Familial Hypercholesterolemia (FH) Single Site

This test is used to determine whether a patient has a certain variant at a single site within the LDLR, APOB, or PCSK9 genes. Variants in the LDLR, APOB, and PCSK9 genes have been associated with familial hypercholesterolemia (FH). A genetic test report from a family member(s) with a previously identified variant(s) is required to perform this test. The test is capable of detecting point mutations as well as deletions/duplications, based on family member test results.

This test may be appropriate for patients with a family history of a known variant(s) in the LDLR, APOB, or PCSK9 genes. Variants in these (and other) genes have been associated with familial hypercholesterolemia (FH). Official test results from the family member must be submitted for laboratory review. For more information or to discuss the family history with a Quest Diagnostics genetic counselor, please call Quest Genomics Client Services at 1.866.GENE.INFO (1.866.436.3463).

Informed consent is strongly recommended before genetic testing.

When FH is suspected and no previous LDLR, APOB, or PCSK9 genetic test result from a family member is available, the Familial Hypercholesterolemia (FH) Panel (test code 94877) is the appropriate test to order.

The Familial Hypercholesterolemia (FH) Panel is appropriate for individuals with a personal history of hypercholesterolemia based on the Simon Broome criteria,¹ Dutch Lipid Clinic Network criteria,² US MedPed Program criteria,³ or the National Lipid Association criteria⁴; a personal or family history of cardiovascular disease or coronary artery disease at a young age; or a personal or family history of visible lipid deposits in the tendons (tendon xanthomas) or eyes (corneal arcus). 

Please call Quest Genomics Client Services at 1.866.GENE.INFO (1.866.436.3463) to discuss a specific case with a genetic counselor.

A positive result means that at least 1 pathogenic or likely pathogenic variant has been detected.  The presence of a single pathogenic variant is considered sufficient to cause familial hypercholesterolemia (FH). Individuals with FH are at risk of developing high levels of LDL cholesterol (LDL-C), which may increase the risk for premature coronary artery disease and myocardial infarction. Patients with FH may also develop visible lipid deposits in the tendons (tendon xanthoma) or eyes (corneal arcus). Those with FH may have either heterozygous FH (HeFH), the presence of a single pathogenic variant, or homozygous FH (HoFH), the presence of 2 pathogenic variants. Patients with HoFH tend to have more severe symptoms or earlier onset as compared to those with HeFH.

The FH Foundation provides information and resources about FH (https://familyheart.org/familial-hypercholesterolemia). In addition, clinical management guidelines are available from the National Lipid Association (https://www.lipid.org) and the European Atherosclerosis Society (https://www.eas-society.org). The 2026 Guideline on the Management of Dyslipidemia provides management guidelines.⁵ Consider referring the patient to a center experienced in treating patients with FH. Counselors at these centers can discuss treatment options with the patient. Genetic counseling for family members is advised. 

A negative result means that the familial variant was not found. Implications of this result depend on the patient’s personal medical history and family history:

• Patient with elevated cholesterol (LDL-C levels). The patient should continue to be managed based on current guidelines. In certain instances, it may be appropriate to test for other variants in the LDLR, APOB, or PCSK9 genes. Please call Quest Genomics Client Services at 1.866.GENE.INFO (1.866.436.3463) to discuss possible additional testing with a genetic counselor.
• Patient without elevated LDL-C levels. The patient is not at increased risk for hypercholesterolemia based on the result. The risk for hypercholesterolemia is based on his or her personal history.