Abstract
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.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: August 01, 2022
Accepted:
June 24,
2022
Received in revised form:
June 24,
2022
Received:
April 6,
2022
Identification
Copyright
© 2022 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.
