Cascade screening for familial hypercholesterolemia from pediatric index cases diagnosed through universal screening

Abstract

Heterozygous familial hypercholesterolemia (HeFH) is an autosomal dominant disorder causing elevated low density lipoprotein cholesterol (LDL-C) and premature atherosclerotic cardiovascular disease. Universal cholesterol screening in childhood leads to children serving as the index case for their family, but efficacy of cascade screening and genetic counseling in this population is not well understood. The institutional pediatric lipid clinic database was queried from 2011 to 2022 for subjects <18 years who met clinical HeFH diagnostic criteria (N = 256). Median peak LDL-C was 198 mg/dL (interquartile range 179–238 mg/dL) and 69.5 % of subjects were the index case. The number of new HeFH cases identified per index case was 3.55 ± 1.87. Genetic counseling was offered to 38.7 % of subjects and genetic testing was completed by 10.9 %, 53.6 % of whom had a pathogenic or likely pathogenic genetic variant for HeFH. Our findings highlight the effectiveness of cascade screening from pediatric index cases identified through universal screening. However, genetic counseling and genetic testing may be underutilized in this population.