Integration of child-parent screening and cascade testing for familial hypercholesterolaemia

Abstract

Objective: To integrate child-parent screening and cascade testing into a single pathway-child-parent cascade screening (CPCS), for the identification of familial hypercholesterolaemia in the population and to estimate the number of new familial hypercholesterolaemia cases identified per child screened and the associated costs.

Methods: We applied the results from the published MRC Child-Parent Screening Study to 10,000 children, together with cascade testing first degree relatives of parents with a familial hypercholesterolaemia mutation identified by child-parent screening. We estimated the number of familial hypercholesterolaemia cases identified per child screened, the median cost per familial hypercholesterolaemia case identified and the median cost per child screened to identify one case using a range of cholesterol and familial hypercholesterolaemia mutation testing costs. We present a case study to illustrate the application of CPCS in practice.

Results: CPCS identifies one new familial hypercholesterolaemia case per 70 children screened at a median estimated cost of £960 per new familial hypercholesterolaemia case or £4 per child screened. CPCS identifies an average of four new familial hypercholesterolaemia cases per family. In the case study, six new familial hypercholesterolaemia cases were identified, and preventive treatment started in five, with the index child expected to start when older.

Conclusion: CPCS for familial hypercholesterolaemia are complementary strategies. The sustainability of cascade testing relies on identifying new unrelated index cases. This is achieved with population-wide child-parent screening. Integrated CPCS is currently better than either method of familial hypercholesterolaemia detection alone. It has the potential to identify all, or nearly all, individuals with familial hypercholesterolaemia in the population at low cost.

Keywords: Familial hypercholesterolaemia; cascade; child–parent; screening.

Figure 1.

Integrated child–parent screening and cascade testing showing the number of tests (n) and FH-positive cases (FH+) identified based on screening 10,000 children. FH: familial hypercholesterolaemia.

Figure 2.

Case study of integrated child–parent screening and cascade testing. Ages to nearest year at time of testing FH positive. Total cholesterol (TC) and LDL-cholesterol (LDL) in mmol/L. All cases had the same FH mutation in LDLR gene (c.2093_2094dup). Medication started following identification is indicated.