Universal screening for familial hypercholesterolemia in 2 populations

Purpose: In Europe, >2 million individuals with familial hypercholesterolemia (FH) are currently undiagnosed. Effective screening strategies for FH diagnosis in childhood are urgently needed. We assessed the overall performances of 2 different FH screening programs in children: universal screening program with opt-out and opt-in type participation. Methods: We analyzed the data from 2 independent populations based on >166,000 individuals screened for hypercholesterolemia. Genetic analyses of FH-related genes were finalized in 945 children and 99 parents. Results: A total of 305 (32.3%) children were genotyped as positive or with a variant of uncertain significance in FH-related genes. For low-density lipoprotein cholesterol levels of 3.5 mmol L (135.3 mg/dL), the overall sensitivity and specificity for confirming FH were 90.5% and 55.3%, respectively. As part of child-parent screening, in >90% of the families, the parent with reported higher cholesterol levels was positive for the familial genetic variant. The cohort-based prevalence of FH from the opt-out universal screening program was estimated to be 1 in 431 individuals (95% CI = 1/391-1/472). Conclusion: Universal 3-step FH screening approach in children enabled detection of most children and their parents in every generation screened at reasonable costs. Opt-out screening strategy might be preferable over opt-in screening strategy. (C) 2022 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.

Automated summary

This study assessed the performance of two different screening programs for diagnosing familial hypercholesterolemia (FH) in children and found that the opt-out screening strategy was more advantageous than the opt-in strategy, as it could effectively detect FH patients and their family members.