Natural History of Autosomal Recessive IMPG2-Associated Retinal Dystrophy

Abstract

Purpose: To describe the natural history of autosomal recessive IMPG2-associated retinal dystrophy.

Design: Multicenter international retrospective case series.

Methods: Review of clinical notes, retinal imaging including fundus autofluorescence (FAF) and optical coherence tomography (OCT), and molecular genetic testing, of sixty patients with molecularly confirmed IMPG2-associated retinal dystrophy from 14 tertiary eye centers. Qualitative OCT and FAF imaging analysis.

Results: In total, 60 patients from 52 pedigrees with likely disease-causing variants in IMPG2 from 14 tertiary referral centers in 11 countries were ascertained for phenotyping. Twenty-two patients were females (36.7%). Of those with documented age of disease onset, 23% had "late onset" (>18 years old [yo]) with a mean age of onset of 34.3 yo, and 77% had "early onset" disease (<18 yo) with a mean age of onset of 10.8 yo. Mean best-corrected visual acuity (BCVA) was 0.55 LogMAR at a mean age of 33 yo. Forty-eight percent of the patients presented with nyctalopia and 38% presented with decreased BCVA. Eighty-eight percent of the patients were myopic. Foveal involvement with atrophic changes was a common finding on OCT and FAF. Fifty-three variants were identified: 13 missense (25%), 12 nonsense (23%), 11 splicing variants (21%), 16 frameshifts (30%), and one large deletion (2%). Twenty-one (40%) of the variants were not previously clinically characterized.

Conclusion: Autosomal recessive IMPG2-retinal dystrophy is typically an early onset retinal dystrophy associated with poor visual acuity. Younger patients are more likely to benefit from intervention in future trials due to early macular involvement in most patients.