FIGURE 1.

Proposed workflow of a genome-wide next-generation sequencing-based screen of patients with pheochromocytoma or paraganglioma. (a) Initial steps of the screening process involve genetic counseling and informed consent (^apatient must opt in or out of ‘incidental finding’ reporting and decisions of future evaluation of the collected sequence data for future updates – see text for additional details). ^bIt is suggested that the final report be the consensus interpretation of physicians, researchers and clinical geneticists. (b) Results are returned to the patient at a genetic counseling session. Unquestionably, positive results follow the current route of clinical follow-up for index patient and screening of at-risk relatives. Negative results may include lack of a clearly pathogenic mutation in a known susceptibility gene or detection of variants of unknown significance (VUS). Regular updates on the status of VUS or evaluation of novel susceptibility genes from collected data are performed. If a new pathogenic variant is detected or pathogenic status of VUS is established, based on new research data, the patient will be offered genetic counseling and follow procedures for a ‘positive’ mutation carrier. If there are no changes in the genetic screening status, the process of regular updates may continue.