The Online Mendelian Inheritance in Man (OMIM) website lists more than 750 genetic disorders with significant involvement of the retina, choroid, or both. The Retinal Information network online, RetNet, lists nearly 300 different retinal degenerations in which the chromosomal site, and often the specific gene defect, have been identified. Table 13-1 summarizes known retinal dystrophies and their associated genes and loci. Despite their numerous distinctive clinical features, these conditions are characterized by multiple genes that give rise to the same phenotype (genetic heterogeneity) as well as diverse phenotypes that share common causative genes (variable expressivity). Conversely, defects in a particular gene can give rise to different phenotypes; this is referred to as pleiotropy.
The disorders have been divided by 2 anatomic classifications: (1) apparent topography or (2) layer of involvement, such as retina, macula, retinal pigment epithelium (RPE), choroid, and vitreous/retina; however, these distinctions do not always correspond to the sites of the causative gene expression. A second system of organization classifies the disorders based on the inheritance pattern of the disease; however, some genes have variants that can give rise to either autosomal or X-linked dominant or autosomal or X-linked recessive inheritance, respectively. A third approach classifies the disorders by disease phenotype based on clinical examination and electrophysiological and psychophysical testing, but many genes can give rise to overlapping phenotypes.
For convenience, this chapter organizes the retinal and choroidal dystrophies based on clinical phenotypes and anatomic involvement, rather than on molecular genetics. Thus, the reader will note that some genes are causative across multiple phenotypes, and only in rare instances is a specific phenotype defined by a unique causative gene. Disorders with primary diffuse photoreceptor involvement are classified separately from those with predominantly macular involvement, for which the symptoms and prognoses generally differ. The diffuse photoreceptor dystrophy category of disorders is further subcategorized into rod-dominant, cone-dominant, and choroidal syndromes and diseases.
Daiger SP, Sullivan LS, Bowne SJ. Genetic mechanisms of retinal disease. In: Schachat AP, Wilkinson CP, Hinton DR, Sadda SR, Wiedemann P, eds. Ryan’s Retina. Vol 2. 6th ed. Philadelphia: Elsevier/Saunders; 2018:711–721.
OMIM, Online Mendelian Inheritance in Man website. www.omim.org. Accessed March 15, 2018.
RetNet, Retinal Information Network website. https://sph.uth.edu/retnet/. Accessed December 15, 2019.
Table 13-1 Genes and loci associated with inherited retinal dystrophies
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.