Development of a predictive matrix for pre-test genetic counselling in inherited retinal diseases based on data from 1001 patients enrolled in the IRD-PT registry

Genetic testing plays a pivotal role in the management of Inherited Retinal Diseases (IRDs), yet a significant proportion of patients remain without a molecular diagnosis. This study aimed to develop a predictive matrix to estimate the likelihood of diagnostic success in order to manage patient expectations prior to genetic testing. Conducted as a retrospective, single-center cohort study, it analyzed data from 1001 IRD patients across 804 unrelated families enrolled in the IRD-PT registry. Key clinical variables-including age at symptom onset, family history, consanguinity, and referral timing-were evaluated for their association with genetic diagnostic yield. Results showed that 68.03% of families received a solved diagnosis, while 11.19% were likely solved. The presence of consanguinity, a positive family history, or childhood symptom onset significantly increased the probability of a solved diagnosis (up to 81.7%), whereas their absence reduced it to 31.2%. The study culminated in the creation of a conditional probability model that stratifies patients by their likelihood of molecular confirmation. This tool offers clinicians a practical, evidence-based approach to pre-test genetic counselling, enhancing transparency and expectation management for patients undergoing IRD genetic testing.