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Familial hypercholesterolemia(FH)

MedGen UID:
5688
Concept ID:
C0020445
Disease or Syndrome
Synonyms: Familial hypercholesterolemias; FH
SNOMED CT: Familial hypercholesterolemia (398036000); Essential familial hypercholesterolemia (398036000); Familial hyperbetalipoproteinemia (398036000); LDL receptor disorder (398036000); LDL - Low density lipoprotein receptor disorder (398036000); Low density lipoprotein catabolic defect (398036000); Hyperbetalipoproteinemia (190773008)
 
Genes (locations): APOB (2p24.1); LDLR (19p13.2); PCSK9 (1p32.3)
Related genes: LDLRAP1, PPP1R17, GHR, EPHX2, APOA2
 
Monarch Initiative: MONDO:0005439
OMIM® Phenotypic series: PS143890

Disease characteristics

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. [from GeneReviews]
Authors:
Hannah E Ison  |  Shoa L Clarke  |  Joshua W Knowles   view full author information

Additional description

From MedlinePlus Genetics
Familial hypercholesterolemia is an inherited condition characterized by very high levels of cholesterol in the blood. Cholesterol is a waxy, fat-like substance that is produced in the body and obtained from foods that come from animals (particularly egg yolks, meat, poultry, fish, and dairy products). The body needs this substance to build cell membranes, make certain hormones, and produce compounds that aid in fat digestion. In people with familial hypercholesterolemia, the body is unable to get rid of extra cholesterol, and it builds up in the blood. Too much cholesterol increases a person's risk of developing heart disease.

Familial hypercholesterolemia can also cause health problems related to the buildup of excess cholesterol in tissues other than the heart and blood vessels. If cholesterol accumulates in the tissues that attach muscles to bones (tendons), it causes characteristic growths called tendon xanthomas. These growths most often affect the Achilles tendons, which attach the calf muscles to the heels, and tendons in the hands and fingers. Yellowish cholesterol deposits can develop under the skin of the eyelids and are known as xanthelasmata. Cholesterol can also accumulate at the edges of the clear, front surface of the eye (the cornea), leading to a gray-colored ring called an arcus cornealis.

People with familial hypercholesterolemia have a high risk of developing a form of heart disease called coronary artery disease at a young age. This condition occurs when excess cholesterol in the bloodstream is deposited on the inner walls of blood vessels, particularly the arteries that supply blood to the heart (coronary arteries). The abnormal buildup of cholesterol forms clumps (plaques) that narrow and harden artery walls. As the plaques get bigger, they can clog the arteries and restrict the flow of blood to the heart. The buildup of plaques in coronary arteries causes a form of chest pain called angina and greatly increases a person's risk of having a heart attack.  https://medlineplus.gov/genetics/condition/familial-hypercholesterolemia

Recent clinical studies

Etiology

Tokgozoglu L, Kayikcioglu M
Curr Cardiol Rep 2021 Sep 4;23(10):151. doi: 10.1007/s11886-021-01565-5. PMID: 34480646
McGowan MP, Hosseini Dehkordi SH, Moriarty PM, Duell PB
J Am Heart Assoc 2019 Dec 17;8(24):e013225. Epub 2019 Dec 16 doi: 10.1161/JAHA.119.013225. PMID: 31838973Free PMC Article
Sharifi M, Futema M, Nair D, Humphries SE
Curr Cardiol Rep 2019 Apr 22;21(6):43. doi: 10.1007/s11886-019-1130-z. PMID: 31011892Free PMC Article
Benito-Vicente A, Uribe KB, Jebari S, Galicia-Garcia U, Ostolaza H, Martin C
Int J Mol Sci 2018 Nov 1;19(11) doi: 10.3390/ijms19113426. PMID: 30388787Free PMC Article
Maliachova O, Stabouli S
Curr Pharm Des 2018;24(31):3672-3677. doi: 10.2174/1381612824666181010145807. PMID: 30317987

Diagnosis

Tokgozoglu L, Kayikcioglu M
Curr Cardiol Rep 2021 Sep 4;23(10):151. doi: 10.1007/s11886-021-01565-5. PMID: 34480646
McGowan MP, Hosseini Dehkordi SH, Moriarty PM, Duell PB
J Am Heart Assoc 2019 Dec 17;8(24):e013225. Epub 2019 Dec 16 doi: 10.1161/JAHA.119.013225. PMID: 31838973Free PMC Article
Sharifi M, Futema M, Nair D, Humphries SE
Curr Cardiol Rep 2019 Apr 22;21(6):43. doi: 10.1007/s11886-019-1130-z. PMID: 31011892Free PMC Article
Maliachova O, Stabouli S
Curr Pharm Des 2018;24(31):3672-3677. doi: 10.2174/1381612824666181010145807. PMID: 30317987
Singh S, Bittner V
Curr Atheroscler Rep 2015;17(2):482. doi: 10.1007/s11883-014-0482-5. PMID: 25612857

