Ophthalmic manifestations of MEPAN syndrome.

Background: Mitochondrial enoyl CoA reductase protein-associated neurodegeneration (MEPAN) syndrome is an ultra-rare autosomal recessive disorder caused by loss-of-function mutations in the MECR gene. The syndrome is characterized by dystonia in early childhood, basal ganglia signal abnormalities on MRI, and subsequent optic atrophy, with relative sparing of cognition. We characterize the ophthalmic manifestations observed in a patient with MEPAN syndrome, as a detailed account of ocular findings has not been published to date.

Methods: Case study of a patient with genetically confirmed MEPAN syndrome, with full ophthalmic evaluation including slit-lamp exam, sensorimotor exam, fundus photography, retinal ocular coherence tomography (OCT), electroretinography, visual evoked potentials, and visual field testing.

Results: The patient exhibited decreased visual acuity of 20/150 in both eyes with moderate dyschromatopsia on pseudoisochromatic plate testing, while peripheral vision was largely intact on Goldmann visual field testing. Fundus exam revealed bilateral optic atrophy with pallor most pronounced temporally, corresponding to OCT findings of diffuse retinal nerve fiber layer thinning most prominent in the papillomacular bundle region and severe ganglion cell layer thinning in the maculae. She also displayed a high frequency horizontal end-gaze nystagmus and symmetric bilateral external ophthalmoplegia.

Conclusions: The pattern of bilateral optic atrophy in our patient with MEPAN syndrome shows predilection for the papillomacular bundle, similar to that seen in other mitochondrial disorders with optic neuropathy, such as Leber Hereditary Optic Neuropathy and Dominant Optic Atrophy. Our patient's external ophthalmoplegia is another neuro-ophthalmic finding that may be seen in patients with heritable mitochondrial disease, either as an isolated ocular phenotype or within a constellation of systemic manifestations.