Clinical and Genetic Characteristics of Childhood-onset Stargardt Disease

Abstract

Purpose: Clinical and genetic characterization of 42 patients with childhood-onset Stargardt Disease (STGD).

Methods: Detailed history and ophthalmic examination were undertaken in forty-two patients diagnosed with STGD in childhood, including fundus photography, autofluorescence imaging, spectral-domain optical coherence tomography (SD-OCT), and pattern and full-field electroretinograms. The entire ABCA4 gene was screened by next generation sequencing.

Results: The median ages of onset and the median age at examination were 8.5 years (range 3-16) and 12.0 years (range 7-16), respectively. The median LogMAR visual acuity was 0.74. 26 (59%) of 39 patients with available photographs had macular atrophy with macular/peripheral flecks; eleven (28%) had macular atrophy without flecks; one (2.5%) had numerous flecks without macular atrophy; and one (2.5%) had a normal fundus. Flecks were not identified in 12 patients (31%). SD-OCT detected outer retinal disruption at the fovea in all 21 patients with available images. Electrophysiological assessment demonstrated retinal dysfunction confined to the macula in 9 patients (36%), macular and generalized cone dysfunction in 1 subject (4%), and macular and generalized cone and rod dysfunction in 15 individuals (60%). Two or more disease-associated ABCA4 variants were identified in 34/42 (81%) patients; of these, definitely deleterious variants were present in 22/42 (52%) patients.

Conclusions: Childhood-onset STGD is associated with severe visual loss, early morphological changes, and often generalized retinal dysfunction; despite often less severe fundus abnormalities. The high proportion of deleterious ABCA4 variants supports the hypothesis that the earlier disease onset is, in a large part, due to more severe mutations.

Keywords: 696 retinal degenerations: hereditary • 539 genetics • 509 electroretinography: clinical