Background: More than one million individuals in the US are estimated to have Familial Hypercholesterolemia (FH), however fewer than 1% have been diagnosed. Family-based cascade screening from identified probands is widely recommended to improve the identification of FH. However, cascade screening is not effectively performed in the US, and genetic testing for FH is rarely performed in routine clinical care.
Hypothesis: We hypothesized that genetic testing of FH probands and identification of a causative mutation would enhance the success of family based cascade screening
Methods: In this single-site study, patients in an academic health system with LDL-C≥220 mg/dl were randomized to genetic testing for FH (n=160) or lipid testing alone (n=80). Probands were told of positive genetic results. All probands were contacted on at least three separate occasions and encouraged to invite their relatives to participate in cascade screening, with genetic testing offered to relatives of the mutation positive proband and lipid testing only for those who were mutation negative or not genetically tested. The study period lasted for 52 weeks following the initial communication of results to the proband.
Results: Of the 160 probands randomized to genetic testing, 44 (28%) were found to be mutation-positive. Despite poor overall relative participation, the proportion of probands with an enrolled relative was significantly higher in the mutation-positive group (22.7%) compared to the mutation-negative group (9.5%) and the no genetic testing group (8.8%) (p=0.0403). The number of relatives enrolled per proband was also significantly higher in the mutation-positive group (0.38) compared to the mutation-negative group (0.16) and the no-genetic testing group (0.09) (p=0.0076).
Conclusion: Despite repeated contact with probands to encourage family screening, the overall participation of relatives in cascade screening was low. However, we found that a genetic testing for FH with a positive genetic result improved participation in cascade screening.