Fast Five Quiz: Heterozygous Familial Hypercholesterolemia Presentation and Diagnosis

Romesh Khardori, MD, PhD


December 22, 2021

The Dutch Lipid Clinic Network (DLCN) Score for FH is a widely used clinical scoring system to diagnose FH. Although it does include genetic data when available in its clinical scoring system, clinical criteria are not required to make a diagnosis of heterozygous FH. Lipid levels, physical examination findings, and family history are significant components in all of the various diagnostic scoring systems for FH. Of note, up to 60% of the patients with a clinical diagnosis of FH have no detectable genetic mutations; it is theorized that their phenotype may be due either to unknown FH-causing mutations or to a polygenic predisposition to severe hypercholesterolemia.

Lipoprotein electrophoresis is a costly procedure and is not required for a diagnosis of heterozygous FH to be made.

Cascade screening for FH via cholesterol testing, genetic analysis, or both has been shown to be very effective at reducing the age at which FH is diagnosed and increasing the percentage of individuals receiving lipid-lowering therapies. For example, cascade screening in the Netherlands identified an average of eight relatives with FH for each index case and significantly increased the proportion of patients with FH receiving treatment. In Spain, the SAFEHEART program showed that genetic screening identified patients at a younger age (median age, 49.5 years) and improved treatment initiation and adherence.

Although cholesterol measurement is routinely included in clinical cardiovascular risk assessment, it is not enough to effectively identify individuals at risk for heterozygous FH. Internationally, the use of recognized specialist diagnostic criteria, such as the DLCN, Simon Broome, or Make Early Diagnosis to Prevent Early Deaths (MEDPED) criteria, is recommended.

Learn more about the diagnosis of FH.


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