Rate of manifesting carriers and other unexpected findings on carrier screening

To ascertain the rate of unexpected findings on carrier screening (CS) and assess whether implications are disclosed to patients.

We performed a retrospective observational study of subjects who had CS after pre-test counseling from a licensed genetic counselor at a large tertiary care center. We quantified the rate of unexpected finding on CS, defined as manifesting carriers (MCs), genotypes predicting phenotype, and chromosome abnormalities. We determined how often patients were informed of implications. We performed subgroup analyses by type of unexpected finding and calculated odds ratios (OR) and 95% confidence intervals (CI) for carrier testing methodology (genotype) and number of genes tested.

A total of 4685 patients had CS over the selected time frame. Of those patients, 412 patients (8.8%) had one unexpected finding and 29 patients (0.6%) had two or more findings. In total, 466 unexpected findings were identified, including 437 MC conditions, 23 genotypes predicting phenotype, and 6 chromosome abnormalities. Patients were informed of the implications for MCs, genotypes predicting phenotype, and chromosome abnormalities in 27.6%, 91.3%, and 100% of cases, respectively. More unexpected findings were detected with sequencing compared to genotyping (OR 2.21 and 95% CI 1.76-2.76) and with ≥200 gene panels compared to <200 gene panels (OR 1.79 and 95% CI 1.47-2.17).

This study highlights that nondisclosure of unexpected findings on CS is common and underscores the need for further research to improve post-test counseling and follow-up.