intraocular pressure was normotensive in both eyes (OU). No nystagmus was present. Extraocular muscle ductions were full, but a small angle exotropia was present OD. Pupils were equally round and with an afferent pupillary defect OD. The anterior segment was unremarkable OU.
Posterior segment examination showed a centrally excavated optic disc with associated hypopigmented glial tuft, peripapillary chorioretinal atrophy, and radial spoke-like vascular pattern consistent with MGDA OD (Fig. 1). No foveal reflex was present OD. The OS posterior segment was unremarkable (Fig. 1).
Magnetic resonance imaging (MRI) and computed tomography (CT) were performed and were remarkable for a base of skull encephalocele and callosal dysgenesis. The pituitary gland, infundibulum and optic chiasm were not well visualized raising concern for other associated midline developmental abnormalities (Fig. 2).

Discussion and conclusions
MGDA is part of a spectrum of diseases affecting the optic disc known as excavated optic disc anomalies, which also include peripapillary staphyloma, optic disc coloboma, optic disc pit, megalopapilla, and optic disc dysplasia [18]. The pathophysiological mechanisms leading to the spectrum of excavated optic disc anomalies continue to be incompletely understood [18,19]. We report the first case of MGDA after confirmed prenatal ZIKV exposure. It is possible that ZIKV infection may alter intrauterine optic nerve development and lead to MGDA.
Van den Pol and associates [20] have theorized that after ZIKV is vertically transmitted, it may invade the cortical progenitor cells inside the fetal brain. The virus may then infect, via axonal transport, other parts of the visual system including the retina, optic chiasm,  T2 (a and b), sagittal post-contrast T1 (c) weighted images, and sagittal non-contrast CT (d) of the brain through midline demonstrate a bony defect at the floor of the sella with herniation of cerebrospinal fluid through the defect into the sphenoid sinuses consistent with a base of skull encephalocele. There is also evidence of absence of the distal body, splenium, and rostrum of the corpus callosum consistent with callosal dysgenesis. The pituitary gland, infundibulum, and optic chiasm were not well visualized raising concern for other associated midline developmental abnormalities suprachiasmatic nucleus, and superior colliculus [9,20]. Some histologic studies have suggested that glial cells within the optic chiasm and optic tract may be an important target of the ZIKV [9,20]. To support this hypothesis, Fernandez et al. performed a histopathological evaluation of four deceased fetuses and isolated ZIKV from the optic nerve, neural retina, and choroid [21]. The intracranial anomalies that have been associated to MGDA overlap with those reported in some cases of CZS. It is possible that early glial cell dysfunction inside the optic nerve may lead to MGDA. Future studies may determine the exact mechanisms that lead to MGDA. To our knowledge, this is the first study to report a case of MGDA in a patient with prenatal ZIKV exposure. The rarity MGDA may explain the lack of previous reports among children with prenatal ZIKV exposure [22,23]. Although our report cannot demonstrate a causal relationship between prenatal ZIKV exposure and MGDA, their association should be explored in future research studies. This report suggests that prenatal exposure to ZIKV may lead to a wider pathological spectrum than previously described.