Clinical and genetic characteristics of late-onset Stargardt's disease

To describe the genotype and phenotype of patients with a late-onset Stargardt's disease (STGD1).

Retrospective case series.

Twenty-one unrelated STGD1 patients with an age at onset of ≥45 years and ≥1 rare variant in the ABCA4 gene.

Ophthalmologic examination, including best-corrected visual acuity (VA), Amsler grid testing, fundus photography, fluorescein angiography (FA), spectral-domain optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging, full-field electroretinography (ERG), multifocal ERG, and central visual field testing. Analysis of the ABCA4 gene was performed using microarray analysis, sequencing, and multiplex ligation-dependent probe amplification. In addition, the PRPH2 and CFH genes were sequenced.

Age at onset, VA, fundus appearance, FA, FAF, and OCT findings; ABCA4 mutations; and genotype-phenotype correlation.

The mean age at onset was 55 years (range, 45-72 years). Seven patients were diagnosed without visual symptoms (age range, 45-83 years). The VA was ≥20/40 in 24 eyes of 14 patients (59%) owing to foveal sparing. On ophthalmoscopy, late-onset STGD1 showed flavimaculatus flecks (15 patients), small flecks surrounding mottled foveal changes (3 patients), extensive chorioretinal atrophy (2 patients), or small yellowish spots in the macula (1 patient). The fundus flecks showed increased autofluorescence on FAF. The choroidal background fluorescence on FA was obscured in 16 patients (80%). We found a single heterozygous ABCA4 variant in 11 patients (52%), 2 compound heterozygous variants in 8 patients (38%), and a homozygous variant in 2 patients (10%). No PRPH2 or CFH mutations were detected.

Late-onset STGD1 is at the mild end of the spectrum of retinal dystrophies caused by ABCA4 mutations. The VA is frequently preserved in late-onset STGD1 patients owing to foveal sparing. This phenotype may be caused by 1 or 2 ABCA4 variants. The differential diagnosis between late-onset STGD1 and age-related macular degeneration may be challenging. A thorough clinical and genetic analysis makes a distinction possible, which is important for clinical and genetic counseling.

The authors have no proprietary or commercial interest in any of the materials discussed in this article.