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Nathalie Bax, Stanley Lambertus, Cecile van der Poort, B. Jeroen Klevering, Frans P Cremers, Carel C B Hoyng; Clinical and genetic characteristics of intermediate-onset Stargardt disease.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2686.
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To describe the phenotypic and genotypic features in intermediate-onset Stargardt patients. We already described the phenotypes of early- and late-onset Stargardt disease.
Eighty-three Stargardt patients with an age at onset between 11 and 44 years. We reviewed medical records and ophthalmologic examinations for age at onset, best corrected visual acuity (BCVA), ophthalmoscopy, color fundus photography, fundus autofluorescence, fluorescein angiography (FA), spectral-domain optical coherence tomography (SD-OCT), full-field and multifocal electroretinography (ffERG and mfERG), visual field testing and color vision testing. The ABCA4 gene had been analysed for mutations in the protein-coding exons and flanking intronic sequences. A subset of these cases were also analyzed for heterozygous deletions using the MLPA technique.
The mean age at onset was 21.18±8.94 years. Mean duration of follow-up was 17.7±13.9 years. BCVA at last recorded visit was 0.93 logMAR (20/170 Snellen). Irregular yellow-white fundus flecks were present at 91% of the patients at first visit. FA showed a dark choroid in 17 out of 58 patients (29.3%). Forty-nine of 50 patients with SD-OCT images showed (central) retinal pigment epithelium loss. On ffERG at first visit in 48 patients, 44 had normal amplitudes (91.7%). mfERG in 23 patients showed reduced or extinguished central responses. Central visual field loss occurred in 57 out of 68 patients (83.8%). Eight of 51 patients (15.7%) tested for color vision defects had normal color vision. Genetic screening of 143 patients revealed ≥2 ABCA4 mutations in 109 patients, single heterozygous mutations in 29 patients, and no mutations in four patients. The mild variant c.2588G>C was identified in a compound heterozygous manner in 33% of the 143 patients, most frequently in combination with the non-canonical splice variants c.768G>T (n= 13) or c.5461-10T>C (n=7). Based on other studies, both were deemed to be severe variants.
We show that intermediate-onset Stargardt patients also form a distinctive group. Patients have better visual acuity than patients with early-onset Stargardt, but show a more severe phenotype than late-onset Stargardt patients. Visual acuity declines progressively in 5-10 years after age at onset. Yellowish fundus flecks are present in the majority of the patients. This phenotype is often caused by a combination of a mild with a severe ABCA4 mutation.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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