[Stargardt disease (ABCA4-asssociated retinopathy): Overview of clinical aspects, classification and differential...

Morbus Stargardt (STGD1) is the most common autosomal recessive macular dystrophy and is caused by biallelic variants in the ABCA4 gene located on chromosome 1. More than 1200 disease-associated variants have been described, causing a broad phenotypic spectrum. The hallmark feature is a bilateral, typically slowly progressive visual impairment, although best-corrected visual acuity can be preserved for a long time in patients with foveal sparing. The disease is characterized by lipofuscin accumulation in the retinal pigment epithelium, manifesting as fundus flavimaculatus on funduscopic examination, outer retinal atrophy on optical coherence tomography (OCT) and a characteristic pattern on fundus autofluorescence imaging. While earlier classifications were primarily based on clinical and electrophysiological criteria, current approaches increasingly focus on genotype-phenotype correlations, which can also enable prognostic statements. Severe, early-onset disease courses are predominantly associated with loss of function variants, whereas certain genotypes have been linked to milder and later-onset manifestations. The differential diagnosis remains challenging due to considerable phenotypic overlap with other autosomal-dominant and autosomal-recessive macular dystrophies. Moreover, particularly in late-onset cases, differentiation from geographic atrophy secondary to age-related macular degeneration can be necessary.