Genetic Testing Aids Diagnosis of Familial Hypercholesterolemia

By Will Boggs

March 25, 2020

NEW YORK (Reuters Health) - Adding genetic testing to the evaluation of patients at risk of familial hypercholesterolemia (FH) significantly increases the number of individuals diagnosed, according to a retrospective study.

"My main hope is that our data helps demonstrate to physicians and other healthcare providers that it is not always obvious whether or not a patient has familial hypercholesterolemia based solely on their medical and family history," Emily E. Brown of Johns Hopkins University, in Baltimore, Maryland, told Reuters Health by email. "Genetic testing can help clarify this and, in some cases, confirm a diagnosis."

Despite clear diagnostic criteria and guidelines recommending genetic testing, fewer than 10% of people with FH have been diagnosed with the condition.

Brown and colleagues assessed the utility of incorporating genetic testing into a patient's evaluation for FH in their review of 134 individuals with a history of hypercholesterolemia.

Overall, 45% of patients met either the Dutch Lipid Clinic Network (DLCN), Simon Broome, or U.S. MEDPED diagnostic criteria for FH, and 29 TO 35 individuals met criteria for FH prior to genetic testing, depending on which clinical diagnostic criteria were applied.

Pathogenic or likely pathogenic genetic variants were identified in 29 individuals (22%), and 23 of these individuals (79%) met the JACC 2018 consensus recommendations for when genetic testing should be offered.

Incorporating genetic testing identified five patients who would not have been identified using all three diagnostic criteria, the researchers report in the Journal of Clinical Lipidology.

Close to half of individuals with "probable FH" by DLCN criteria and almost a third with "possible FH" by Simon Broome criteria prior to genetic testing had positive genetic test results.

Similarly, 11 of 29 individuals who did not meet U.S. MEDPED criteria had positive genetic test results.

Nine patients who did not meet their insurance company criteria for a PCSK9 inhibitor prior to testing were eligible to obtain the medications after receiving a positive genetic test result.

Positive genetic test results also allowed for cascade screening for family members and in some cases changed medical management.

"I believe often patients aren't offered genetic testing for familial hypercholesterolemia because there is a misbelief that the genetic testing won't provide any additional, useful information," Brown said. "Hopefully, our study illustrates genetic testing often does provide important information regarding medical management for patients with very high cholesterol levels, and as a result this will help improve genetic testing rates in the future."

"Additionally," she said, "there is an outdated belief that genetic testing is very expensive and costs patients thousands of dollars out-of-pocket. While this can be the case depending on the genetic test this is ordered, many labs now offer genetic testing for familial hypercholesterolemia for a cash price of a few hundred dollars. Furthermore, many insurance policies do cover genetic testing for familial hypercholesterolemia if a patient meets their requirements. We need to increase healthcare providers' awareness that genetic testing often is no longer cost-prohibitive for many patients who may have this condition."

"Genetic testing can provide important information for patients and their families regarding their medical care," Brown concluded. "However, there are risks and limitations associated with genetic testing. I recommend patients speak with a healthcare provider who is well versed in genetics, such as a genetic counselor, prior to proceeding with genetic testing in order to review all of these nuances."

The study had no specific funding. Three of Brown's coauthors report ties to companies selling cholesterol-lowering drugs.

In a separate report in the same journal, Dr. Samuel S. Gidding from FH Foundation, Pasadena, California described the uptake of genetic testing for FH when cost and privacy issues were removed.

Of 435 eligible individuals included in the study, 147 opted in to participate in genetic testing, 122 consented, and 110 ultimately received testing.

Overall, 64 participants (58.2%) had a positive genetic test result for a pathogenic variant in LDLR or APOB, and 11 had a variant of uncertain significance.

"Genetic testing provides important diagnostic information about genetic lipid conditions, particularly familial hypercholesterolemia," Dr. Gidding told Reuters Health by email. "Physicians should learn more about genetic testing, use referrals to genetics counselors, and also learn more about proper ways to communicate results of genetic testing, particularly negative results, as these also have health implications."

Katherine Wilemon, founder and CEO of the FH Foundation and a study coauthor, told Reuters Health by email, "Our study found that individuals with clinically diagnosed familial hypercholesterolemia (FH) were interested and willing to get genetic testing when barriers were removed. However, this did not translate to an uptake in first-degree family members getting genetically screened for FH despite there being a 50% chance of each of these relatives having inherited this genetic condition."

Dr. Gerald F. Watts of the University of Western Australia, in Perth, who recently reviewed genetic testing in FH, told Reuters Health by email, "Patients can be effectively managed without genetic testing, but this test has prognostic value and makes family tracing more cost-effective."

Dr. Watts, who was not involved in the new studies, also cautioned, "You cannot rule out FH if you do not identify a mutation."

SOURCE: and Journal of Clinical Lipidology, online March 2 and February 11, 2020.


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