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. 2024 Oct:266:255-263.
doi: 10.1016/j.ajo.2024.05.007. Epub 2024 May 19.

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

Malena Daich Varela  1 , Mrunmayi Jeste  2 , Thales A C de Guimaraes  1 , Omar A Mahroo  3 , Gavin Arno  1 , Andrew R Webster  1 , Michel Michaelides  4
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Free article

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

Malena Daich Varela et al. Am J Ophthalmol. 2024 Oct.
Free article

Abstract

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.

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