Klinik und Genetik bei erblichen Netzhautdystrophien

BACKGROUND: Inherited retinal diseases (IRDs) are a clinically and genetically heterogeneous group of usually progressive retinal disorders that frequently lead to severe vision loss. The treatment options for these mostly monogenetic diseases are currently limited. As various treatment innovations are in the phase of clinical development, comprehensive clinical and genetic diagnostics are crucial. OBJECTIVE: This study aimed to characterize a German IRD cohort of 1000 patients, both phenotypically and genetically, to determine clinical characteristics including the genetic clarification rate. Indications for improving care and future treatment can be derived from these. MATERIAL AND METHODS: The medical records of patients reviewed in the IRD clinic at the University Eye Hospital Bonn between 2019 and 2023 were retrospectively reviewed. Demographic data, symptoms, age at symptom onset and diagnosis and genetic findings were collected. Genetic testing included Sanger sequencing, gene panels and exome/genome sequencing. RESULTS: Out of 1000 IRD patients (mean age: 40 years), 822 underwent genetic testing. A causative genetic mutation was identified in 78% of tested individuals. The most frequent clinical diagnoses were retinitis pigmentosa, macular dystrophies (including Stargardt disease). Accordingly, mutations were most frequently detected in the ABCA4, RPGR, USH2A and PRPH2 genes. CONCLUSION: The diagnostic yield of 78% is at the upper end of international IRD studies, which reflects the use of comprehensive sequencing methods. The most frequent IRD genes were consistent with findings from international cohorts. Mutations were detected in over 90 different genes, underlining the genetic heterogeneity of IRDs. Overall, this emphasizes the importance of broad genetic testing, to identify IRD patients for clinical studies and new forms of treatment.