A test of automated use of electronic health records to aid in diagnosis of genetic disease

Purpose: Automated use of electronic health records may aid in decreasing the diagnostic delay for rare diseases. The phenotype risk score (PheRS) is a weighted aggregate of syndromically related phenotypes that measures the similarity between an individual's conditions and features of a disease. For some diseases, there are individuals without a diagnosis of that disease who have scores similar to diagnosed patients. These individuals may have that disease but not yet be diagnosed. Methods: We calculated the PheRS for cystic fibrosis (CF) for 965,626 subjects in the Vanderbilt University Medical Center electronic health record. Results: Of the 400 subjects with the highest PheRS for CF, 248 (62%) had been diagnosed with CF. Twenty-six of the remaining participants, those who were alive and had DNA available in the linked DNA biobank, underwent clinical review and sequencing analysis of CFTR and SERPINA1. This uncovered a potential diagnosis for 2 subjects, 1 with CF and 1 with alpha1-antitrypsin deficiency. An additional 7 subjects had pathogenic or likely pathogenic variants, 2 in CFTR and 5 in SERPINA1. Conclusion: These findings may be clinically actionable for the providers caring for these patients. Importantly, this study highlights feasibility and challenges for future implications of this approach. (c) 2023 by American College of Medical Genetics and Genomics. Published by Elsevier Inc.