Heterozygous Familial Hypercholesterolemia (HeFH) is an autosomal dominant genetic disorder that affects approximately 1 in 300 people1,2 worldwide, making it the most common life-threatening inherited metabolic condition. It is characterized by lifelong abnormally high levels of low-density lipoprotein cholesterol (LDL-C) that cause atherosclerotic cardiovascular disease (ASCVD) and premature cardiovascular disease events, including myocardial infarction and stroke.3 Without treatment, patients with HeFH often develop ASCVD events before age 60.4 When treatment is started in childhood, most of the excess cardiovascular risk is ameliorated.5 For these reasons, universal cholesterol screening in childhood is recommended by the National Heart, Lung, and Blood Institute and the American Academy of Pediatrics, with identification of HeFH as a primary goal.6 When children are diagnosed with HeFH, they can serve as the index case for cascade screening of potentially affected relatives. This allows for identification of additional people with HeFH and provides the opportunity to begin lipid lowering treatment and prevent early cardiovascular events. Previous studies, primarily in adults, have demonstrated cascade screening identifies 0.92 to 2.1 new cases of HeFH per index case.3, 7, 8, 9

In addition to universal cholesterol screening, genetic counseling and testing may be offered to patients with HeFH to definitively confirm their diagnosis. Genetic testing has been recommended for patients in the United States (U.S.) with definite or probable HeFH since 2018,10 as lipid-modifying therapy that targets specific HeFH variants become increasingly available. Additionally, a genetic diagnosis of HeFH is associated with higher rates of statin use in pediatrics.11 However, a U.S.-based registry study reported only 1.6 % of pediatric FH patients had a confirmed pathogenic variant on genetic testing.12

The purpose of this study was to determine the current real-world effectiveness of cascade screening in a pediatric lipid clinic and examine the outcomes of genetic counseling and testing in pediatric patients with HeFH.