Clearing the AIR: A PRPH2 mutation identified in the evaluation of presumed autoimmune retinopathy

To detail the identification of a likely pathogenic variant in PRPH2 in a daughter-father duo, highlighting the diagnostic challenges in differentiating nonparaneoplastic autoimmune retinopathy (npAIR) from inherited retinal degeneration (IRD), particularly in the presence of an underlying autoimmune disease.

A 49-year-old woman with a history of systemic autoimmune disease presented with progressive peripheral vision loss, retinal vasculitis, and macular vitelliform lesions. The initial diagnosis of npAIR was later revised to an inherited retinal degeneration when her father was also found to be heterozygous for the same missense, likely pathogenic variant in the PRPH2 gene (c.659G > C:p.R220P). This PRPH2-associated retinopathy was associated with photoreceptor and retinal pigmented epithelium degeneration as well as vascular leakage and retinal edema that resolved with intravitreal steroids.

The case of the proband underscores the diagnostic dilemma of differentiating npAIR from an IRD, especially in the presence of preexisting autoimmune disease. The identification of a likely pathogenic variant in PRPH2 adds to the genetic understanding of the spectrum of phenotypes that can be associated with this IRD. The effectiveness of intravitreal steroids in treating retinal edema in the proband supports its utility in recalcitrant cases of IRD-associated CME or retinal edema.