Family screening of relatives of adolescents with abnormal ECGs but no clinical cardiomyopathy diagnosis resulted in an overall diagnostic yield of 5.6%.
Observational (n=2,672)
Yes
Does family screening identify cardiomyopathy in relatives of adolescent probands with abnormal ECGs but no clinical diagnosis?
Family screening in relatives of adolescents with abnormal ECGs but no clinical cardiomyopathy diagnosis yields a 5.6% diagnosis rate, suggesting potential benefit in expanding current screening criteria.
Abstract Introduction Cardiomyopathy typically presents in mid-adulthood, making diagnoses in adolescents uncommon. Current guidelines only recommend family screening when a proband is given a clincial diagnosis. This study evaluated the diagnostic yield of family screening in adolescents with abnormal ECG findings suggestive of cardiomyopathy, but without a clinical diagnosis. Methodology As part of a nationwide screening program (BEAT-IT), adolescents with pathological ECGs were referred for evaluation. These individuals underwent echocardiography, exercise testing, holter monitoring and cardiac MRI. Those without diagnostic imaging evidence of cardiomyopathy were recruited. A cardiac gene panel was also perfromed in these individuals, complented with genetic counselling by a multi-disciplinary team. Only likely or definite pathogenic (LP/P) variants (as per ACMG criteria) in cardiomyopathy genes were considered clincially relevant. Relatives were screened clinically with an ECG and echocaridography, offerring second line investigations if screening was abnormal. Cascade testing in families with a LP/P variant was also carried out in relatives. More indepth clinical phenotyping was offerred to gene positive (G+) relatives, even if ECG and echocaridography were normal. All G+ relatives were offerred surveillance. Results Of 2672 adolescents screened, 16 (0.6%) had abnormal ECGs without a cardiomyopathy diagnosis (T-wave inversion n=15, ST depression n=1). Three (18.8%) had LP/P variants in cardiomyopathy genes (MYH7, MYBPC3, ACTC1). 71 relatives were screened; 13 (18.3%) were referred, mostly for abnormal ECGs (n=9, 12.7%). Three (4.2%) received a diagnosis (HCM n=2, DCM n=1), and 10 (14.1%) remain under surveillance due to abnormal ECGs, non-diagnostic imaging, or LP/P variants (cardiomyopathy genes). At follow-up (59 ± 23 months), one additional relative was diagnosed with cardiomyopathy (NDLVC). This increased the overall diagnostic yield to 5.6%. Three of the four diagnosed relatives had LP/P variants. Genetic testing enabled more personalized surveillance in 8.4% of screened relatives. Conclusion Family screening identified cardiomyopathy or warranted surveillance in a fifth of relatives, demonstrating reasonable diagnostic yield in pre-clinical probands. Judicious use of genetic testing may support individualized screening strategies, though larger studies are needed to validate these findings.
Abela et al. (Mon,) conducted a observational in Cardiomyopathy (n=2,672). Family screening and genetic testing was evaluated on Overall diagnostic yield of cardiomyopathy in relatives. Family screening of relatives of adolescents with abnormal ECGs but no clinical cardiomyopathy diagnosis resulted in an overall diagnostic yield of 5.6%.
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