Fast Five Quiz: Heterozygous Familial Hypercholesterolemia Presentation and Diagnosis

Romesh Khardori, MD, PhD


February 15, 2023

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 of relatives has been given a Tier 1 classification by the US Centers for Disease Control and Prevention because of its efficacy. Past studies have successfully implemented either universal or opportunistic pediatric lipid screening, leading to the diagnosis of FH in parents and siblings of patients. The DECOPIN project documented the efficacy of diagnosing FH among children whose parents were diagnosed with definite FH. In addition, a recent pragmatic clinical trial concluded that the new FH case detection rate was significantly higher in families with a monogenic etiology of FH vs families without this etiology, thanks to more frequent use of cascade testing.

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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