TY - JOUR

T1 - Clinical Characteristics, Mutation Spectrum, and Prevalence of Åland Eye Disease/Incomplete Congenital Stationary Night Blindness in Denmark

AU - Hove, Marianne N

AU - Kilic-Biyik, Kevser Z

AU - Trotter, Alana

AU - Grønskov, Karen

AU - Sander, Birgit

AU - Larsen, Michael

AU - Carroll, Joseph

AU - Bech-Hansen, Torben

AU - Rosenberg, Thomas

PY - 2016/12

Y1 - 2016/12

N2 - 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 low-vision center from 1980 to 2014. A subset of affected males underwent ophthalmologic examinations including psychophysical tests, full-field electroretinography, and spectral-domain 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.

AB - 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 low-vision center from 1980 to 2014. A subset of affected males underwent ophthalmologic examinations including psychophysical tests, full-field electroretinography, and spectral-domain 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.

U2 - 10.1167/iovs.16-19445

DO - 10.1167/iovs.16-19445

M3 - Journal article

C2 - 28002560

VL - 57

SP - 6861

EP - 6869

JO - Investigative Ophthalmology & Visual Science

JF - Investigative Ophthalmology & Visual Science

SN - 0146-0404

IS - 15

ER -