Ȧland Island eye disease in two patients harboring novel CACNA1F variants

Ȧland Island eye disease (ȦIED) is a rare X-linked recessive condition caused by mutations in the CACNA1F gene. The ȦIED phenotype involves an overlap of canonical features of ocular albinism and congenital stationary night blindness (CSNB), thereby presenting a diagnostic challenge. Genetic testing often cannot distinguish between ȦIED and CSNB, as many mutations in CACNA1F are known to cause either ȦIED, CSNB, or conditions with ambiguous phenotypes along the ȦIED/CSNB continuum. Therefore, it is necessary to expand the landscape of CACNA1F mutations responsible for this spectrum of conditions. We report two novel CACNA1F variants in patients with a clinical presentation of ȦIED, including low visual acuity, congenital nystagmus, high myopia, hypopigmented fundi, foveal hypoplasia, and choroidal thinning. Electroretinographic findings included decreased rod- and cone-mediated responses, electronegative mixed responses, as well as a novel finding of electronegative rod-mediated responses. While these patients' presentations are consistent with ȦIED, future studies will be needed to determine whether these novel CACNA1F variants are exclusive to ȦIED or can cause phenotypes along the entire ȦIED/CSNB2A spectrum.