Characterisation and prevalence of inherited retinal diseases in the Finnish population reveals enrichment of population-specific phenotypes and causative variants

Abstract

Aims: This study aims to assess clinical and genetic characteristics as well as the prevalence of inherited retinal dystrophies (IRD) and their subphenotypes in the Finnish founder population.

Methods: A retrospective analysis of clinical and genetic data from Northern Finnish patients diagnosed with IRD between 1996 and 2023 at Oulu University Hospital, Finland, was conducted.

Results: The cohort comprised 582 patients with IRD, categorised into 16 different subphenotypes. Pathogenic or likely pathogenic variants explaining IRD were identified in 36% (n=210/582) of all patients and 80% (n=210/261) of genetically tested patients with IRD. Diagnostic yields varied between different IRD subphenotypes. The genetic aetiology was most commonly confirmed in X-linked retinoschisis, severe early childhood-onset retinal dystrophy, congenital stationary night blindness and choroideremia. The lowest rates of causative variant identification were observed in cone or cone-rod dystrophy and macular dystrophy. In total, 70 pathogenic or likely pathogenic variants were identified across 39 different genes; variants in the FZD4 and RPGR genes were the most prevalent. Over half of the variants were enriched in the Finnish population. The estimated total prevalence of IRDs in Northern Finland was 69.8/100 000 (1:1432). The prevalence of the most common subphenotypes was as follows: retinitis pigmentosa, 25.3/100 000; X-linked retinoschisis, 10.7/100 000; Usher syndrome, 8.9/100 000; choroideremia, 7/100 000 and cone or cone-rod dystrophy, 6/100 000.

Conclusion: The Northern Finnish population exhibits an enrichment of population-specific IRD-associated variants, resulting in a high overall prevalence of IRDs and an increased prevalence of selected retinal subphenotypes, such as retinoschisis, choroideremia and Usher syndrome types 3 and 1.

Keywords: Diagnostic tests/Investigation; Dystrophy; Epidemiology; Genetics; Retina.

Figure 1. Flowchart of the study population. IRD, inherited retinal dystrophy.

Figure 2. The distribution of genotypes and diagnostic yield in the seven most prevalent phenotypes of Northern Finnish patients with non-syndromic inherited retinal dystrophy. CD, cone dystrophy; CHM, choroideremia; CRD, cone-rod dystrophy; FEVR, familial exudative vitreoretinopathy; LCA, Leber’s congenital amaurosis; MD, macular dystrophy; RP, retinitis pigmentosa; SECORD, severe early childhood-onset retinal dystrophy; XLRS, X-linked retinoschisis.

Figure 3. Clinical and genetic heterogeneity in Finnish patients with IRD. Phenotypes that did not overlap with multiple genes are not presented. CD, cone dystrophy; CRD, cone-rod dystrophy; LCA, Leber’s congenital amaurosis; MD, macular dystrophy; RP, retinitis pigmentosa; SECORD, severe early childhood-onset retinal dystrophy.