title: Familial Hypercholesterolaemia in the Era of Genetic Testing.
abstract: Familial hypercholesterolaemia (FH) is a relatively common autosomal dominant genetic condition leading to premature ischaemic vascular disease and mortality if left untreated. Currently, a universal consensus on the diagnostic criteria of FH does not exist but the diagnosis of FH largely relies on the evaluation of low density lipoprotein-cholesterol (LDL-C) levels, a careful documentation of family history, and the identification of clinical features. Diagnosis based purely on lipid levels remains common but there are several limitations to this method of diagnosis both practically and in the proportion of false-negatives and false-positives detected, resulting in substantial under-diagnosis of FH. In some countries, diagnostic algorithms are supplemented with genetic testing of the index case as well as genetic and lipid testing of relatives of the index case. Such "cascade" screening of families following identification of index cases appears to not only improve the rate of diagnosis but is also cost-effective. Currently, we observe a great variation in the excess mortality among patients with FH, which likely reflects a combination of additional genetic and environmental effects on risk overlaid on the risk associated with FH. Current accepted drug therapies for FH include statins and PSCK9 inhibitors. Further work is required to evaluate the cardiovascular disease risk in patients with genetically diagnosed FH and to determine whether a risk-based approach to the treatment of FH is appropriate.
authors.affiliation: Department Metabolic Medicine/Chemical Pathology, Lister Hospital, Stevenage, SG1 4AB, UK.
authors.forename: D P
authors.initials: DP
authors.lastname: Hughes
authors.affiliation: Department Metabolic Medicine/Chemical Pathology, Lister Hospital, Stevenage, SG1 4AB, UK. adie.viljoen@nhs.net.
authors.forename: A
authors.initials: A
authors.lastname: Viljoen
authors.affiliation: Department Metabolic Medicine/Chemical Pathology, Guy's & St Thomas' Hospitals, St Thomas' Hospital, Lambeth Palace Road, London, SE1 7EH, UK.
authors.forename: A S
authors.initials: AS
authors.lastname: Wierzbicki
mesh_terms: D002318:Cardiovascular Diseases / Q000209:etiology / Q000235:genetics / Q000517:prevention & control; D008078:Cholesterol, LDL / Q000235:genetics; D003362:Cost-Benefit Analysis; D005820:Genetic Testing / Q000191:economics / Q000379:methods; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006938:Hyperlipoproteinemia Type II / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D008403:Mass Screening / Q000191:economics; D009154:Mutation / Q000235:genetics; D011973:Receptors, LDL / Q000235:genetics; D012307:Risk Factors
chemical_list: D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011973:Receptors, LDL
keywords: Diagnostic criteria; Familial hypercholesterolaemia; Genetic testing