Did You Know: Familial hypercholesterolemia

Familial hypercholesterolemia (FH) is the most common inherited cardiovascular disease. FH often remains undiagnosed and untreated, leading to early heart attacks and heart disease. The genetic changes seen in FH affect how cholesterol is cleared from the body and leads to high amounts of low density lipoprotein (LDL), also referred to as bad cholesterol. When there is too much bad cholesterol in the bloodstream, it can build up on the artery walls in the form of plaques and harden. This condition is called atherosclerosis and accounts for 2-3% of heart attacks in individuals younger than 60 years old.¹

FH is inherited in an autosomal dominant manner, meaning that once someone is identified as having FH, there is a 50% chance that each of their children will  inherit the condition. Although less likely, there are cases where people have FH without having an affected parent. When one individual with FH is diagnosed in a family, it is important that other family members be screened for FH. 70%-95% of FH are due to mutations in APOB, LDLR, or PCSK9.²

Treatment for affected individuals should begin early. Although lifestyle and diet are important factors to staying healthy, they are not sufficient for individuals with FH.

Reasons for Genetic Testing

• Confirmation of a clinical diagnosis through genetic testing can direct medical management (e.g., the ability to use PCSK9 inhibitors) and may help predict the progression and severity of the disease
• Identification of one affected individual allows for very important screening of at-risk family members (referred to as cascade screening)
• Knowledge of at-risk family members provides information about potential age of onset, reproductive risks, preconception/prenatal options, and appropriate referral for patient support and resources

Who may benefit from this test?

• Individuals with a positive family history of familial hypercholesterolemia
• Individuals with family history of early heart disease and/or heart attacks
• Individuals with high levels of LDL-cholesterol that do not decrease with diet and exercise

LifeLabs Genetics offers the following FH next-generation sequencing panel (sequencing and copy number variant analyses)

• Familial Hypercholesterolemia: APOB, LDLR, PCSK9, GHR

LifeLabs Genetics also offers additional cardiology-related, next-generation sequencing panels (sequencing and copy number variant analyses)

• Combined Arrhythmia Panel: AKAP9, ANK2, CACNA1C, CACNB2, CALM1, CALM2, CALM3, CASQ2, CAV3, CDH2, CTNNA3, DES, DSC2, DSG2, DSP, GPD1L, HCN4, JUP, KCNA5, KCND3, KCNE1, KCNE2, KCNE3, KCNH2, KCNJ2, KCNJ5, KCNQ1, LMNA, NPPA, PKP2, PLN, RYR2, SCN1B, SCN3B, SCN4B, SCN5A, SLMAP, SNTA1, TGFB3, TMEM43, TRDN, TTN
  • Includes: Hereditary Arrhythmia, Long and Short QT Syndromes, Brugada Syndrome, CPVT, ARVC
• Combined Cardiomyopathy Panel: ABCC9, ACTC1, ACTN2, ANKRD1, BAG3, BRAF, CALR3, CAV3, CBL, CRYAB, CSRP3, DES, DMD, DNAJC19, DOLK, DSC2, DSG2, DSP, EMD, EYA4, FHL2, FKTN, FLNC, GATA4, GATAD1, GLA, HRAS, JPH2, KAT6B, KRAS, LAMA4, LAMP2, LDB3, LMNA, LZTR1, MAP2K1, MAP2K2, MYBPC3, MYH6, MYH7, MYL2, MYL3, MYLK2, MYPN, NEBL, NEXN, NF1, NRAS, PDLIM3, PKP2, PLN, PRDM16, PRKAG2, PTPN11, RAF1, RASA2, RBM20, RIT1, SCN5A, SGCD, SHOC2, SLC25A4, SOS1, SOS2, SPRED1, TAZ, TBX20, TCAP, TNNC1, TNNI3, TNNT2, TPM1, TRIM63, TTN, TTR, VCL
  • Includes: ARVC, Hypertrophic Cardiomyopathy, Dilated Cardiomyopathy, Noonan and related RASopathies
• Combined Aortopathies and Connective Tissue Disorders Panel: ABCC6, ACTA2, ACVR1, ADAMTS2, ALDH18A1, ATP6V0A2, ATP7A, B3GALT6, B3GAT3, B4GALT7, BGN, CBS, CHST14, COL11A1, COL11A2, COL12A1, COL1A1, COL1A2, COL2A1, COL3A1, COL4A1, COL4A3, COL4A4, COL4A5, COL5A1, COL5A2, COL9A1, COL9A2, COL9A3, DSE, EFEMP2, ELN, FBLN5, FBN1, FBN2, FKBP14, FLNA, GORAB, LOX, LTBP4, MAT2A, MED12, MFAP5, MYH11, MYLK, NOTCH1, PLOD1, PRDM5, PYCR1, RIN2, SKI, SLC2A10, SLC39A13, SMAD2, SMAD3, SMAD4, TGFB2, TGFB3, TGFBR1, TGFBR2, TNXB, ZNF469
  • Includes: Familial Thoracic Aortic Aneurysm, Ehlers Danlos Syndrome, Marfan Syndrome, Loeys-Dietz Syndrome, Alport and Stickler Syndromes

References

1. Nordestgaard 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: consensus statement of the European Atherosclerosis Society. Eur Heart J. 2013;34:3478–90a.
2. Youngblom et al. Familial Hypercholesterolemia. GeneReviews®. Pagon RA, Adam MP, Ardinger HH, et al., editors. Seattle (WA): University of Washington, Seattle; 1993-2017. Last uupdate 2016.