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.

Bioinformatics Genomics England Queen Mary University of London London United Kingdom

Central European Institute of Technology Masaryk University Brno Czech Republic; Centre for Cardiovascular Surgery and Transplantation Brno Czech Republic

Department of Cardiology Boston Children's Hospital and Harvard Medical School Boston Massachusetts

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

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

Department of Clinical Genetics Academic Medical Center at the University of Amsterdam Amsterdam the Netherlands

Department of Internal Medicine Erasmus Medical Center Rotterdam the Netherlands

Department of Internal Medicine University of Texas Southwestern Medical Center Dallas Texas

Department of Internal Medicine Wexner Medical Center at The Ohio State University Columbus Ohio

Department of Medicine Baylor College of Medicine Houston Texas

Department of Medicine Division of Cardiology Department of Genetics McDonnell Genome Institute Washington University School of Medicine St Louis Missouri

Department of Medicine Division of Cardiovascular Medicine and Cardiovascular Institute Stanford University Stanford California; The Familial Hypercholesterolemia Foundation Pasadena California

Department of Molecular Innovation in Lipidology National Cerebral and Cardiovascular Center Research Institute Osaka Japan

Department of Vascular Medicine Academic Medical Center Amsterdam the Netherlands

Division of Translational Medicine and Human Genetics Department of Medicine Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania

Fundación Hipercolesterolemia Familiar Madrid Spain

Genomic Medicine Institute Geisinger Danville Pennsylvania

Lipid Clinic Heart Institute University of São Paulo Medical School Hospital and Hospital Israelita Albert Einstein São Paulo Brazil

Medicine and Pharmacology Vanderbilt University School of Medicine Nashville Tennessee

Nemours Cardiac Center A 1 DuPont Hospital for Children Wilmington Delaware

Sorbonne Université and Centre de Génétique Moléculaire et Chromosomique unité de Génétique de l'Obésitéet des dyslipidémies Hôpital de la Pitié Salpêtrière Paris France

The Familial Hypercholesterolemia Foundation Pasadena California

The Familial Hypercholesterolemia Foundation Pasadena California; Department of Integrated Medical Sciences Charles E Schmidt College of Medicine Florida Atlantic University Boca Raton Florida

The Familial Hypercholesterolemia Foundation Pasadena California; Department of Pediatrics West Virginia University Morgantown West Virginia

The Familial Hypercholesterolemia Foundation Pasadena California; Departments of Genetics Medicine and Pediatrics Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania

Unidade 1 and 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 and Integrative Sciences Institute Lisboa Portugal

References provided by Crossref.org

Worldwide experience of homozygous familial hypercholesterolaemia: retrospective cohort study

Genetics of Cardiovascular Disease: How Far Are We from Personalized CVD Risk Prediction and Management?

Genetics of Familial Hypercholesterolemia: New Insights