Reverse cascade screening for familial hypercholesterolemia in high-risk Chinese families

Background: Reverse cascade screening is not commonly employed to detect new cases of familial hypercholesterolemia (FH). We aimed to assess the outcome of this screening strategy in families in which the probands were children with severe FH. Hypothesis: Reverse cascade screening is an effective method to detect new patients with FH. Methods: Reverse cascade screening was undertaken starting from 47 index children with severe hypercholesterolemia; 39 were homozygous/compound heterozygous FH and 8 were heterozygous FH. Available parents, siblings, and second-degree relatives were contacted and screened. Results: From the 39 cases of homozygous/compound heterozygous FH, 80 first-degree family members were available for screening; 70 were parents and 10 were siblings. All first-degree relatives screened were genetically diagnosed with FH. None of the parents had been treated with statins at the time of diagnosis, and 10 (12.7%) had premature coronary artery disease. Additionally, 46second-degree relatives were screened, of which 41 (89%) were diagnosed with FH. From the 8 heterozygous FH children, 17 first- and second-degree relatives were screened and 12 new cases of FH were also diagnosed. Hence, the overall diagnostic yield of screening was 2.8 new cases of FH per index case. Conclusions: Reverse cascade screening is a highly effective method for diagnosing new cases of FH in parents, siblings, and second-degree relatives of index children with severe FH.