Genetic Testing Results in a Preventative Cardiology and Inherited Lipid Disorders Clinic

Abstract

Background/Synopsis

Genetic testing for inherited lipid disorders can facilitate diagnosis, treatment, and family cascade screening. Of the known monogenic dyslipidemias, familial hypercholesteremia (FH) is the most common. FH is caused by inherited pathogenic variants in LDLR, APOB, PCSK9, and LDLRAP1 and is characterized by significantly elevated LDL cholesterol and increased risk for coronary artery disease (CAD). There are limitations to genetic testing and potential insurance implications, thus a shared decision model including a physician and genetic counselor provides optimal decision-making for the patient.

Objective/Purpose

Describe real-world experience of genetic testing at a lipid clinic with involvement of a genetic counselor.

Methods

Electronic health record (EHR) data from October 2021 to December 2023 was reviewed for all patients referred to the Inherited Lipid Disorders Clinic at the University of Pennsylvania for genetic counseling and testing.

Results

A total of 350 patients were referred for genetic testing. Approximately 72% (n=253) were for FH, 13% for other dyslipidemia, 5% for high triglycerides/chylomicronemia syndrome, 3% for partial lipodystrophy, and 5% for cascade screening following positive genetic testing in a family member. Following communication with the genetic counselor, genetic testing orders were placed for 310 patients who agreed to testing, of which 77% (n=239) completed testing. Results for these patients revealed 51 pathogenic variants, 27 positive (but not diagnostic) variants, 72 variants of uncertain significance (VUS), and 128 negative results. Among the 178 FH patients who completed testing, 17% of these patients had genetic testing confirm the diagnosis of FH with pathogenic variants in LDLR, APOB, PCSK9, or LDLRAP1, while 10% of patients were found to have a VUS in one of these 4 genes. Among the 19 hypertriglyceridemia patients, 9 completed testing and 1 pathogenic variant in LPL was detected. Of the 10 patients with partial lipodystrophy, 7 completed testing and 1 pathogenic variant in LMNA was detected. Meanwhile, of the 17 patients referred for cascade screening, 14 completed testing which showed a pathogenic LDLR variant in 8 patients and 1 patient with an LMNA variant. The genetic counselor informed all patients of results.

Conclusions

A high proportion of patients (68%) referred to the lipid clinic for genetic testing completed testing with at-home kits. The majority of patients referred for testing were those with suspected FH. Incorporation of a genetic counselor in the program provides patients with a comprehensive education on the risks and benefits of genetic testing.