FH Genetic Test Results

What happens after I receive my FH genetic test results?

Following a genetic test, a certified genetic counselor or knowledgable physician should discuss the results of genetic testing and their implications with you. This discussion should include:

  • how to empower yourself with results of the genetic testing in terms of medical management
  • addressing risks in the family
  • offering lipid screening and/or genetic testing to other relatives (if an FH disease-causing variant is identified)
  • and other issues.

What happens if there is a positive FH genetic test result?

Whether or not someone receives a positive or negative test result, ideally they will undergo genetic counseling and get an explanation of all of their options.

A positive genetic test result means that a disease-causing variant was identified. This result confirms a diagnosis of FH. Because there is a 50% chance that an individual’s parents, siblings, and children have also inherited this variant, genetic testing (for the specific variant detected) can be performed on these individuals to determine who else in the family is at risk. This is known as family screening.Early identification and management can lead to heart disease prevention.

Where available, genetic counselors can be ideal “family navigators” who can help patients address familial risks. To find a genetic counselor in your area, please visit: https://www.nsgc.org/findageneticcounselor

What happens if there is a negative FH genetic test result?

If a person has been clinically diagnosed with FH and receives a negative test result, it does not mean that they do not have FH—it simply means that their genetic cause(s) were not identified with current knowledge and current genetic testing technologies. About 30-40% of people with FH may test negative. These results may be “false negatives” or the person might have a mutation that has not yet been identified to be pathogenic, or disease causing. Someone could also have a variant in a gene that has not been currently identified. A genetic counselor can help you understand what a pathogenic variant or a VUS might mean for you and your family. It is important to continue FH management with the appropriate treatment under the guidance of a physician experienced with FH. If your doctor feels that you have FH, even if your genetic test result is negative, you should still be treated for high cholesterol.

What impact will genetic testing for FH have on family members?

If a patient tests positive (disease-causing variant identified), this means there is a 50% chance for an individual’s parents, siblings, and children to also have inherited this change. A genetic counselor can talk with you about this in more detail, and provide a discussion about how health information can be shared with family members so they are empowered to make informed healthcare decisions.

One of the potential benefits of genetic testing is determining that a family member has not inherited the FH gene. If there is no clinical diagnosis of FH, based on the LDL-C level and the family history, and especially if the FH gene has been found in other family members, then a negative test result can mean that the person did not inherit FH. This can be a tremendous relief for family members who might otherwise worry they had inherited the same “family history.”

Will a genetic test result change my treatment?

A genetic test result may change your treatment. Your healthcare provider may initiate medical therapy if they haven’t already, or choose to intensify the treatment by increasing the dose of your medication or adding additional medications. Some therapies may work better or worse depending on the specific genetic mutations. It is important that you discuss your results with your healthcare provider and determine the therapy that is right for you.

What if someone in my family has a positive genetic test result and normal LDL cholesterol?

It is possible for a person to have an FH phenotype and a negative genetic test for one of the known FH genes. It is also possible for a person to have a positive genetic test result for an FH gene, and have a normal LDL-C level. It is important to treat the risk, that is to treat the phenotype and lower the LDL-C level, even if a genetic variant is not found.

Patients with an FH gene, but with cholesterol levels in the normal range will likely have higher cholesterol in their lifespan then those without the FH gene. Having the LDL-C in the normal range is likely due to genetic interactions with genes that raise your cholesterol and genes that lower it. The good news is that with a lower LDL-C, your risk of a heart attack is much lower. However, your children could have high cholesterol if they do not also inherit the complimentary gene that lowers your cholesterol.

Phenotype vs. Genotype:

Phenotype: Observable physical or biochemical characteristics, such as high LDL-C and physical signs of FH, and personal or family history of early heart disease.
Genotype: A gene or set of genes a person carries.

Pathogenic Variants vs. Variants of Uncertain (Unknown) Significance (VUS):

Pathogenic Variant: A variant that is known to increase an individual’s susceptibility or predisposition to a certain disease or disorder.
Variant of Uncertain (Unknown) Significance (VUS): This is a variant that is identified with genetic testing, but researchers have not yet confirmed if this variant is a cause or risk factor for disease. A VUS remains on a kind of “watch list” as researchers learn more by studying the variant in other people, including family members, to see if it causes FH.