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GTR Home > Conditions/Phenotypes > Hypercholesterolemia, familial, 1


Excerpted from the GeneReview: Familial Hypercholesterolemia
Familial hypercholesterolemia (FH) is characterized by significantly elevated low-density lipoprotein cholesterol (LDL-C) that leads to atherosclerotic plaque deposition in the coronary arteries and proximal aorta at an early age and increases the risk of premature cardiovascular events such as angina and myocardial infarction; stroke occurs more rarely. Xanthomas (cholesterol deposits in tendons) may be visible in the Achilles tendons or tendons of the hands and worsen with age as a result of extremely high cholesterol levels. Xanthelasmas (yellowish, waxy deposits) can occur around the eyelids. Individuals with FH may develop corneal arcus (white, gray, or blue opaque ring in the corneal margin as a result of cholesterol deposition) at a younger age than those without FH. Individuals with a more severe phenotype, often as a result of biallelic variants, can present with very significant elevations in LDL-C (>500 mg/dL), early-onset coronary artery disease (CAD; presenting as early as childhood in some), and calcific aortic valve disease.

Genes See tests for all associated and related genes

  • Also known as: Apo-AII, ApoA-II, apoAII, APOA2
    Summary: apolipoprotein A2

  • Also known as: ABHD20, CEH, SEH, EPHX2
    Summary: epoxide hydrolase 2

  • Also known as: GHBP, GHIP, GHR
    Summary: growth hormone receptor

  • Also known as: FH, FHC, FHCL1, LDLCQ2, LDLR
    Summary: low density lipoprotein receptor

  • Also known as: C7orf16, GSBS, PPP1R17
    Summary: protein phosphatase 1 regulatory subunit 17

Clinical features


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Practice guidelines

  • ACMG ACT, 2019
    American College of Medical Genetics and Genomics, Genomic Testing (Secondary Findings) ACT Sheet, APOB, LDLR, PCSK9 Pathogenic Variants (Familial Hypercholesterolemia), 2019
  • CSANZ, 2016
    The Cardiac Society of Australia and New Zealand, Diagnosis and Management of Familial Hypercholesterolaemia – Position Statement
  • NICE, 2019
    National Institute for Health and Clinical Excellence, Identification and management of familial hypercholesterolaemia, 2008 [Updated: 4 October 2019]

Consumer resources

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