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

Šikonja, Jaka (author), Intihar, Urška (author), Jug, Borut (author), Salobir, Neža (author), Trebušak Podkrajšek, Katarina (author), Cevc, Matija (author), Đorđević, Nina (author), Kafol, Jan (author), Gorjanc, Tevž (author), Mlinarič, Matej (author), Čugalj Kern, Barbara (author), Kovač, Jernej (author), Battelino, Tadej (author), Fras, Zlatko (author), Grošelj, Urh (author)

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: Out of 442 children and 299 adults with a definite or probable FH based on clinical criteria, 39 (13.0%) adults and 197 (44.6%) children had also a genetic HeFH. FH causative variants were present in low-density lipoprotein receptor (LDLR) in 159 (67.4%) patients and in apolipoprotein B (APOB) 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.

• Language: English
• Keywords: familial hypercholesterolemia, adults, children, genetics, universal screening, opportunistic screening
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2026
• Number of pages: 7 str.
• Numbering: Vol. 65, art. 100567
• PID: 20.500.12556/RUL-183397
• UDC: 616.1:575
• ISSN on article: 2667-0895
• DOI: 10.1016/j.athplu.2026.100567
• COBISS.SI-ID: 278015491
• Publication date in RUL: 12.06.2026

Record is a part of a journal

• Title: Atherosclerosis plus
• Publisher: Elsevier
• ISSN: 2667-0895
• COBISS.SI-ID: 103569411

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