What is the definition of Familial Hypercholesterolemia?

Familial hypercholesterolemia is a condition characterized by very high levels of cholesterol in the blood due to mutations in the LDLR gene. People with hypercholesterolemia have a high risk of developing a form of heart disease called coronary artery disease, as well as health problems related to the buildup of excess cholesterol in other tissues (e.g., in the tendons and skin). Familial hypercholesterolemia tends to be passed through families in an autosomal dominant fashion. There are other hereditary forms of hypercholesterolemia caused by mutations in the APOB, LDLRAP1, or PCSK9 gene. However, most cases of high cholesterol are not caused by a single inherited condition, but result from a combination of lifestyle choices and the effects of variations in many genes.

What are the alternative names for Familial Hypercholesterolemia?

  • HYPERLIPOPROTEINEMIA, TYPE II
  • Hyperlipoproteinemia type IIA
  • Hyper-low density-lipoproteinemia
  • Familial hypercholesterolemic xanthomatosis

What are the symptoms for Familial Hypercholesterolemia?

Signs and symptoms in individuals with the autosomal dominant form of familial hypercholesterolemia (FH), also called the heterozygous form, may include:

  • Elevated total and LDL cholesterol levels
  • Coronary heart disease which can cause angina (heart pain), nonfatal or fatal heart attacks, need for angioplasty, or sudden death
  • Cerebrovascular disease which may cause stroke or transient ischemic attack (TIA)
  • Peripheral vascular disease which may cause pain when walking that is relieved by rest
  • Aortic aneurysm that may rupture, causing catastrophic bleeding and often death
  • Xanthomas (firm nodules under the skin caused by deposition of cholesterol on tendons)
  • Corneal arcus (an opaque, white line within the margin of the cornea that is above or surrounds the cornea)
  • Xanthelasmas (cholesterol deposits on, above or under the eyelids)

Men who have FH may have heart attacks in their 40s to 50s, and 85% of men with the disorder have a heart attack by age 60. Affected women may have heart attacks in their 50s and 60s.

Individuals with the rare, autosomal recessive form of FH (also called homozygous FH) develop xanthomas beneath the skin over their elbows, knees and buttocks as well as in the tendons at a very early age, sometime in infancy. In individuals with this form of FH, heart attacks and/or death may occur before age 30, sometimes in young children if they are not aggressively treated.

Is Familial Hypercholesterolemia an inherited disorder?

Familial hypercholesterolemia (FH) is usually inherited in an autosomal dominant manner (in which case it is referred to as heterozygous FH). Individuals inherit two copies of each gene (one from each parent). In an autosomal dominant condition, having only one abnormal (mutated) copy of the gene is sufficient to cause the condition. In most cases the mutated gene is inherited from an affected parent, but it is possible for the mutation to occur for the first time in the affected individual. An individual with an autosomal dominant condition has a 50% (1 in 2) chance to pass the mutation on to each of his/her children and a 50% chance to not pass on the mutation. In rare cases, a person inherits a mutated copy of the gene from both parents (this is also called homozygous FH). This is a much more severe form of FH. An individual with this form of FH will always pass on a mutated copy of the gene, and therefore each of his/her children will have heterozygous FH.