What is being tested?

LDL (Low Density Lipoprotein) cholesterol is the 'bad' cholesterol; it increases the risk of cardiovascular disease. The body's cells, particularly the liver cells, take up the LDL cholesterol from blood via LDL-receptors. Normally a person has two working copies of the gene encoding the LDL-receptor (one copy inherited from their mother and one from their father), but in FH one copy is defective, so only half of the normal numbers of LDL-receptors are produced. This results in LDL cholesterol accumulating in blood and around the body, including the artery walls (known as atherosclerosis) and increasing risk of early heart disease. FH is a 'dominant' genetic disorder, meaning having a single defective gene causes FH.

Worldwide, about 1 in 250 people have FH caused by a 'mutation'. or 'variant', in the LDL-receptor or in another gene involved in the clearance of LDL particles from the blood.

There are two types of FH genetic testing:

•  A test looking at a person's DNA to search for any variant in the FH-causing genes.
• A test looking at a person's DNA for just a specific variant that has previously been identified in their family.

How is it used?

FH genetic testing is used to confirm a diagnosis of FH. For a given LDL cholesterol level, people who have an FH-causing genetic variant are at a higher cardiovascular disease risk than those without an FH-causing variant. Those with FH may be monitored more closely and treated more aggressively with cholesterol-lowering therapy.

People diagnosed with FH may be eligible for PCSK9 inhibitor therapy.

When is it requested?

FH genetic testing for an 'index case' (the person identified in their family with the condition) is requested by a specialist if they suspect a person's high LDL cholesterol is due to FH. Features that increase the likelihood of FH include early heart or vascular disease (before age 55 years in men and before age 60 years in women), cholesterol deposits in the tendons (xanthomata) or eyes (arcus cornealis), and a strong family history of high cholesterol or premature heart disease. A calculated score called the Dutch Lipid Clinic Network Score, based on the individual's family history, untreated LDL-cholesterol levels and physical signs, is used to determine whether FH is likely. The DLCNC score can be calculated at here.

What does the result mean?

Possible outcomes of genetic testing include:

• A disease-causing (pathogenic), or likely disease-causing (likely pathogenic), genetic variant is identified. This confirms the diagnosis of FH.
• A disease-causing variant was not identified. This may be because the high cholesterol is not due to a genetic change, is due to a genetic change(s) in a gene(s) not analysed in this test, or is due to a change in one of the genes analysed for the technical reasons the test method was unable to detect it. This result does not mean that the person does not have FH.
• A variant of uncertain significance is identified. This means that based on current knowledge of the gene involved, the laboratory is unable to determine whether the genetic change is the cause of the high cholesterol.

Is there anything else I should know?

FH genetic testing is not available in many laboratories. Your specimen may need to be sent away to a specialist reference laboratory, and the results may take weeks to months before they are available.

Common questions

• I have FH. Will my child/ family members have FH?

FH is a dominantly inherited genetic disorder. If you have FH confirmed by genetic testing, each of your first degree family members (parents, siblings, and children) has a 50% chance of also having the gene variant causing FH.

• Is FH genetic testing covered by Medicare?

As of 1st May 2020, yes - FH genetic testing may be ordered for testing an ‘index case’ by a specialist (73352) or for testing first or second degree relatives of a patient with an FH-causing variant by their GP or specialist (73353).

More information

FH Australasia Network

FH Calculator (Dutch Lipid Clinic Network Score)

International FH Foundation