The importance of cascade genetic screening for diagnosing autosomal dominant hypercholesterolemia: Results from twenty years of a national screening program in Norway

Background: The most cost-effective strategy to diagnose patients with autosomal dominant hypercholesterolemia (ADH) is to perform cascade genetic screening. Objective: To present the cascade genetic screening program for ADH in Norway. Methods: A national cascade genetic screening program for ADH in Norway has been operating at Unit for Cardiac and Cardiovascular Genetics, Oslo University Hospital for twenty years. This program has been run by just one genetic counsellor. We now present the main findings of this cascade genetic screening program. Results: After genetic counselling, 8182 at-risk relatives have consented to genetic testing for the mutation that causes ADH in the family. Of these, 3076 (37.6%) relatives have tested positive. Among mutation-positive relatives 31.3% were on lipid-lowering therapy at the time of genetic testing. However, only 9.8% of these relatives had a value for low density lipoprotein (LDL) cholesterol below 2.5 mmol/l (97 mg/dl). At follow-up six months after genetic testing, reductions in the levels of total serum cholesterol and LDL cholesterol of 12% and 17%, respectively were observed. A total of 8811 ADH heterozygotes have been diagnosed in Norway. Thus, the number of patients diagnosed by this modest cascade genetic screening program constitutes 35% of all Norwegian ADH patients provided with a molecular genetic diagnosis. Conclusion: Cascade genetic screening for ADH is very effective and should be organized at a national level. Even a modest cascade genetic screening program with small resources, can result in a large number of patients being identified. (c) 2021 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Automated summary

The cascade genetic screening program for autosomal dominant hypercholesterolemia in Norway has been running for 20 years and has been successful in identifying a significant number of at-risk relatives. Despite a high proportion of mutation-positive relatives undergoing lipid-lowering therapy, a large number still had suboptimal LDL cholesterol levels.