Clinical Genetic Testing for Familial Hypercholesterolemia: JACC Scientific Expert Panel
Amy C Sturm, Joshua W Knowles, Samuel S Gidding, Zahid S Ahmad, Catherine D Ahmed, Christie M Ballantyne, Seth J Baum, Mafalda Bourbon, Alain Carrié, Marina Cuchel, Sarah D de Ferranti, Joep C Defesche, Tomas Freiberger, Ray E Hershberger, G Kees Hovingh, Lala Karayan, Johannes Jacob Pieter Kastelein, Iris Kindt, Stacey R Lane, Sarah E Leigh, MacRae F Linton, Pedro Mata, William A Neal, Børge G Nordestgaard, Raul D Santos, Mariko Harada-Shiba, Eric J Sijbrands, Nathan O Stitziel, Shizuya Yamashita, Katherine A Wilemon, David H Ledbetter, Daniel J Rader, Convened by the Familial Hypercholesterolemia Foundation, Amy C Sturm, Joshua W Knowles, Samuel S Gidding, Zahid S Ahmad, Catherine D Ahmed, Christie M Ballantyne, Seth J Baum, Mafalda Bourbon, Alain Carrié, Marina Cuchel, Sarah D de Ferranti, Joep C Defesche, Tomas Freiberger, Ray E Hershberger, G Kees Hovingh, Lala Karayan, Johannes Jacob Pieter Kastelein, Iris Kindt, Stacey R Lane, Sarah E Leigh, MacRae F Linton, Pedro Mata, William A Neal, Børge G Nordestgaard, Raul D Santos, Mariko Harada-Shiba, Eric J Sijbrands, Nathan O Stitziel, Shizuya Yamashita, Katherine A Wilemon, David H Ledbetter, Daniel J Rader, Convened by the Familial Hypercholesterolemia Foundation
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.
Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Source: PubMed