Abstract 12832: Yield From Family Screening in a National Adolescent Cardiac Screening Program

Abstract

Introduction: Cascade family screening in inherited heart disease is often reserved for probands with a clinical diagnosis. This study assessed the yield of family screening in a national cardiac screening program, comparing a clinical and a clinical/genetic screening algorithm. Methods: 2708 teens (14-16 years) participated in a national cardiac screening program. Probands with suspected or confirmed inherited cardiac disease were evaluated clinically and genetically (216 cardiac gene panel). Relatives were subjected to a standard clinical screening protocol. Segregation analysis (Sanger sequencing) was performed in families with gene positive (G+) probands (VUS, likely or definite pathogenic mutations as per ACMJ criteria). Cascade screening was limited to a) first degree relatives and/or b) G+ individuals in the presence or absence (not exceeding two generations) of a clinical phenotype. A standard clinical algorithm (family screening in probands with a pre-clinical or clinical diagnosis) was compared with a genetic lead algorithm. Results: 2(0.1%) probands were diagnosed with a cardiac phenotype (n=1 HCM, n=1 LQTS). Another 17(0.6%) probands had evidence of pre-clinical disease. 81 relatives (60.5% female) underwent evaluation, mean age 41.1±16.7 at first evaluation. 11 families (57.9%) were G+. 54(66.7%) were first degree relatives. 12(14.2%) were screened because of a phenotype in the proband, 57(70.4%) because of a pre-clinical ECG. Another 12(14.8%) were screened because of the family genotype, translating into a 7.4% higher referral rate. The diagnostic yield was higher in the presence of a proband phenotype (41.7% vs 4.3%, p=0.001). Using a standard clinical algorithm, the diagnostic yield of family screening was 10.1% (n=2 HCM, n=5 LQTS). Adding genetics to the algorithm identified another individual (n=1 DCM), equating to a mildly decreased overall yield of 9.9%. The yield between both algorithms was not significantly different (p=0.956). Conclusion: The yield of family screening in probands with a pre-clinical phenotype or clinical diagnosis was 10.1%. This was similar (9.9%) when incorporating genetic testing in the algorithm. The added benefit of systematic genetic testing in a family screening program is limited.