Multiple Retinal Holes and Peripheral Nonperfusion in Muscle-Eye-Brain Disease

Muscle-eye-brain (MEB) disease is a rare congenital autosomal recessive disorder with around 30 reported cases in the literature.^1,2 It is 1 of 3 types of congenital muscular dystrophy with severe defects in organogenesis and neuronal migration, and, along with Walker-Warburg syndrome, is associated with ocular abnormalities.³ Usually, the retina in MEB disease and Walker-Warburg syndrome is described as dysplasic.⁴ A detailed histopathologic description has been given,⁵ but a clinical description of retinal findings, especially in early disease, is lacking. Herein, we describe detailed retinal findings in a neonate with the diagnosis of MEB disease confirmed by genetic testing.

A 12-day-old girl who was born full term was referred owing to a suspected retinal detachment in the right eye noted soon after birth. Her neonatal history was significant for an endoscopic third ventriculostomy at 1 day of life for hydrocephalus after magnetic resonance imaging revealed severe brain and brainstem malformation with an absent corpus callosum, cortical gyral thickening, cerebellar vermian hypoplasia, and markedly enlarged lateral and third ventricles (Figure 1). Examination under anesthesia disclosed unremarkable anterior segment examination results in both eyes. Posterior segment examination of the right eye revealed a retinal detachment that obscured the optic nerve and fovea, but with a bullous elevation in a nearby macular area and superior elevated fibrosis (Figure 2A). Closer examination of the peripheral detachment revealed an avascular retina with multiple lacunae and full-thickness holes (Figure 2B). Posterior examination of the left eye revealed moderate optic nerve hypoplasia, an indistinct but attached fovea, and an anomalous distribution of vessels with very reduced caliber to vessels coursing superiorly, which appeared to terminate in the equatorial zone (Figure 3). The periphery of the left eye was featureless with poor pigmentation and an impressive extent of visible choroidal vasculature.

Fluorescein angiography of the right eye revealed leakage from the fibrosis, indicative of extraretinal fibrovascular proliferation (Figure 4). Fluorescein angiography of the left eye showed a hypoplastic retina with prominent choroidal flush and anomalous vasculature that terminated in the equatorial zone (Figure 5). Prophylactic laser treatment was performed in each eye in areas of nonperfusion, and pars plana vitrectomy, lensectomy, and silicone oil placement were performed in the right eye.

Subsequent genetic testing revealed a POMGnT1 mutation, consistent with MEB disease.³ Specifically, the mutation was in POMGnT1 intron 17. This resulted in a DNA substitution of c1539 + 1 G>A, which is a common founder mutation in Finnish patients.⁶ Mutations in POMGnT1 near the 5′ terminus, as is the case with c1539 + 1 G>A, have been suggested to correlate with more severe cerebral malformations.⁶

Both MEB disease and Walker-Warburg syndrome have underlying deficiencies in posttranslational glycosylation of α-dystroglycan³ that lead to severe defects in organogenesis and neuronal migration. Brain and eye phenotypes in MEB disease and Walker-Warburg syndrome likely involve defective glycosylation in proteins other than α-dystroglycan since chimeric mice deficient in α-dystroglycan develop congenital muscular dystrophy but not brain or eye phenotypes of MEB disease or Walker-Warburg syndrome.⁷ In both diseases, there can be hypoplasia of the retina, choroid, optic nerve, and iris.^1,2,8 Specifically, Zervos et al⁵ performed a histopathologic examination of 2 siblings with MEB disease and found loss of the inner nuclear layer, thinning of the outer nuclear layer, absence of rod and cone outer segments in midperipheral portions of the retina, and localized nerve fiber layer schisis nasal to the optic nerve head. They also noted focally atrophic retinal pigment epithelium and diffuse choroidal atrophy.⁵

In our patient, with genetic testing results supportive of an MEB disease diagnosis, we describe the previously unreported clinical findings in early disease. A peripheral avascular retina led to extraretinal fibrovascular proliferation with subsequent contracture and combined tractional and rhegmatogenous retinal detachment with multiple perforating holes in the right eye. The underlying defect in glycosylation in MEB disease, which results in a severe defect in neuronal migration and possibly in hypoplasia of various structures, may be the cause of these retinal findings.

Correspondence: Dr Shapiro, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855 W Taylor St, M/C 648, Chicago, IL 60612 (michaelj.shapiro@gmail.com).

Author Contributions: Dr Shapiro had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Financial Disclosure: None reported.

Funding/Support: This work was supported by an unrestricted grant from Research to Prevent Blindness, New York, New York (Dr Blair).