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J Am Coll Cardiol. 2018 Aug 7;72(6):662-680. doi: 10.1016/j.jacc.2018.05.044.

Clinical Genetic Testing for Familial Hypercholesterolemia: JACC Scientific Expert Panel.

Author information

1
Genomic Medicine Institute, Geisinger, Danville, Pennsylvania. Electronic address: asturm@geisinger.edu.
2
Department of Medicine, Division of Cardiovascular Medicine, and Cardiovascular Institute, Stanford University, Stanford California; The Familial Hypercholesterolemia Foundation, Pasadena, California.
3
Nemours Cardiac Center, A.I. DuPont Hospital for Children, Wilmington, Delaware.
4
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
5
The Familial Hypercholesterolemia Foundation, Pasadena, California.
6
Department of Medicine, Baylor College of Medicine, Houston, Texas.
7
The Familial Hypercholesterolemia Foundation, Pasadena, California; Department of Integrated Medical Sciences, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida.
8
Unidade I&D, Grupo de Investigação Cardiovascular, Departamento de Promoção da Saúde e Doenças Não Transmissíveis, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa, Portugal; University of Lisboa, Faculty of Sciences, BioISI-Biosystems & Integrative Sciences Institute, Lisboa, Portugal.
9
Sorbonne Université and Centre de Génétique Moléculaire et Chromosomique, unité de Génétique de l'Obésitéet des dyslipidémies, Hôpital de la Pitié-Salpêtrière, Paris, France.
10
Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
11
Department of Cardiology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.
12
Department of Clinical Genetics, Academic Medical Center at the University of Amsterdam, Amsterdam, the Netherlands.
13
Central European Institute of Technology, Masaryk University, Brno, Czech Republic; Centre for Cardiovascular Surgery and Transplantation, Brno, Czech Republic.
14
Department of Internal Medicine, Wexner Medical Center at The Ohio State University, Columbus, Ohio.
15
Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
16
Bioinformatics, Genomics England, Queen Mary University of London, London, United Kingdom.
17
Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee.
18
Fundación Hipercolesterolemia Familiar, Madrid, Spain.
19
The Familial Hypercholesterolemia Foundation, Pasadena, California; Department of Pediatrics (Cardiology), West Virginia University, Morgantown, West Virginia.
20
Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
21
Lipid Clinic Heart Institute (InCor) University of São Paulo Medical School Hospital and Hospital Israelita Albert Einstein, São Paulo, Brazil.
22
Department of Molecular Innovation in Lipidology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan.
23
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
24
Department of Medicine, Division of Cardiology, Department of Genetics, McDonnell Genome Institute, Washington University School of Medicine, St. Louis, Missouri.
25
Department of Cardiovascular Medicine, Rinku General Medical Center, Osaka, Japan; Departments of Community Medicine and Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
26
Genomic Medicine Institute, Geisinger, Danville, Pennsylvania.
27
The Familial Hypercholesterolemia Foundation, Pasadena, California; Departments of Genetics, Medicine, and Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.

Abstract

Although awareness of familial hypercholesterolemia (FH) is increasing, this common, potentially fatal, treatable condition remains underdiagnosed. Despite FH being a genetic disorder, genetic testing is rarely used. The Familial Hypercholesterolemia Foundation convened an international expert panel to assess the utility of FH genetic testing. The rationale includes the following: 1) facilitation of definitive diagnosis; 2) pathogenic variants indicate higher cardiovascular risk, which indicates the potential need for more aggressive lipid lowering; 3) increase in initiation of and adherence to therapy; and 4) cascade testing of at-risk relatives. The Expert Consensus Panel recommends that FH genetic testing become the standard of care for patients with definite or probable FH, as well as for their at-risk relatives. Testing should include the genes encoding the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9); other genes may also need to be considered for analysis based on patient phenotype. Expected outcomes include greater diagnoses, more effective cascade testing, initiation of therapies at earlier ages, and more accurate risk stratification.

KEYWORDS:

cascade testing; consensus statement; familial hypercholesterolemia; genetic counseling; genetic testing

PMID:
30071997
DOI:
10.1016/j.jacc.2018.05.044

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