Age-related macular degeneration with discordant late stage phenotypes in monozygotic twins

Abstract

Purpose: Age-related macular degeneration (AMD) is a complex disease caused by genetic and environmental factors. Monozygotic twins with late stage AMD provide an opportunity to evaluate the role of environmental factors on a genetically uniform background.

Methods: Monozygosity was determined in four twin pairs by genotyping 15 highly polymorphic tetranucleotide repeat markers. Clinically, the monozygotic twin pairs were evaluated by ophthalmologic examination, fundus autofluorescence (FAF) imaging, and, upon suspicion of choroidal neovascular membranes, by fluorescein angiography. Twin pairs were followed over a period of 4-8 years.

Results: Genetically confirmed monozygotic twins with early stages of AMD reveal striking symmetry of early macular pathology. Upon progression to late stage AMD each twin pair developed a discordant phenotype with respect to disease onset and specific phenotype as choroidal neovascularization (CNV) and geographic atrophy (GA).

Conclusions: Genetic risk variants are known to predispose to the development of AMD. Course and visual outcome of the disease, however, appear to be influenced by environmental factors rather than genetic determinants.