Familial Hypercholesterolemia (FH) Panel

This test is used to detect point mutations, deletions, and duplications in the LDLR, APOB, and PCSK9 genes. Variants in these (and other) genes have been associated with familial hypercholesterolemia (FH). 

This test may be appropriate to confirm a diagnosis of familial hypercholesterolemia (FH) for

• Individuals with a personal history of hypercholesterolemia or an uncertain clinical diagnosis of FH
  • Clinical diagnostic criteria are available through the Dutch Lipid Clinic Network,¹ the Simon Broome Register Group,²  the US MEDPED Program,³ and the National Lipid Association⁴
• Individuals with a personal or family history of developing cardiovascular disease or coronary artery disease at a young age
• Individuals with a personal or family history of visible lipid deposits in the tendons (tendon xanthoma) or eyes (corneal arcus)
• Children and adolescents with a clinical presentation consistent with FH⁵
• Adults with severe hypercholesterolemia with elevated levels of LDL cholesterol (LDL-C) ≥190mg/DL (4.9 mmol/L) without an identified secondary cause⁵

When multiple family members are affected, the person with the earliest symptom onset should be tested first if possible.

Informed consent is strongly recommended before genetic testing.

If the patient has a known familial variant(s) in the LDLR, APOB, or PCSK9 genes, the Familial Hypercholesterolemia (FH), Single Site test (test code 94878) may be ordered. Official test result(s) from the family member(s) must be submitted for laboratory review. For more information, please call Quest Genomics Client Services at 1.866.GENE.INFO (1.866.436.3463) to speak with a genetic counselor.

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

Testing is indicated when a diagnosis of familial hypercholesterolemia (FH) is suspected or a clinical diagnosis of FH needs to be confirmed. Consider testing patients if they have a personal or family history that meets clinical diagnostic criteria or leads to an uncertain diagnosis.

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 and/or earlier onset than 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 a pathogenic or likely pathogenic variant was not found in the LDLR, APOB, or PCSK9 genes. Implications of this result depend on the patient’s personal medical history and family history:

• Patient with elevated LDL cholesterol levels: The patient should continue to be managed based on current guidelines. A negative result does not eliminate the possibility of familial hypercholesterolemia (FH), as other known or unknown genes may cause this phenotype. In some situations, additional genetic testing may be appropriate. 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, yet with family history suspicious for FH: Testing an affected family member is recommended for proper risk assessment. In some situations, additional genetic testing may be appropriate. Please call Quest Genomics Client Services at 1.866.GENE.INFO (1.866.436.3463) to discuss possible additional testing with a genetic counselor.

A variant of unknown significance (VUS) result means that the variant has not been previously described in the literature or the clinical significance is unclear based upon currently available evidence. Medical management decisions should be based on personal and family history.

The classification and interpretation of the variant(s) identified reflect the current state of Quest’s understanding at the time of the report. Variant classification and interpretation are subject to professional judgment and may change for a variety of reasons including, but not limited to, updates in classification guidelines and availability of additional scientific and clinical information. It is important to check in with the laboratory annually for variant updates because new information regarding the variant and classification may become available over time.

Please visit www.questdiagnostics.com/VariantIQ for information about variant classification. For more information, please call Quest Genomics Client Services at 1.866.GENE.INFO (1.866.436.3463) to speak with a genetic counselor.