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Hypercholesterolemia, autosomal dominant, type B(FHCL2)

MedGen UID:
309962
Concept ID:
C1704417
Disease or Syndrome
Synonyms: APOLIPOPROTEIN B-100, FAMILIAL DEFECTIVE; APOLIPOPROTEIN B-100, FAMILIAL LIGAND-DEFECTIVE; Familial hypercholesterolemia 2; Familial Hypercholesterolemia Type B; FHCL2; HYPERCHOLESTEROLEMIA, FAMILIAL, DUE TO LIGAND-DEFECTIVE APOLIPOPROTEIN B; Hyperlipoproteinemia Type IIb
SNOMED CT: Familial hyperlipoproteinemia type IIb (238040008); FCHL - Familial combined hyperlipidemia (238040008); Fredrickson type IIb hyperlipoproteinemia (238040008); Hyperapobetalipoproteinemia (238040008); FDB - Familial defective apolipoprotein B-100 (238081000); Familial defective apolipoprotein B-100 (238081000)
 
Gene (location): APOB (2p24.1)
 
Monarch Initiative: MONDO:0007751
OMIM®: 144010

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
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.

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.

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.  https://medlineplus.gov/genetics/condition/familial-hypercholesterolemia

Clinical features

From HPO
Coronary artery atherosclerosis
MedGen UID:
3623
Concept ID:
C0010054
Disease or Syndrome
Reduction of the diameter of the coronary arteries as the result of an accumulation of atheromatous plaques within the walls of the coronary arteries, which increases the risk of myocardial ischemia.
Hypercholesterolemia
MedGen UID:
5687
Concept ID:
C0020443
Disease or Syndrome
An increased concentration of cholesterol in the blood.
Increased LDL cholesterol concentration
MedGen UID:
154289
Concept ID:
C0549399
Finding
An elevated concentration of low-density lipoprotein cholesterol in the blood.
Xanthelasma
MedGen UID:
56357
Concept ID:
C0155210
Disease or Syndrome
The presence of xanthomata in the skin of the eyelid.
Arcus senilis
MedGen UID:
8179
Concept ID:
C0003742
Finding
A hazy, grayish-white ring about 2 mm in width located close to but separated from the limbus (the corneoscleral junction). Corneal arcus generally occurs bilaterally, and is related to lipid deposition in the cornea. Corneal arcus can occur in elderly persons as a part of the aging process but may be associated with hypercholesterolemia in people under the age of 50 years.

Professional guidelines

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
Santos RD
Curr Opin Cardiol 2019 Sep;34(5):526-530. doi: 10.1097/HCO.0000000000000660. PMID: 31393421
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
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
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
Santos RD
Curr Opin Cardiol 2019 Sep;34(5):526-530. doi: 10.1097/HCO.0000000000000660. PMID: 31393421
Defesche JC, Gidding SS, Harada-Shiba M, Hegele RA, Santos RD, Wierzbicki AS
Nat Rev Dis Primers 2017 Dec 7;3:17093. doi: 10.1038/nrdp.2017.93. PMID: 29219151
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
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
Makino H, Koezuka R, Tamanaha T, Ogura M, Matsuki K, Hosoda K, Harada-Shiba M
J Atheroscler Thromb 2019 Aug 1;26(8):679-687. Epub 2019 Jun 22 doi: 10.5551/jat.RV17033. PMID: 31231083Free PMC Article
Hajighasemi S, Mahdavi Gorabi A, Bianconi V, Pirro M, Banach M, Ahmadi Tafti H, Reiner Ž, Sahebkar A
Pharmacol Res 2019 May;143:119-132. Epub 2019 Mar 22 doi: 10.1016/j.phrs.2019.03.016. PMID: 30910740
Gencer B, Nanchen D
Curr Opin Lipidol 2016 Aug;27(4):375-81. doi: 10.1097/MOL.0000000000000311. PMID: 27092769

Clinical prediction guides

Alonso R, Argüeso R, Álvarez-Baños P, Muñiz-Grijalvo O, Diaz-Diaz JL, Mata P
Curr Atheroscler Rep 2022 Jun;24(6):427-434. Epub 2022 Apr 7 doi: 10.1007/s11883-022-01019-5. PMID: 35386090
Tokgozoglu L, Kayikcioglu M
Curr Cardiol Rep 2021 Sep 4;23(10):151. doi: 10.1007/s11886-021-01565-5. PMID: 34480646
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
Representatives of the Global Familial Hypercholesterolemia Community, Wilemon KA, Patel J, Aguilar-Salinas C, Ahmed CD, Alkhnifsawi M, Almahmeed W, Alonso R, Al-Rasadi K, Badimon L, Bernal LM, Bogsrud MP, Braun LT, Brunham L, Catapano AL, Cillíková K, Corral P, Cuevas R, Defesche JC, Descamps OS, de Ferranti S, Eiselé JL, Elikir G, Folco E, Freiberger T, Fuggetta F, Gaspar IM, Gesztes ÁG, Grošelj U, Hamilton-Craig I, Hanauer-Mader G, Harada-Shiba M, Hastings G, Hovingh GK, Izar MC, Jamison A, Karlsson GN, Kayikçioglu M, Koob S, Koseki M, Lane S, Lima-Martinez MM, López G, Martinez TL, Marais D, Marion L, Mata P, Maurina I, Maxwell D, Mehta R, Mensah GA, Miserez AR, Neely D, Nicholls SJ, Nohara A, Nordestgaard BG, Ose L, Pallidis A, Pang J, Payne J, Peterson AL, Popescu MP, Puri R, Ray KK, Reda A, Sampietro T, Santos RD, Schalkers I, Schreier L, Shapiro MD, Sijbrands E, Soffer D, Stefanutti C, Stoll M, Sy RG, Tamayo ML, Tilney MK, Tokgözoglu L, Tomlinson B, Vallejo-Vaz AJ, Vazquez-Cárdenas A, de Luca PV, Wald DS, Watts GF, Wenger NK, Wolf M, Wood D, Zegerius A, Gaziano TA, Gidding SS
JAMA Cardiol 2020 Feb 1;5(2):217-229. doi: 10.1001/jamacardio.2019.5173. PMID: 31895433
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
Ge X, Zhu T, Zeng H, Yu X, Li J, Xie S, Wan J, Yang H, Huang K, Zhang W
Biomed Res Int 2021;2021:8032978. Epub 2021 Oct 31 doi: 10.1155/2021/8032978. PMID: 34754882Free 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
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

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