Figure 1.
Impact of extended testing on clinical management of patients with IPDs. Once IPDs are ruled out, which may require stem cell transplantation or substitution of defect thrombopoietin, extended diagnosis of IPDs is primarily relevant for patients with MYH9 disorders. In these patients, inhibition of the renin-angiotensin pathway in case of proteinuria can prevent progression to renal failure. In all other IPDs, extended testing has no major impact on management. However, for some patients, it might be a relief of disease burden to know the reason for the bleeding tendency, but identifying the reason is often more important for concomitant disease manifestations in syndromic forms. Documentation of the specific diagnosis may also help to avoid later mistreatment as immune thrombocytopenia. It is important to be aware of the risk of causing additional severe disease burden when extended testing (either by NGS or other methods like immunofluorescence) reveals gene mutations with an increased risk for leukemia or other pathologic variants as incidental findings. At the least, specific informed consent should be obtained before testing for gene mutations with an increased risk for malignancies (RUNX1, ANKRD26, ETV6) and for reporting of incidental findings. Patients have the right to “not know.” This could be respected by creating virtual gene panels, allowing patients/parents an opt-out decision. The informed consent procedure before extended testing for IPDs, especially using NGS, should be very specific on why tests are performed, which results may be obtained, including the consequences they may have, and whether the patient wants to know results that have no direct relevance for management and/or treatment. CAMT, congenital amegakaryocytic thrombocytopenia; HPS, Hermansky-Pudlak syndrome; ITP, immune thrombocytopenia; MECOM, congenital amegakaryocytic thrombocytopenia and radioulnar synostosis; THPO, thrombopoietin mutation; WAS, Wiskott-Aldrich syndrome; WES, whole-exome sequencing.