Clinical spectrum and management of imprinting disorders

Medizinische Genetik, vol. 32, pp. 321–334

Abstract

Abstract Imprinting disorders are exceptional within the group of monogenic syndromes. They are associated with molecular changes affecting imprinted regions and usually do not follow the rules of Mendelian inheritance. They account for a relevant proportion of congenital disorders, especially within the syndromal growth entities with endocrine, neurological, and skeletal characteristics. In patients with imprinting disorders and accelerated growth, significant tumor risks have to be considered. The number of known imprinting disorders increases with the identification of new regions in which parentally imprinted genes are located. Imprinting disorders are caused by genomic pathogenic variants affecting imprinted genes, as well as by aberrant imprinting marks (epimutations) in the patients themselves. Additionally, maternal effect mutations have recently been identified that trigger secondary epimutations in the offspring. These maternal effect mutations explain not only imprinting disorders in their children, but also recurrent reproductive failure in the families. This review aims to provide an overview of the recent findings in 13 well-known imprinting disorders relating to clinical diagnosis, management and counseling.

Authors 6

1. Miriam Elbracht corresponding Aachen Medical Faculty Institute of Human Genetics

   RWTH Aachen University

   Affiliation as printed

   Institute of Human Genetics, Medical Faculty , RWTH Aachen University , Pauwelsstr. 30 , Aachen , Germany

   Institute of Human Genetics, Medical Faculty, RWTH Aachen University, Pauwelsstr. 30, D-52074Aachen, Germany

2. Gerhard Binder

   University of Tübingen · Universitätsklinikum Tübingen · University Children's Hospital Tübingen

   Affiliation as printed

   Pädiatrische Endokrinologie, Universitätsklinik für Kinder- und Jugendmedizin , Universitätsklinikum Tübingen , Tübingen , Germany

3. Olaf Hiort

   University of Lübeck

   Affiliation as printed

   Department of Paediatrics and Adolescent Medicine, Division of Paediatric Endocrinology and Diabetes , University of Lübeck , Lübeck , Germany

4. Cordula Kiewert
   Affiliation as printed

   Pediatric Endocrinology and Diabetology , Children’s University Hospital Essen , Essen , Germany

5. Christian Peter Kratz

   Medizinische Hochschule Hannover

   Affiliation as printed

   Department of Pediatric Hematology and Oncology , Hannover Medical School , Hannover , Germany

6. Thomas Eggermann Aachen Medical Faculty Institute of Human Genetics

   RWTH Aachen University

   Affiliation as printed

   Institute of Human Genetics, Medical Faculty , RWTH Aachen University , Pauwelsstr. 30 , Aachen , Germany

   Institute of Human Genetics, Medical Faculty, RWTH Aachen University, Pauwelsstr. 30, D-52074Aachen, Germany