Effectiveness of alternative strategies to define index case phenotypes to aid genetic diagnosis of familial hypercholesterolaemia

Abstract

Patients with tendon xanthoma (definite FH) should be genotyped. In patients with possible FH, the presence of a personal history of CHD or imaging evidence of increased atheroma offers the best method of identifying index patients likely to have monogenic FH.

The Agenda for Familial Hypercholesterolemia

“…88 An observational study suggests that imaging may improve clinical differentiation between patients with heterozygous FH and those with polygenic or secondary hypercholesterolemia. 89 Despite the evidence that subclinical atherosclerosis is more frequent and more intense in individuals with heterozygous FH than in matched normolipidemic subjects, there is to date no FH-specific evidence that the detection of advanced subclinical disease will improve reclassification of cardiovascular risk. [80][81][82][83] Childhood may be particularly important because risk may be underestimated in this age group.…”

Integrated guidance on the care of familial hypercholesterolaemia from the International FH Foundation

“…However, failure to detect a mutation does not exclude a diagnosis of FH, particularly if the clinical phenotype is highly suggestive of FH [6,8]. To optimize the use of resources, DNA testing may only be offered to index patients with DLCNS >5 or meeting the Simon Broome possible criteria, especially those with a personal history of early onset (<60 years) CVD or imaging evidence of significant subclinical atherosclerosis [8,57,[84][85][86].…”

Characteristics and Vascular Complications of Familial Hypercholesterolemia in Korea

“…In addition, information regarding genetic characteristics as 20% (Table 1). Although the incidence of xanthoma varies with inclusion criteria, the incidence in Korean patients is lower than that in patients from the UK 16) , Hong Kong 13) , and Japan 11) (47%, 50%, and 87%, respectively).…”