Parallel screening strategies reveal distinct phenotypic and genotypic profiles of familial hypercholesterolemia in children and adults

Background: Multiple familial hypercholesterolemia (FH) screening strategies are recommended, but how they work together within a population remains poorly understood. Here, we aimed to compare the characteristics of children diagnosed through a universal screening program with those of adults identified through opportunistic screening. Methods: In this retrospective cross-sectional study, we analyzed the clinical and genetic characteristics of children and adults with genetically confirmed heterozygous FH (HeFH). Results: ) in 77 (32.6%) patients. The combined screening approach identified 44 disease-causing variants, of which 2 and 25 were unique to the adult and pediatric cohort, respectively. The proportion of children with missense variants was significantly higher (172 [87.3%] vs. 27 [69.2%]; p = 0.005), whereas the proportion of termination variants was significantly lower (20 [10.2%] vs. 11 [28.2%]; p = 0.002) compared to the adult group. Adults had higher adjusted low-density lipoprotein cholesterol compared to children. Conclusions: Our study suggests that opportunistic adult screening identifies more severe FH phenotypes, while universal pediatric screening detects milder cases.