At present, FH is primarily (but not exclusively) considered to be a receptor disease. It is a monogenic disease transmitted through autosomal dominant inheritance, and stems from either an LDL-R defect, or FDB, in cases of PCSK9 mutations.
FH is an example of a disease that, by its very nature, allows us study the relationship between lipid metabolism, especially LDL-C, and atherosclerosis, as well as premature manifestation of cardiovascular disease. Unfortunately, and most importantly, it is also the most significant clinical syndrome which, through congenitally elevated LDL-C concentrations, leads to the development of CAD.
Familial hypercholesterolemia (FH) occurs with a frequency of 1:250 – 1:500 and is one of the most common congenital metabolic disorders. It is a monogenic handicap wherein the defect of a single gene essentially determines the resulting form of the disease. Hypercholesterolemia is typically present from birth, and the risk for manifesting premature atherosclerosis is very high.
FH is characterized by an autosomal dominant inheritance pattern; i.e. the disease is present in a parent, one of the grandparents, statistically half of the siblings, and statistically half of the offspring of the affected proband. In the event that one of the parents had heterozygous FH, there is a 50% probability that the offspring will also have FH.