Comparison of Worldwide Disease Prevalence and Genetic Prevalence of Inherited Retinal Diseases and Variant Interpretation Considerations

Cold Spring Harb Perspect Med. 2024 Feb 1;14(2):a041277. doi: 10.1101/cshperspect.a041277.


One of the considerations in planning the development of novel therapeutic modalities is disease prevalence that is usually defined by studying large national/regional populations. Such studies are rare and might suffer from inaccuracies and challenging clinical characterization in heterogeneous diseases, such as inherited retinal diseases (IRDs). Here we collected reported disease prevalence information on various IRDs in different populations. The most common IRD, retinitis pigmentosa, has an average disease prevalence of ∼1:4500 individuals, Stargardt disease ∼1:17,000, Usher syndrome ∼1:25,000, Leber congenital amaurosis ∼1:42,000, and all IRDs ∼1:3450. We compared these values to genetic prevalence (GP) calculated based on allele frequency of autosomal-recessive IRD mutations. Although most values did correlate, some differences were observed that can be explained by discordant, presumably null mutations that are likely to be either nonpathogenic or hypomorphic. Our analysis highlights the importance of performing additional disease prevalence studies and to couple them with population-dependent allele frequency data.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Leber Congenital Amaurosis* / genetics
  • Mutation
  • Prevalence
  • Retinal Diseases* / epidemiology
  • Retinal Diseases* / genetics
  • Retinitis Pigmentosa* / genetics

Supplementary concepts

  • Amaurosis congenita of Leber, type 1