Purpose of review: Many international recommendations for the management of familial hypercholesterolaemia propose the use of cascade testing using the family mutation to unambiguously identify affected relatives. In the current economic climate DNA information is often regarded as too expensive. Here, we review the literature and suggest strategies to improve cost-effectiveness of cascade testing.
Recent findings: Advances in next-generation sequencing have both speeded up the time taken for a genetic diagnosis and reduced costs. Also, it is now clear that, in the majority of patients with a clinical diagnosis of familial hypercholesterolaemia in whom no mutation can be found, the most likely cause of their elevated LDL-cholesterol (LDL-C) is because they have inherited a greater number than average of common LDL-C raising variants in many different genes. The major cost driver for cascade testing is not DNA testing but treatment over the remaining lifetime of the identified relative. With potent statins now off-patent, the overall cost has reduced considerably, and combining these three factors, a familial hypercholesterolaemia service based around DNA-cascade testing is now less than 25% of that estimated by NICE in 2008.
Summary: Although all patients with a clinical diagnosis of familial hypercholesterolaemia need to have their LDL-C lowered, cascade testing should be focused on those with the monogenic form and not the polygenic form.