The study of previously published ABCA4 variants led to the conclusion that up to a quarter of ABCA4-associated disease displays complex genetic architecture, where together with two ABCA4 alleles, additional genetic or non-genetic factors play a significant role in the development of late-onset ABCA4-associated STGD1[34]. This evidence concerns the gene ABCA4 and severe early-childhood-onset retinal dystrophy.