Abstract
Purpose :
Inherited Retinal Dystrophies (IRDs) are heterogenous degenerative diseases of the retina with over 300 identified pathogenic genes with diverse expression patterns, developmental and functional roles, and complex phenotypes even within a family. The Penn State IRD clinic was established in 2016 to serve patients with IRDs in Central Pennsylvania. This study aims to map the frequency distribution of IRD-causative genes within the Central PA patient population.
Methods :
This was a retrospective consecutive case series. Medical records of non-blood related patients visiting Penn State’s IRD clinic from 06/14/2016 to 04/28/2023 were reviewed. Demographic, clinical, and genetic data were extracted, and gene frequencies were calculated.
Results :
From 533 patients seen at the Penn State IRD clinic, 315 (59.1%) were female. The average age was 51.4 (range 2 to 92) and 31 (5.8%) were below 18. Over two-thirds (n=360, 67.5%) were referred for retinal evaluation suspecting IRD, other reasons being Plaquenil toxicity (n=80, 15%), neuro-ophthalmologic disease (n=42, 7.9%), and other non-specific disease (n=53, 9.9%). Over half (n=201, 55.8%) evaluated received a provisional IRD diagnosis, of which 113 (56.2%) underwent genetic counseling and testing, most commonly (n=79, 79.3%) through Blueprint Genetics’ 268 IRD gene panel. Of 50 unique IRD-causative genes from 86 patients, over half (n=27, 54%) were linked to retinitis pigmentosa. The gene with the highest frequency was ABCA4 (n=16, 18.6%), followed by BBS1 (n=8, 9.3%), USH2A (n=6, 7%) and CHM (n=6, 7%), confirming prior gene distribution analyses, except for BBS1. Barder-Biedl Syndrome (BBS) -causing BBS1 variants represented >9% of genotypically diagnosed IRDs and 4% of provisional IRD diagnoses, higher than reports in other regions (1-4% and <0.1%, respectively).
Conclusions :
Penn State's IRD clinic has evaluated >500 patients, facilitating gene testing for >50% of suspected IRDs and definitive diagnosis for >75%, exceeding prior diagnostic success rates of 50-60%. The high BBS1 frequency is particularly relevant, as patients require extensive medical surveillance by regional physicians and appropriate care for developmental delay and other features of BBS. This study also highlights the role of region-specific genetic diagnoses in optimizing care. Collaboration with geneticists and public health officials is required to validate and disseminate this data.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.