SNRNP200- Associated Retinopathy: In-Depth Clinical Phenotyping and Genetic Characterization

Purpose

To analyze the clinical spectrum and natural history of SNRNP200-associated retinopathy.

Design

Multicenter retrospective, observational cohort study.

Patients

Molecularly confirmed patients with at least 1 disease-causing variant in SNRNP200.

Methods

Clinical data was extracted from the physical and electronic records, including imaging and electrophysiology. Genetic results were reviewed, and the variants assessed.

Main outcome measures

Molecular genetic testing and clinical findings, including best-corrected visual acuity (BCVA), qualitative and quantitative analysis of retinal imaging, and electrophysiology.

Results

Thirty-four patients from 4 countries were identified and assessed longitudinally. The median age was 36.0 years (IQR 27.5-43.5), with a median follow-up of 6.0 years (IQR 2-9.5). Median BCVA was 0.0 LogMAR (IQR 0.0-0.27) at baseline and 0.1 LogMAR (0.0-0.47) at follow-up, with an annual rate of decline of 0.021 LogMAR. The median ellipsoid zone width was 3013.5 µm (IQR 1948.7-3592.2) at baseline and 2400.1 µm (IQR 1136.75-3097.2) at follow-up, with a rate of decline of 21.9 µm/year. Detailed electrophysiology was available for 11 patients, all of whom showed a rod-cone dystrophy with largely preserved macular function in the majority of cases. Genetic analysis identified 21 variants in SNRNP200, including 11 novel variants.

Conclusions

This report represents the largest cohort of patients with SNRNP200-associated retinopathy, with the longest follow-up. Longitudinal analysis shows a preserved central retina until the 6th decade of life. These findings provide critical insights for patient counselling, identifying clinical endpoints, and guiding therapeutic development.