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Familial hypercholesterolemia (FH) is a dominantly inherited genetic disorder that affects about one in 250 individuals. Persons with this disorder have markedly elevated levels of low-density lipoprotein cholesterol (LDL-C or “bad” cholesterol) and accelerated rates of heart disease. Families with this disorder often have adults who have died of heart disease in their 40’s or 50’s. Persons with FH have a 2.5- to 10-fold increased risk of heart disease as compared to controls, but when FH is diagnosed and treated early in life, the risk is greatly reduced, often by as much as 80 percent. Unfortunately however, most people with FH have never been diagnosed or treated. Recently a new method of finding and treating those with FH has been developed. This new method is called family-based cascade screening.

Because FH is dominantly inherited, cascade screening of family members can be highly effective. Cascade screening relies on identifying an FH patient and then screening all potentially affected relatives using active cholesterol testing, genetic screening, or both. Then this cycle is repeated, or cascaded, for each relative diagnosed with FH, thereby expanding the number of potential cases identified. About 60 to 80 percent of those diagnosed with FH are found to have one or more genetic mutations. Other potential sources for identifying cases of FH include electronic medical records and billing code data.

Once an index patient with FH is found, cascade screening starts with first-degree relatives (parents, siblings, and children). If the affected parent is found, as many relatives on that parent’s side should be screened including children of the affected parent’s siblings. The children should be screened because treatment often begins in childhood. Cascade screening can reduce the average age at which FH is diagnosed and increase the number of individuals on lipid-lowering therapies, thereby reducing LDL-C and the rate of heart disease. For example, in the Netherlands cascade screening identified, on average, eight relatives with FH for each index case.

The main problem with cascade screening in the U.S. is identifying the index patient. Current estimates in the U.S. are that less than 10 percent of FH cases have been identified. Also lipid testing in children is not as common as adults, although a recent study showed the efficacy of screening children for FH during routine immunization visits (in the study for every 1000 children screened, eight with FH were identified). Another barrier to cascade screening in the U.S. is privacy laws. When an index case is identified, that person must reach out to all known relatives as privacy laws forbid the medical community to contact them.

From a patient perspective, it is important that the diagnosis of FH does not result in discrimination. In the U.S., the Genetic Information Nondiscrimination Act protects against health insurance and employment discrimination but unfortunately there is no current protection against life insurance or disability insurance bias.

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