Therapy

Tokgozoglu L, Kayikcioglu M
Curr Cardiol Rep 2021 Sep 4;23(10):151. doi: 10.1007/s11886-021-01565-5. PMID: 34480646
Raal FJ, Rosenson RS, Reeskamp LF, Hovingh GK, Kastelein JJP, Rubba P, Ali S, Banerjee P, Chan KC, Gipe DA, Khilla N, Pordy R, Weinreich DM, Yancopoulos GD, Zhang Y, Gaudet D; ELIPSE HoFH Investigators
N Engl J Med 2020 Aug 20;383(8):711-720. doi: 10.1056/NEJMoa2004215. PMID: 32813947
Raal FJ, Kallend D, Ray KK, Turner T, Koenig W, Wright RS, Wijngaard PLJ, Curcio D, Jaros MJ, Leiter LA, Kastelein JJP; ORION-9 Investigators
N Engl J Med 2020 Apr 16;382(16):1520-1530. Epub 2020 Mar 18 doi: 10.1056/NEJMoa1913805. PMID: 32197277
Bouhairie VE, Goldberg AC
Cardiol Clin 2015 May;33(2):169-79. doi: 10.1016/j.ccl.2015.01.001. PMID: 25939291Free PMC Article
Singh S, Bittner V
Curr Atheroscler Rep 2015;17(2):482. doi: 10.1007/s11883-014-0482-5. PMID: 25612857

Prognosis

Tokgozoglu L, Kayikcioglu M
Curr Cardiol Rep 2021 Sep 4;23(10):151. doi: 10.1007/s11886-021-01565-5. PMID: 34480646
Nohara A, Tada H, Ogura M, Okazaki S, Ono K, Shimano H, Daida H, Dobashi K, Hayashi T, Hori M, Matsuki K, Minamino T, Yokoyama S, Harada-Shiba M
J Atheroscler Thromb 2021 Jul 1;28(7):665-678. Epub 2021 Apr 18 doi: 10.5551/jat.RV17050. PMID: 33867421Free PMC Article
Lazarte J, Hegele RA
Can J Cardiol 2020 Sep;36(9):1362-1371. Epub 2020 Mar 23 doi: 10.1016/j.cjca.2020.03.020. PMID: 32640212
Sharifi M, Futema M, Nair D, Humphries SE
Curr Cardiol Rep 2019 Apr 22;21(6):43. doi: 10.1007/s11886-019-1130-z. PMID: 31011892Free PMC Article
Harada-Shiba M, Arai H, Ishigaki Y, Ishibashi S, Okamura T, Ogura M, Dobashi K, Nohara A, Bujo H, Miyauchi K, Yamashita S, Yokote K; Working Group by Japan Atherosclerosis Society for Making Guidance of Familial Hypercholesterolemia
J Atheroscler Thromb 2018 Aug 1;25(8):751-770. Epub 2018 Jun 7 doi: 10.5551/jat.CR003. PMID: 29877295Free PMC Article

Clinical prediction guides

Tokgozoglu L, Kayikcioglu M
Curr Cardiol Rep 2021 Sep 4;23(10):151. doi: 10.1007/s11886-021-01565-5. PMID: 34480646
Liberis A, Petousis S, Tsikouras P
Curr Pharm Des 2021;27(36):3804-3807. doi: 10.2174/1381612827666210421103245. PMID: 33882801
Nohara A, Tada H, Ogura M, Okazaki S, Ono K, Shimano H, Daida H, Dobashi K, Hayashi T, Hori M, Matsuki K, Minamino T, Yokoyama S, Harada-Shiba M
J Atheroscler Thromb 2021 Jul 1;28(7):665-678. Epub 2021 Apr 18 doi: 10.5551/jat.RV17050. PMID: 33867421Free PMC Article
Sharifi M, Futema M, Nair D, Humphries SE
Curr Cardiol Rep 2019 Apr 22;21(6):43. doi: 10.1007/s11886-019-1130-z. PMID: 31011892Free PMC Article
Turgeon RD, Barry AR, Pearson GJ
Can Fam Physician 2016 Jan;62(1):32-7. PMID: 26796832Free PMC Article

Recent systematic reviews

Chen R, Lin S, Chen X
J Clin Lab Anal 2022 Jul;36(7):e24552. Epub 2022 Jun 17 doi: 10.1002/jcla.24552. PMID: 35712827Free PMC Article
Barkas F, Nomikos T, Liberopoulos E, Panagiotakos D
Nutrients 2020 Aug 13;12(8) doi: 10.3390/nu12082436. PMID: 32823643Free PMC Article
Beheshti SO, Madsen CM, Varbo A, Nordestgaard BG
J Am Coll Cardiol 2020 May 26;75(20):2553-2566. doi: 10.1016/j.jacc.2020.03.057. PMID: 32439005
Ulven SM, Holven KB, Gil A, Rangel-Huerta OD
Adv Nutr 2019 May 1;10(suppl_2):S239-S250. doi: 10.1093/advances/nmy072. PMID: 31089732Free PMC Article
Turgeon RD, Barry AR, Pearson GJ
Can Fam Physician 2016 Jan;62(1):32-7. PMID: 26796832Free PMC Article

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • 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]

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