Abstract
Background: Genomic testing has transformed rare genetic disease diagnosis, but follow-up studies have not been performed to investigate the longer term impact on patient management, family decision making, and service provision. Methods and results: We collected data in a cohort of 80 infants with suspected monogenic disorders who underwent whole exome sequencing (WES). The median duration of follow-up was 473 days (interquartile range 411–650). Uninformative WES results contributed to the diagnosis of non-Mendelian conditions in seven infants. Undiagnosed infants with an ongoing suspicion of Mendelian disorder (N = 29) received standard-of-care investigations at a cost of AUD$15,585 without any additional diagnoses, while WES data reanalysis at a cost of AUD$11,350 yielded four additional diagnoses. Seventeen patients had changes in management following WES result, with five leading to changes in clinical outcomes. WES diagnosis was not associated with increased tertiary hospital use. The parents of 14 diagnosed children and two undiagnosed children accessed reproductive genetic services at a cost of AUD$39,517. All couples at high recurrence risk and achieving a pregnancy utilized either pre-implantation or prenatal genetic diagnosis. One termination of pregnancy occurred in the undiagnosed group, based on uncertainty regarding recurrence risk. Overall, parents of diagnosed children had eight more pregnancies compared to those without a diagnosis. Conclusions: These data provide further support for the early use of genomic testing in the diagnostic trajectory, highlighting the value of storage and re-analysis of genomic data, benefits in improved patient management without a major increase in healthcare costs, and restoration of parental reproductive confidence.