Imprinting disorders: novel findings and translation into diagnostics and management

Imprinting disorders (ImpDis) are a group of human congenital diseases involving one or more genes that are expressed from only the paternal or the maternal allele.Currently ∼100 imprinted human genes and twelve imprinting disorders have been recognized.From a clinical point of view, imprinting disorders are a heterogeneous group of diseases, which mainly affect growth, neurodevelopment and metabolism, but there is a considerable phenotypic overlap between some disorders (e. g. the Prader-Willi, Temple and Schaaf-Yang syndromes).Though each ImpDis is rare, they altogether affect approximately 7,500-10,000 patients in the European Union.Furthermore, it is likely that ImpDis are much more common than realised and therefore there is an increasing demand for ImpDis testing.The reasons for this underestimation are diverse, ranging from clinical heterogeneity, non-specificity of key features, clinical as well as molecular overlaps, to (epi)genetic mosaicism as a diagnostic challenge.Though many of these limitations are far from being overcome, there is a remarkable progress in diagnosing ImpDis.The recent identification of new molecular disturbances, the implementation of comprehensive molecular and clinical diagnostic tools, and novel approaches towards causal therapies already contribute to a more directed management of the patients and their families.In this issue, we highlight novel insights into mechanisms of genomic imprinting and epigenetic regulation, which have been obtained in the last years.Prawitt and Haaf not only review the basic mechanisms of imprinting and the major types of molecular alterations, but they also refer to recently identified trans-acting factors causing aberrant imprinting marks.These fetal and maternal factors with an impact on early embryonic development are currently in the focus of research, but first results from