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.
Subject(s)
Expert Testimony/methods , Genetic Counseling/methods , Genetic Testing/methods , Hyperlipoproteinemia Type II/diagnosis , Hyperlipoproteinemia Type II/genetics , Apolipoproteins B/blood , Apolipoproteins B/genetics , Expert Testimony/standards , Genetic Counseling/standards , Genetic Testing/standards , Humans , Hyperlipoproteinemia Type II/blood , Proprotein Convertase 9/blood , Proprotein Convertase 9/genetics , Receptors, LDL/blood , Receptors, LDL/geneticsABSTRACT
PURPOSE OF REVIEW: In this review, we examine benefits and concerns associated with genetic testing in the clinical management of familial hypercholesterolemia (FH). RECENT FINDINGS: Application of next-generation sequencing and other advances provide improved yield of causal mutations compared with older methods and help disclose underlying pathophysiology in many instances. Concerns regarding clinical application of genetic testing remain. SUMMARY: More widespread application of genetic testing for FH in the USA may be forthcoming. When a genetic cause of FH can be identified or is known for the family, test results can provide more accurate individual diagnosis of FH, clarification of underlying pathophysiology, and greater clinical insight. However, several concerns persist, particularly cost to FH patients, potential discrimination, and inappropriate denial of clinically indicated therapies for patients without definitive genetic testing results.
