Documents & Announcements

Clinical Genetic Testing for Familial Hypercholesterolemia

Amy C.Sturm MS, Joshua W.Knowles MD, PhD, Samuel S.Gidding MD, Zahid S. Ahmad MD, Catherine D. Ahmed MBA, Christie M. Ballantyne MD, Seth J. Baum MD, Mafalda Bourbon PhD, Alain Carrié MD, PhD, Marina Cuchel MD, PhD, Sarah D. de Ferranti MD, MPH, Joep C. Defesche PhD, Tomas Freiberger MD, PhD, Ray E. Hershberger MD, G. Kees Hovingh MD, PhD, Lala Karayan MPH, Johannes Jacob Pieter Kastelein MD, PhD, Iris Kindt MD, MPH, Stacey R. Lane JD, MBE, Sarah E. Leigh MSc, PhD, MacRae F. Linton MD, Pedro Mata MD, PhD, William A. Neal MD, Børge G. Nordestgaard MD, DMSc, Raul D. Santos MD, PhD, Mariko Harada-Shiba MD, PhD, Eric J. Sijbrands MD, PhD, Nathan O. Stitziel MD, PhD, Shizuya Yamashita MD, PhD, Katherine A. Wilemon BSc, David H.Ledbetter PhD, Daniel J.Rader MD, Convened by the Familial Hypercholesterolemia Foundation

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.