Abstract
PURPOSE: We compared new cases detected per index case in familial hypercholesterolemia (FH) families with or without an identifiable monogenic etiology. METHODS: We enrolled 52 FH probands with a pathogenic variant (FH(g+)) in LDLR, APOB, or PCSK9 and 73 probands without such a variant (FH(g-)). After direct contact by the study team, family members (FMs) of FH(g+) probands could opt-in for genetic testing and FMs of FH(g-) probands were asked to provide a lipid profile. New cases were defined as presence of a pathogenic variant in FH(g+) families and as low-density lipoprotein cholesterol ≥155 mg/dL in FH(g-) families. RESULTS: Of 71 FH(g+) probands seen by a genetic counselor, 52 consented and identified 253 FMs (111 consented and were tested, yielding 48 new cases). Of 101 FH(g-) probands who received counseling, 73 consented and identified 295 FMs (63 consented and were tested, yielding 17 new cases). New case detection per index case was significantly greater in FH(g+) than in FH(g-) families (0.92 vs 0.23), a result of higher cascade testing uptake (43.9 vs 21.4%) and yield (43.2 vs 27.0%) in the former. CONCLUSION: New case detection rate was significantly higher in FH families with a monogenic etiology than in those without such an etiology owing to greater uptake and yield of cascade testing.