Ocular phenotype and electroretinogram abnormalities in Lafora disease

Lafora disease (LD) is a teenage-onset progressive neurologic disorder caused by biallelic mutations in EPM2A (laforin) or EPM2B (malin) encoding laforin phosphatase and malin ubiquitin E3 ligase, respectively, both involved in glycogen structural integrity. Defective laforin or malin results in neuronal accumulation of malformed insoluble glycogen termed Lafora bodies (LBs).¹ Histologic reports indicate LB accumulation in the inner retinal layers with evidence of bipolar cell atrophy.² Funduscopic retinal examination has been reported unremarkable except in one patient with unilateral optic atrophy that may have been unrelated to LD.^3,4 Recently, retinitis pigmentosa was reported in a 21-year-old patient diagnosed only on skin biopsy, and was highlighted on the journal cover.⁵ A subsequent letter to the editor suggested that this may represent an instance of false-positive interpretation of skin biopsy, but the debate remains unsettled.^1,5,6 We aimed to address this issue by performing multimodal imaging and electrophysiology (e-Methods in links.lww.com/WNL/A580) to characterize the eye phenotype in 4 patients with genetically confirmed LD, concurrently setting the stage to identify potentially useful ophthalmologic biomarkers in LD.