P2A156: Cascade Screening for Familial Hypercholesterolemia in Pediatrics

Background: Familial hypercholesterolemia (FH) is an autosomal dominant disorder characterized by lifelong high LDL cholesterol (LDL-C), which can cause premature atherosclerotic cardiovascular disease (ASCVD) events if untreated. When children are diagnosed with FH, they can be the first family member to be diagnosed (“index case”). Subsequent screening of potentially affected family members (“cascade screening”) is recommended to identify others with FH, permitting treatment and preventing early ASCVD events. This study determined the effectiveness of cascade screening for FH in a pediatric lipid clinic and examined outcomes of genetic counseling and testing in pediatric patients diagnosed with FH.

Methods: The institutional lipid clinic database was queried for all patients presenting from 2/1/2011-12/31/2022. Children were diagnosed with FH once secondary causes of dyslipidemia were ruled out if LDL-C ≥ 190 mg/dL on two lipid profiles, or LDL-C ≥160 mg/dL on two lipid profiles with personal or family history of high LDL-C or premature ASCVD. Records were reviewed for family history, pharmacotherapy status, and genetic counseling outcomes. Subjects were excluded if family history was not available or incomplete. Data were analyzed using descriptive statistics.

Results: A total of n = 262 subjects met inclusion criteria. Demographic data are in Table 1 . The median peak LDL-C was 199.5 mg/dL (IQR 178.8-238.0 mg/dL), and those managed with statin therapy during the study period included 75.2%. Family history of premature ASCVD was evident in 45.1% of subjects and 68.7% were the index case for their family. The number of new FH cases identified per index case was 3.57 ± 1.91 and the diagnosis of FH was made 17 times post-mortem. Genetic counseling was offered to 38.2% of patients and genetic testing was completed by 9.9%. A pathogenic or likely pathogenic genetic mutation consistent with an FH diagnosis was identified in 5.7% of all subjects.

Conclusion: Cascade screening effectively identifies patients with FH who may otherwise go undiagnosed and represents one effective approach to improve diagnosis rates for FH. This illustrates the need to screen, diagnose, and treat children with FH to reduce the increased risk of ASCVD and premature death in families affected by FH.