Familial hypercholesterolemia (FH) is characterized by high LDL (low density lipoprotein) cholesterol level that cause atherosclerotic plaque deposition in the coronary arteries, increasing the risk for early cardiovascular disease and stroke.
Deposition of cholesterol is also found in the tendons of the hands, elbows, knees and feet (xanthomas) and around the eyes (xanthelasmas).
Heterozygous FH is associated with heterozygous pathogenic variant in one of three genes – LDLR, APOB, PCSK9, and occurs at a frequency of about 1:500. Homozygous FH is much rarer, occurring in about 1:1,000,000 in general population. Homozygous FH results from biallelic mutations in one of the following genes: LDLR, LDLRAP1, APOB, PCSK9.
Indications for genetic testing:
- Confirmation of clinical diagnosis
- Carrier testing for known familial mutations
- Genetic counseling
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