One in five relatives of ECG-positive phenotype-negative adolescents received a cardiomyopathy diagnosis or had early cardiomyopathy traits, and a joint clinical-genetic approach may aid early detection in selected families, though findings remain exploratory and require validation in larger cohorts.
Only a small proportion of adolescents screened nationally met criteria as ECG-positive phenotype-negative, and a minority of these carried a pathogenic cardiomyopathy variant.
About one in five relatives of these adolescents were referred after clinical screening, mostly because of an abnormal ECG.
Early cardiomyopathy traits were present at baseline in a sizeable proportion of relatives.
Cardiomyopathy was newly diagnosed in a few relatives at baseline.
Cascade genetic testing identified one gene-positive/phenotype-negative relative.
One relative with early traits phenoconverted during follow-up, bringing the overall diagnostic rate to 5.6%.
A joint clinical-genetic approach enabled personalized surveillance for some relatives and identified diagnoses that conventional clinical screening alone would have missed.
The authors conclude that extending family screening to relatives of ECG-positive phenotype-negative adolescents is justified, while noting findings are exploratory.
Some teenagers have an abnormal heart tracing (ECG) on screening even though detailed tests show no heart muscle disease. This study asked whether it is worthwhile to test their family members, and whether adding genetic testing to the usual heart checks helps. Out of a nationwide screening program, only 16 adolescents (0.6%) fit this description, and 3 of them carried a disease-causing gene variant linked to heart muscle disease. Among 71 relatives, about 1 in 5 had either a new heart muscle disease diagnosis or early signs of one. Three relatives (4.2%) were diagnosed at the start, and one more developed a condition years later (at 77 months), for an overall diagnosis rate of 5.6%. Combining genetic and clinical evaluation allowed tailored follow-up for 6 relatives and uncovered 2 diagnoses that standard clinical screening alone would likely have missed. This research suggests that checking relatives of such adolescents may help find heart muscle disease early in some families. However, the study was small, involving few families, so the authors describe the results as exploratory and say larger studies are needed to confirm them.
Abela M, Debattista J, Scerri J, Felice T, Grech V, Scerri C. (2026). Family screening for genetic cardiomyopathies in ECG-positive phenotype-negative adolescents: a joint clinical and genetic approach.. European journal of pediatrics. https://doi.org/10.1007/s00431-026-07524-y