Congenital stationary night blindness with a fundus albipunctatus-like yellow-dotted retina associated with compound heterozygous RPE65 variants: A case report

This case describes congenital stationary night blindness (CSNB) with a fundus albipunctatus-like phenotype linked to compound heterozygous RPE65 variants, highlighting the diagnostic value of multimodal imaging and evidence-based variant interpretation.

A retrospective case review including best-corrected visual acuity (BCVA), color vision testing, fundus photography, spectral-domain optical coherence tomography (SD-OCT), full-field electroretinography (ERG), and next-generation sequencing with parental segregation analysis. Variant pathogenicity was assessed using in-silico prediction models (PolyPhen-2 HumDiv and HumVar), and findings were integrated with clinical and imaging data.

A sixteen-year-old male reported lifelong nyctalopia and stable difficulty seeing in dim.

BCVA was 20/30 OD and 20/25 OS with normal color vision. Fundus examination revealed multiple white-yellow flecks along the arcades and mid-periphery with macular sparing. SD-OCT demonstrated preserved outer retinal architecture and an intact ellipsoid zone, and full-field ERG showed preserved rod and cone responses. Genetic testing identified two RPE65 missense variants: c.433G>A (p.Ala145Thr), likely pathogenic, and c.946A>G (p.Asn316Asp), reported as a VUS. PolyPhen-2 analysis classified p.Asn316Asp as damaging (HumDiv/HumVar score 1.000), and parental segregation demonstrated the variants in trans. Integration of genotype and phenotype supports p.Asn316Asp as likely pathogenic.

Compound heterozygosity for hypomorphic RPE65 variants can produce a stationary fundus albipunctatus-like phenotype rather than progressive retinal degeneration. Careful integration of multimodal phenotyping and variant interpretation was essential for confirming disease causality.