Prenatal testing for imprinting disorders: A laboratory perspective

Abstract

AbstractImprinting Disorders (ImpDis) are a group of congenital syndromes associated with up to four different types of molecular disturbances affecting the monoallelic and parent‐of‐origin specific expression of genomically imprinted genes. Though each ImpDis is characterized by aberrations at a distinct genetic site and a specific set of postnatal clinical signs, there is a broad overlap between several of them. In particular, the prenatal features of ImpDis are non‐specific. Therefore, the decision on the appropriate molecular testing strategy is difficult. A further molecular characteristic of ImpDis is (epi)genetic mosaicism, which makes prenatal testing for ImpDis challenging. Accordingly, sampling and diagnostic workup has to consider the methodological limitations. Furthermore, the prediction of the clinical outcome of a pregnancy can be difficult. False‐negative results can occur, and therefore fetal imaging should be the diagnostic tool on which decisions on the management of the pregnancy should be based. In summary, the decision for molecular prenatal testing for ImpDis should be based on close exchanges between clinicians, geneticists, and the families before the initiation of the test. These discussions should weigh the chances and challenges of the prenatal test, with focus on the need of the family.