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Cascade screening for familial hypercholesterolemia from pediatric index cases diagnosed through universal screening
Morgan Lentz1, Megan Benoy2, Xiao Zhang1
1Department of Pediatrics, Division of Pediatric Cardiology, University of Wisconsin School of Medicine and Public Health. Madison, WI, USA (Ms Lentz, Dr Zhang and Dr Peterson).
Insights
Cascade screening from pediatric index cases effectively identifies new familial hypercholesterolemia (HeFH) cases. However, genetic counseling and testing for HeFH are underutilized in this young population.
Area of Science:
- Genetics
- Cardiology
- Pediatrics
Background:
- Familial hypercholesterolemia (HeFH) is an inherited condition leading to high LDL-C and early heart disease.
- Universal childhood cholesterol screening identifies index cases, but cascade screening effectiveness is unclear.
Purpose of the Study:
- To evaluate the efficacy of cascade screening and genetic counseling in children diagnosed with HeFH.
- To assess the utilization of genetic counseling and testing in pediatric HeFH cases.
Main Methods:
- Retrospective analysis of a pediatric lipid clinic database (2011-2022).
- Inclusion of pediatric subjects (<18 years) meeting clinical HeFH criteria.
- Data collection on LDL-C levels, index case status, and genetic counseling/testing uptake.
Main Results:
- 256 pediatric HeFH subjects identified; 69.5% were index cases.
- Average of 3.55 new HeFH cases identified per index case.
- Genetic counseling offered to 38.7%, testing completed by 10.9%; 53.6% had pathogenic variants.
Conclusions:
- Cascade screening from pediatric index cases is effective for identifying new HeFH diagnoses.
- Genetic counseling and testing for HeFH in pediatric populations appear underutilized.
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.
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