Prenatal testing for imprinting disorders: A laboratory perspective

Prenatal Diagnosis, vol. 43, pp. 973–982

Abstract

Imprinting 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.

Authors 7

1. Jasmin Beygo

   Essen University Hospital · University of Duisburg-Essen

   Affiliation as printed

   Institute of Human Genetics University Hospital Essen University of Duisburg‐Essen Essen Germany

   Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

   These authors contributed equally

2. Silvia Russo

   IRCCS Istituto Auxologico Italiano

   Affiliation as printed

   Medical Cytogenetics and Molecular Genetics Laboratory IRCCS Istituto Auxologico Italiano Milan Italy

   Medical Cytogenetics and Molecular Genetics Laboratory, IRCCS, Istituto Auxologico Italiano, Milan, Italy

   These authors contributed equally

3. Pierpaola Tannorella

   IRCCS Istituto Auxologico Italiano

   Affiliation as printed

   Medical Cytogenetics and Molecular Genetics Laboratory IRCCS Istituto Auxologico Italiano Milan Italy

   Medical Cytogenetics and Molecular Genetics Laboratory, IRCCS, Istituto Auxologico Italiano, Milan, Italy

4. Gijs W.E. Santen Aachen Department of Clinical Genetics Leiden University Medical Center Leiden The Netherlands Department of Clinical Genetics

   Leiden University Medical Center

   Affiliation as printed

   Department of Clinical Genetics Leiden University Medical Center Leiden The Netherlands

   Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands

5. Andreas Dufke

   University of Tübingen

   Affiliation as printed

   Institute for Medical Genetics and Applied Genomics Medical Faculty University of Tübingen Tübingen Germany

6. Elia Schlaich Aachen Institute for Human Genetics and Genome Medicine Medical Faculty Medical Faculty Institute for Human Genetics and Genome Medicine

   RWTH Aachen University

   Affiliation as printed

   Institute for Human Genetics and Genome Medicine Medical Faculty RWTH Aachen University Aachen Germany

   Medical Faculty, Institute for Human Genetics and Genome Medicine, RWTH Aachen University, Aachen, Germany

7. Thomas Eggermann corresponding Aachen Institute for Human Genetics and Genome Medicine Medical Faculty Medical Faculty Institute for Human Genetics and Genome Medicine

   RWTH Aachen University

   Affiliation as printed

   Institute for Human Genetics and Genome Medicine Medical Faculty RWTH Aachen University Aachen Germany

   Medical Faculty, Institute for Human Genetics and Genome Medicine, RWTH Aachen University, Aachen, Germany