Paediatric evaluation for inherited conditions: how do we investigate?

The importance of cardiological evaluation of families following sudden unexplained death (SUD) or diagnosis of an inherited cardiac condition (ICC) has been long established. 3 The additional value of genetic testing, in the context of a likely ICC, is also recognized. Tomaske et al. report on their experience of paediatric investigation for ICCs. Their study cohort consists of a heterogeneous population referred consecutively to a tertiary centre over a 5-year period. Paediatric blood relatives with known familial ICC or SUD were included. The authors devised an investigational protocol, with an electrocardiogram (ECG), 24 h Holter monitoring, and echocardiogram in the first instance, followed by signal-averaged ECG, an event recorder, and cardiac magnetic resonance imaging as required. Mutation analysis followed upon the demonstration of a cardiac channelopathy phenotype. This offers an opportunity to compare diagnostic yields in evaluation focused on paediatric subjects with that of previously reported predominantly adult groups. A disease prevalence of 39% was demonstrated among children in whose families an ICC was already confirmed, providing a compelling argument for the investigation of these children, even when asymptomatic. This reflects the autosomal dominant inheritance of the ICCs encountered, diluted by the investigation of non-first-degree relatives referred due to anxiety in a family. Hence, in affected families, where disease-causing mutations are not identified and cannot guide their assessment, it is incumbent upon physicians to offer cardiological evaluation of children. Among SUD families, where investigation of adult relatives was non-diagnostic or where no adult relatives were referred for evaluation, paediatric cardiological evaluation is supported by a diagnostic yield of 20%. This compares favourably with existing data in families with predominantly adult members and supports the evaluation of children, even when the index case’s first presenting symptom was sudden death in adulthood. Sudden death risk in paediatric relatives