Table 3 Considerations for return of incidental genetic findings to pediatric patients

Indication for testing

Differentiating incidental and primary findings can be difficult in some patients, especially when patients are very young and the age of onset associated with the finding is highly variable. Some identified findings thought to be incidental may represent variation that is associated with the indication for testing and reflects phenotypic expansion or symptom onset that is earlier than previously reported.

Family history

Although the pediatric patient is not exhibiting disease features associated with an incidental finding at time of testing, understanding family history may help determine variant relevance and utility of result return.

Age of onset

Age of disease onset is important to consider in the context of incidental findings. Variants associated with early-onset disease are more likely to alter patient outcome and may be more relevant to younger patients compared to those associated with later-onset disease. Further, as an example, variation associated with disease onset in infancy identified in an adolescent patient may represent variation that is not disease causal or disease with low penetrance.

Penetrance

Return of an incidental finding associated with completely penetrant disease is much more compelling than return of a finding that results in an associated phenotype in only a small proportion of individuals that harbor the genetic finding.

Clinical actionability

Clinical utility and actionability is important to consider in the context of incidental genetic findings. If the finding will alter patient care (e.g., management, treatment) in a way that is beneficial to outcome, then return of the result will be useful to the provider, patient, and family, and is warranted.

Personal utility

It is possible that patients and families receiving incidental genetic findings will find them to be of great personal utility. These types of findings may result in altruistic feelings, enhance self-knowledge and understanding, promote feelings of control, and allow for future planning.

Severity of disease

Incidental findings associated with severe disease phenotypes likely warrant more serious consideration for return. Knowledge about potential onset of severe disease will almost certainly be useful to the provider and patient/family in terms of planning, and may also improve both short and long-term outcomes.