Abstract
Background RGS9 (Regulator of G protein Signaling 9) encodes a protein that deactivates G proteins in phototransduction. Pathogenic variants in RGS9 have been described in association with bradyopsia (‘slow vision’), manifesting clinically with delayed adaptation to bright lights and difficulty tracking quickly moving targets. Here we report two unrelated probands harbouring the same homozygous, likely pathogenic missense variant, NM_003835.3: c.895T>C in RGS9.
Methods A retrospective review of the ophthalmic history, clinical examination, pseudo-colour and fundus autofluorescence (FAF) imaging with Optos, Spectralis optical coherence tomography (OCT), and flood-illuminated adaptive optics (AO) imaging and electroretinography (ERG) in accordance with ISCEV standards.
Results A 67-year-old Caucasian female from non-consanguineous parents was referred with childhood-onset poor visual acuity, photophobia and gait disturbance. Best-corrected visual acuity (BCVA) was 6/7.5 OD and 6/15 OS with normal colour vision. Fundus examination, FAF and OCT imaging was normal. ERG demonstrated reduced a-wave in dark-adapted (DA) 10 and flat light-adapted (LA) responses. A 37-year-old male from non-consanguineous parents was referred with difficulty adjusting to dark and light environments, mild photophobia and tinnitus. BCVA was 6/15 OD and 6/9 OS with normal colour vision. Fundus examination, FAF and OCT were normal. ERG at ages 4, 18 and 38 years resembled case 1. Additional ERG testing showed preserved x-wave in DA red response and restoration of a-wave amplitude with increasing inter-stimulus interval from 20 to 50 seconds in DA10. AO imaging demonstrated a preserved foveal cone density.
Conclusions These cases illustrate the importance of performing additional ERG testing beyond the ISCEV standard and cellular imaging in the clinical work up of patients with ERG features that resemble achromatopsia or cone-rod dystrophy.
