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Clinical, Ophthalmic, and Genetic Characterization of RPGRIP1-Associated Leber Congenital Amaurosis/Early-Onset
Malena Daich Varela1, Mrunmayi Jeste2, Thales A C de Guimaraes1
1Moorfields Eye Hospital (M.D.V., T.A.C.deG., O.A.M., G.A., A.R.W., M.M.), London, United Kingdom; UCL Institute of Ophthalmology, University College London (M.D.V., T.A.C.deG., O.A.M., G.A., A.R.W., M.M.), London, United Kingdom.
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, multimodal 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 to 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, no 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 (DN) genotype. Twelve patients (67%) had follow-up assessments over a 15.7 ± 9.5-year period. The rate of BCVA decline was 0.02 logarithm of the minimum angle of resolution (1 letter)/year.
Conclusions:
RPGRIP1 EOSRD/LCA often presents at birth or early infancy, with nystagmus, decreased visual acuity, 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.
