-related retinal disease presenting as isolated cone dysfunction.

PURPOSE

Bialleic pathogenic variants are typically associated with severe Leber congenital amaurosis (non-recordable electroretinography [ERG]) and less commonly with cone-rod dystrophy. This report highlights isolated cone dysfunction as an alternative -related presenting phenotype.

METHODS

Retrospective case series.

RESULTS

Four individuals (two sibships from two unrelated families) had low vision, nystagmus, photophobia, and a grossly normal retinal appearance since soon after birth. ERG confirmed non-recordable photopic function with normal scotopic function. Genetic testing revealed affected members from the two families to harbor two different homozygous variants (Family 1: c.3565C>T; p.Arg1189*; Family 2: c.2711_2741delinsATATTAG; p.Gly904_Lys914delinsAspIIeArg). Follow-up for Family 1 revealed deterioration of pan-retinal function (non-recordable ERGs by 11 and 7 years old) and thus a final diagnosis of cone-rod dystrophy. Follow-up for Family 2 showed stable retinal function (normal ERG scotopic tracings maintained at 12 and 21 years old) and thus a diagnosis of isolated cone dysfunction.

CONCLUSIONS

Isolated cone dysfunction that progresses to pan-retinal dysfunction or remains relatively stationary is an alternative phenotype related to biallelic pathogenic variants.