It is estimated that less than 10% of cases of familial hypercholesterolemia (FH)
in the United States have been diagnosed. Low rates of diagnosis may in part be attributable
to affected patients not meeting the clinical diagnostic criteria of the Dutch Lipid
Clinic Network (DLCN), Simon Broome, or US MEDPED diagnostic criteria.
The objective of this study was to assess the utility of incorporating genetic testing
into a patient's evaluation for FH.
We retrospectively reviewed patients seen in the Advanced Lipids Disorders Clinic
at Johns Hopkins Hospital between January 2015 and May 2018. Between June 2018 and
December 2018, patients were consented to a prospective registry. DLCN, Simon Broome,
and MEDPED criteria were applied to each patient, before and after genetic testing.
Genetic testing included sequencing and deletion duplication analysis of four genes
(LDLR, PCSK9, APOB, and LDLRAP1).
The retrospective review and prospective study identified 135 adult probands who were
seen in our clinic for evaluation of heterozygous FH. Twenty-nine individuals (21%)
were heterozygous for a pathogenic or likely pathogenic monogenic variant. Before
genetic testing, using the DLCN criteria, 35 (26%) individuals met criteria for a
definite diagnosis of FH. Thirty patients (22%) met criteria using Simon Broome, and
29 (21%) patients met criteria using US MEDPED before genetic analysis. Depending
on the criteria, incorporating genetic testing identified 11–14 additional patients
Incorporating genetic testing diagnosed almost 50% more patients with definite FH
in comparison to classification solely on clinical grounds.