Clinical Genetic Testing for Familial Hypercholesterolemia

Although awareness of familial hypercholesterolemia (FH) increasing, this common, potentially fatal, treatable condition emains underdiagnosed, Despite FH being a genetic disorder, genetic testing is rarely used. The Familial. Hypercholeserolemia 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 (PCS10); other genes may also need to be considered for analysis based on patient phenotype. Expected outcomes nclude greater diagnoses, more effective cascade testing, initiation of therapies at earlier ages, and more accurate risk ratification. (C) 2018 by the American College of Cardiology Foundation,