10 Disease penetrance in asymptomatic carriers of familial cardiomyopathy variants

• DOI: 10.1136/heartjnl-2022-bcs.10
• Publication Date: 2022-06-06T13:15:23Z
• Authors: Adil Mahmood; Deborah Morris-Ro...; Matthew Edwards; Andrew Fleming; Tessa Homfray; Samantha Mason; Ellie Quinn; James Ware; John Baksi; Sanjay Prasad; Antonis Pantazis; Brian Halliday
• Keywords: Penetrance; LMNA; Asymptomatic carrier; Restrictive cardiomyopathy

<h3>Introduction</h3> Predictive genetic testing allows the identification of at-risk first-degree relatives patients with cardiomyopathies. Data on penetrance variants associated cardiomyopathies is limited. The aim this study was to investigate disease in asymptomatic carriers familial cardiomyopathy hypertrophic (HCM), dilated (DCM) and arrhythmogenic right ventricular (ARVC). <h3>Methods</h3> We included individuals referred Royal Brompton Hospital for predictive after finding a pathogenic or likely variant relative between January 2017 December 2019. Cardiomyopathy diagnosis defined by international guidelines. Those prior signs symptoms heart at time were excluded.Results:A total 105 genotype-positive from 80 families evaluated (median age 24.9 years [interquartile range: 16.1 45.0 years], 51 [48.6%] males). Variants genes DCM included: TTN n = 16 (51.6%), MYH7 5 (16.1%), LMNA 3 (9.7%), TNNI3 RBM20 2 (6.5%), BAG3 1 (3.2%), DMD (3.2%); HCM MYBPC3 31 (47.7%), 25 (38.5%), TPM1 (7.7%), PLN (1.5%), TNNC1 TNNT2 (1.5%); ARVC PKP2 4 (44.4%), DSP FLNC (11.1%). On first clinical evaluation diagnosed DCM, hypokinetic non-dilated (HNDC) isolated left (LV) dilatation; 10 65 HCM; 0 9 ARVC. Over median follow-up 2.4 (interquartile 1.0 4.3 years) an additional 13 84 developed phenotypes (0 20 HNDC, LV dilatation, 7 55 HCM, ARVC). Furthermore, DCM/HCM received implantable cardioverter defibrillators loop recorders. <h3>Conclusions</h3> Approximately one-third phenotype initial screen during short period. This confirms importance need genotype-positive, phenotype-negative individuals. <h3>Conflict Interest</h3> None