Clinical characteristics, mutation spectrum, and prevalence of Åland eye disease/incomplete congenital stationary night blindness in Denmark

Abstract

PURPOSE. To assess clinical characteristics, foveal structure, mutation spectrum, and prevalence rate of Åland eye disease (AED)/incomplete congenital stationary night blindness (iCSNB). METHODS. A retrospective survey included individuals diagnosed with AED at a national lowvision center from 1980 to 2014. A subset of affected males underwent ophthalmologic examinations including psychophysical tests, full-field electroretinography, and spectraldomain optical coherence tomography. RESULTS. Over the 34-year period, 74 individuals from 35 families were diagnosed with AED. Sixty individuals from 29 families participated in a follow-up study of whom 59 harbored a CACNA1F mutation and 1 harbored a CABP4 mutation. Among the subjects with a CACNA1F mutation, subnormal visual acuity was present in all, nystagmus was present in 63%, and foveal hypoplasia was observed in 25/43 subjects. Foveal pit volume was significantly reduced as compared to normal (P < 0.0001). Additionally, outer segment length at the fovea was measured in 46 subjects and found to be significantly reduced as compared to normal (P < 0.001). Twenty-nine CACNA1F variations were detected among 34 families in the total cohort, and a novel CABP4 variation was identified in one family. The estimated mean birth prevalence rate was 1 per 22,000 live-born males. CONCLUSIONS. Our data support the viewpoint that AED, iCSNB, and X-linked cone-rod dystrophy 3 are designations that refer to a broad, continuous spectrum of clinical appearances caused in the majority by a variety of mutations in CACNA1F. We argue that the original designation AED should be used for this entity.