Ezimamaka Ajufo1,2, Emil M deGoma1, Anna Raper1, Kristen Dilzell Yu1, Marina Cuchel1, Daniel J Rader3. 1. Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. 2. Department of Internal Medicine, University of Texas Southwestern, Dallas, TX, USA. 3. Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. rader@pennmedicine.upenn.edu.
Abstract
PURPOSE: Family-based cascade screening from index probands is considered an effective way of identifying undiagnosed individuals with familial hypercholesterolemia (FH). The role of genetic testing of the proband in the success of cascade screening for FH is unknown. METHODS: We randomized 240 individuals with a clinical diagnosis of FH to genetic testing for FH (n = 160) or usual care with lipid testing alone (n = 80). The primary study endpoint was the proportion of probands with at least one relative enrolled in the study within one year after the notification of results. RESULTS: Proband median age was 59 (47-67) and 71% were female. Only 28 (12%) probands succeeded in enrolling a relative. While the genetic testing group had a higher proportion of probands with relatives enrolled (13.1%) compared with the usual care group (8.8%), this difference was not significant (p = 0.40). In subgroup analyses, enrollment of a relative was higher in the pathogenic variant group (22.7%) compared to the no pathogenic variant (9.5%) and usual care groups (8.8%) (p = 0.04). CONCLUSION: We observed a low rate of family participation in cascade screening despite repeated recommendations to probands. Compared to usual care, genetic testing did not improve family participation in cascade screening for FH. CLINICAL TRIAL NUMBER: NCT04526457.
PURPOSE: Family-based cascade screening from index probands is considered an effective way of identifying undiagnosed individuals with familial hypercholesterolemia (FH). The role of genetic testing of the proband in the success of cascade screening for FH is unknown. METHODS: We randomized 240 individuals with a clinical diagnosis of FH to genetic testing for FH (n = 160) or usual care with lipid testing alone (n = 80). The primary study endpoint was the proportion of probands with at least one relative enrolled in the study within one year after the notification of results. RESULTS: Proband median age was 59 (47-67) and 71% were female. Only 28 (12%) probands succeeded in enrolling a relative. While the genetic testing group had a higher proportion of probands with relatives enrolled (13.1%) compared with the usual care group (8.8%), this difference was not significant (p = 0.40). In subgroup analyses, enrollment of a relative was higher in the pathogenic variant group (22.7%) compared to the no pathogenic variant (9.5%) and usual care groups (8.8%) (p = 0.04). CONCLUSION: We observed a low rate of family participation in cascade screening despite repeated recommendations to probands. Compared to usual care, genetic testing did not improve family participation in cascade screening for FH. CLINICAL TRIAL NUMBER: NCT04526457.
Authors: Hana Bangash; Ahmed Makkawy; Justin H Gundelach; Alexandra A Miller; Kimberly A Jacobson; Iftikhar J Kullo Journal: JMIR Hum Factors Date: 2022-02-15
Authors: Tara J Schmidlen; Sara L Bristow; Kathryn E Hatchell; Edward D Esplin; Robert L Nussbaum; Eden V Haverfield Journal: Front Genet Date: 2022-06-16 Impact factor: 4.772