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

Abstract

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, 46 second‐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.

A cross-national investigation of cardiovascular survival in homozygous familial hypercholesterolemia: The Sino-Roman Study

“…48 We classified genetic mutations according to the methodology used in previous research. 14,49 Studies in hoFH from the United States, 50 Spain, 51 and France 14 have demonstrated that patients with receptor negativemutations exhibit earlier onset of CVD and reduced survival compared with those with receptor defective mutations; our results accord with this ( Fig. 3).…”

A Global Review on the Utility of Genetic Testing for Familial Hypercholesterolemia

“…Cascade screening was performed in 12 of the 21 studies, which occurred in Italy, Spain, Slovak Republic, India, Estonia, China, Vietnam, and Western Australia [28][29][30][31][32][33][34][35][36][37][38][39]. Among those 12 studies, the evidence suggested that first-degree relatives showed improved FH diagnosis and underwent treatment initiation, continued treatment, and/or treatment modification that resulted in improved LDL and total blood cholesterol.…”

“…Finally, more research is needed to examine and determine the role of non-clinical outcomes and PROs following FH genetic testing, identify resources needed to inform treatment goals and help improve treatment outcomes in FH patients, and assess clinical outcomes following FH genetic testing in non-Caucasian and pediatric populations in the US and abroad. [38] China [30] Setia et al [32] Pang et al [28] Abul-Husn et al [21] Jones et al [27] Wang et al [63] Wu et al [33] Truong et al [34] Rubio-Marín et al [36] Alver et al [39] Continued treatment 92.26…”

“…Sperlongano et al [30] Pang et al [28] Abul-Husn et al [21] Jones et al [27] Wang et al [63] Rubio-Marín et al [36] Improved total blood cholesterol levels 0.01 Sperlongano et al [30] Vohnout et al [29] Setia et al [32] Pang et al [28] Averna et al [60] Wu et al [33] Rubio-Marín et al [36] Alver et al [39] Genetic counseling 5. 63 Averna et al [60] Jones et al [27] None reported 86.…”

“…63 Averna et al [60] Jones et al [27] None reported 86. 33 Sperlongano et al [30] Amor-Salamanca et al [31] Minicocci et al [61] Séguro et al [62] Abul-Husn et al [21] Wang et al [63] Truong et al [34] Tan et al [35] Gómez et al [64] Cui et al [42] Ibarretxe et al [37] Chan et al [38] Cao et al [65]…”