Clinical, Ophthalmic and Genetic Characterization of RPGRIP1-Associated Leber Congenital Amaurosis/Early Onset Severe Retinal Dystrophy.

PURPOSE: To present the clinical characteristics, retinal features, natural history, and genetics of RPGRIP1-Associated Early Onset Severe Retinal Dystrophy (EOSRD)/Leber Congenital Amaurosis (LCA). DESIGN: Retrospective case series. METHODS: Review of clinical notes, multi-modal retinal imaging, and molecular diagnosis of 18 patients (17 families) with EOSRD/LCA and disease-causing variants in RPGRIP1. RESULTS: The mean age of visual symptoms onset was 0.87 ± 1 year (birth-3 years) and the mean age at baseline visit was 11.4 ± 10.2 years (1-39 years). At the baseline visit, 44% of patients were legally blind (range= 2-39 years) and there was no significant association found between age and best corrected visual acuity (BCVA) in cross sectional analysis. Retinal evaluation showed an abolished electroretinogram or a cone-rod dystrophy pattern, none or minimal pigment deposits, a hyperautofluorescent ring at the posterior pole, and a largely preserved central macular architecture, with retained outer nuclear layer and ellipsoid zone island into adulthood. Eleven variants (48%) were previously unreported, and 13 families (76%) had a double null genotype (DN). Twelve patients (67%) had follow up assessments over a 15.7 ± 9.5 year period. The rate of BCVA decline was 0.02 LogMAR (1 letter)/year. CONCLUSIONS: RPGRIP1-EOSRD/LCA often presents at birth or early infancy, with nystagmus, decreased VA, hyperopia, and photophobia. Patients with a DN genotype may develop symptoms earlier and have worse vision. Multimodal imaging may show a hyperautofluorescent posterior pole ring, and relatively preserved central macular architecture, suggesting that the condition is a promising candidate for gene supplementation.

Bilateral vertical gaze palsy due to midbrain infarct associated with iron deficiency anemia in a young boy.

An 8-year-old boy presented with complaints of sudden-onset binocular vertical diplopia of one day duration. Ophthalmic examination showed restricted up- and downgaze movement with rotatory nystagmus. Systemic investigations revealed iron-deficiency anemia and localized acute infarct in the left paramedian rostral and dorsal part of the upper midbrain at the level of the red nucleus on magnetic resonance imaging. The patient was started on oral iron supplement, which resulted in symptomatic as well as clinical improvement after 2 weeks.