Familial Hypercholesterolemia

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.


> Ordering information for NGS panel


Indications for genetic testing:

  1. Confirmation of clinical diagnosis
  2. Carrier testing for known familial mutations
  3. Genetic counseling



Civeira F et al. Spanish Familial Hypercholesterolemia Group.; Tendon xanthomas in familial hypercholesterolemia are associated with cardiovascular risk independently of the low-density lipoprotein receptor gene mutation. Arterioscler Thromb Vasc Biol. 2005;25:1960–5.
Khachadurian AK, Uthman SM (1973). “Experiences with the homozygous cases of familial hypercholesterolemia. A report of 52 patients”. Nutr Metab 15 (1): 132–40.
Nordestgaard BG et al. European Atherosclerosis Society Consensus Panel.; Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease. Eur Heart J. 2013;34:3478–90.
Raal FJ, Santos RD. Homozygous familial hypercholesterolemia: Current perspectives on diagnosis and treatment. Atherosclerosis. 2012;223:262–8.
Rader DJ et al. Monogenic hypercholesterolemia: new insights in pathogenesis and treatment. J Clin Invest. 2003;111(12):1795–803.
Varret M et al. Genetic heterogeneity of autosomal dominant hypercholesterolemia. Clin Genet. 2008:73:1–13.