Familial Hypercholesterolaemia Genetic Testing Pathway

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The East Genomic Laboratory Hub Familial Hypercholesterolaemia Genetic Testing Pathway provides guidance for healthcare professionals with patients with a high likelihood of FH.

Download FH Genetic Testing Pathway FAQs

The Test Order form can be completed electronically or printed and completed by hand. To complete electronically, please download the PDF form above onto your computer and open in Adobe software to enable electronic editing.

FH Diagnostic Genetic Testing

The National Genomics Test Directory eligibility criteria for Familial Hypercholesterolaemia genetic testing are:

an age adjusted FHWales (opens in a new tab) score or a Dutch Lipid Clinic Score (opens in a new tab) > 5 OR
the Simon Broome criteria (opens in a new tab) (for definite or possible FH) OR
there are special circumstances, such as adoption, where the family history cannot be ascertained

It is essential to indicate on the test order form if the patient is positive for the Simon Broome criteria, OR to provide the FHWales / Dutch Lipid Clinic Score.

Where test orders are incomplete or the information provided does not support eligibility for testing, the sample will be extracted and stored and the East GLH will issue a report indicating the reason for non-acceptance of testing.

FH Cascade Genetic Testing

Genetic testing is recommended for first and second degree relatives of patients with a known FH causing genetic variant.

Test orders for cascade testing must include the details of the index patient and the genetic variant found in the family. Where this information is not provided, the sample will be extracted and stored and the East GLH will issue a report indicating the reason for non-acceptance of testing.

Consent Discussion about Genetic Testing

An appropriate discussion of genetic testing and the possible implications for a patient and their family members should take place prior to testing.

The East Genomic Laboratory Hub FH Test Order form includes a section to help guide this conversation.

A record of the consent discussion should be stored in the patient's clinical record.

Consent Discussion for FH Diagnostic testing

The FH test will look for genetic variants in only the genes known to cause FH.

The East GLH Laboratory will extract DNA from the patients sample and analyse the DNA sequence of five genes known to contain genetic variants that cause FH.

The FH test may not identify a genetic cause of FH. This does not exclude a diagnosis of FH.

A genetic diagnosis is identified in approximately 80% of patients with a high likelihood of FH. There may be other genetic causes of FH that we do not know about and some individuals have high lipid levels due to multiple genetic factors that each have a small effect. This is sometimes known as polygenic FH. Testing for polygenic high lipid levels/FH is not currently a test commissioned by NHS England.

The FH test results may be uncertain and change over time.

Some genetic variants in patients are very rare and without additional evidence the Clinical Scientist may report these as “variants of uncertain significance”. Through the identification of additional patients with the same genetic variant or cell function studies the strength of evidence for causality may increase and be reinterpreted as Likely Pathogenic.

The FH test results may have implications for other family members.

FH is usually an autosomal dominant genetic disorder. This means that, first degree relatives of a patient with FH will have a 50% chance of also being affected.

Research Opportunities

The East Genomics team aim to carry out research studies in the future to better understand the genetics of FH, high lipid levels and cardiovascular disease. Indicate on the form if the patient does or does not wish to receive information about opportunities to take part in research.

Consent Discussion for contact for research studies

Research studies may lead to improvements in the diagnosis and treatment of Familial Hypercholesterolaemia, high lipid levels and cardiovascular disease.

This patient is under no obligation to take part in any research studies.

If a patient is contacted with information about a study, they are under no obligation to take part.

This decision will not affect the care this patient will receive.