Clinical experience of scoring criteria for Familial Hypercholesterolaemia (FH) genetic testing in Wales

- Scoring criteria have been developed to select patients for DNA testing for FH.
- 623 patients presenting to lipid clinics across Wales had DNA testing.
- 85% scoring 15 had a mutation compared to 4% in those scoring 5 or less.
- These criteria are a useful tool for the diagnosis of Familial Hypercholesterolaemia.

Background/ObjectiveFamilial Hypercholesterolaemia (FH) is caused by mutations in genes of the Low Density Lipoprotein (LDL) receptor pathway. A definitive diagnosis of FH can be made by the demonstration of a pathogenic mutation. The Wales FH service has developed scoring criteria to guide selection of patients for DNA testing, for those referred to clinics with hypercholesterolaemia. The criteria are based on a modification of the Dutch Lipid Clinic scoring criteria and utilise a combination of lipid values, physical signs, personal and family history of premature cardiovascular disease. They are intended to provide clinical guidance and enable resources to be targeted in a cost effective manner.Methods623 patients who presented to lipid clinics across Wales had DNA testing following application of these criteria.ResultsThe proportion of patients with a pathogenic mutation ranged from 4% in those scoring 5 or less up to 85% in those scoring 15 or more. LDL-cholesterol was the strongest discriminatory factor. Scores gained from physical signs, family history, coronary heart disease, and triglycerides also showed a gradient in mutation pick-up rate according to the score.ConclusionThese criteria provide a useful tool to guide selection of patients for DNA testing when applied by health professionals who have clinical experience of FH.

The proportion of patients with a pathogenic mutation for FH (class 5) was strongly related to the score derived from these criteria in 623 patients presenting to Lipid Clinics across Wales.137