Key result
Systematic genetic screening identifies pathogenic variants in ~40% of adults with HCM.
Why the study?
Systematic genetic screening for hypertrophic cardiomyopathy is recommended, but the optimal screening approach remains debated.
Does systematic genetic screening identify pathogenic variants in adults with hypertrophic cardiomyopathy?
Observational (n=748)
Yes
Does systematic genetic screening identify pathogenic variants in adults with hypertrophic cardiomyopathy?
Systematic genetic screening in adults with hypertrophic cardiomyopathy yields a genetic diagnosis in nearly 40% of patients, with higher success rates in younger patients and those with a family history.
BACKGROUND: Although the optimal approach is debated, systematic genetic screening for hypertrophic cardiomyopathy (HCM) is recommended. AIMS: The performance of this approach was tested in GEREMY, a HCM prospective observational French register. METHODS: Screening was based on a 12-gene panel, including the Fabry disease (GLA) and the transthyretin (TTR) genes. In case of a negative result and according to the clinical profile, 17-80 gene panels of were used. RESULTS: A 748 adult cohort was examined: 68.9 % male, 54.6 ± 18.1 years, 27.5 % with a HCM family history, maximal wall thickness 19.1 ± 4.8 mm. Pathogenic or likely pathogenic variants were identified in 296 (39.6 %) patients, localized 1) in sarcomeric genes in 233, most frequently MYBPC3 (150) and MYH7 (42), with 24 identified only by large panels, with multiple variants in 8 patients and 2) in non-sarcomeric genes in 63, identified only with large panels in 26, predominantly TTR (26) and GLA(9), representing 8.8 % and 3.0 % of positive studies, respectively. Performance was 57.1 % before 40 years and 68.6 % in case of FH (vs otherwise 28.7 % and 26.1 % respectively, p < 0.001). In patients with a negative study, 148 had variants of unknown significance and 95 had senile or AL amyloidosis. CONCLUSIONS: Systematic genetic screening with a limited panel showed good performance, with diagnosis of Fabry disease (∼1 %) and hereditary TTR amyloidosis (∼3.5 %). Larger targeted panels were conclusive in 35.3 % of patients, of which 12 % had a negative initial approach.
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Hagège et al. (2024) conducted an observational in Hypertrophic cardiomyopathy (HCM) (n=748). Systematic genetic screening was evaluated on Identification of pathogenic or likely pathogenic variants. Systematic genetic screening identified pathogenic or likely pathogenic variants in 39.6% of adults with hypertrophic cardiomyopathy, including diagnoses of Fabry disease and hereditary TTR amyloidosis.
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