Description of Medical ServiceThe investigative purpose of genetic testing for heritable (inherited) mutations, which are in scope for this Clinical Utility Card (CUC) are:
(a) Clinically-affected individuals, in order to make a genetic diagnosis and estimate a person’s likely future risk of further disease – this is also called diagnostic testing; and
(b) Cascade testing of family members of those people who tested positive to one or more relevant mutations, in order to make a genetic diagnosis and estimate each family member’s risk in developing the disease (and, less commonly, the risk of further disease if the disease has already been diagnosed) – this is also called predictive testing.
For each disease area, ‘star performer’ gene(s) for are selected for testing on the basis of having the strongest case for clinical usefulness. Evidence provided in the CUC focusses on these ‘star performer’ genes. Other genes may be added to the panel of genes tested if they also have clinical usefulness; if they do not interfere with clinical usefulness of ‘star performer’ genes; and if they only have minor consequences for incremental cost-effectiveness of the proposed genetic testing. Evidence provided in the CUC for these other genes is less than the ‘star performer’ genes.
For each disease area, the characteristics of clinically-affected people who should be eligible for this genetic testing are defined. This reflects an MSAC preference for low probability of an actionable result over a high probability of an uninterpretable or unactionable result. Cascade testing is then only contemplated for family members of people who test positive to a relevant mutation, and only when this mutation is associated with having clinical usefulness for family members.
Description of Medical ConditionFamilial hypercholesterolaemia (FH) is a genetic condition where a person inherits high cholesterol. The genetic disorder results in increased levels of total blood cholesterol and low density lipoprotein cholesterol (LDL-C). LDL-C is deposited in body tissues and blood vessels, and results in early cardiovascular disease and premature death. Although untreated (severe) FH is clinically obvious, milder forms of the disease are more difficult to identify. This is because cholesterol deposits in body tissues take time to develop, may be hidden by partial therapy, or not detected as FH.
Genetic testing to confirm an FH diagnosis (in patients who are suspected as having inherited their high blood cholesterol) allows cascade testing to be conducted in family members. Half of these family members (50%) are also likely to have FH, and detection of them early in life will allow lifestyle changes and drug therapy to lower their blood cholesterol and therefore prevent/reduce the severity of cardiovascular disease. The other 50% of family members will be reassured that they don’t have the inherited condition.