RESUMO
Imprinting Disorders are a group of rare diseases with overlapping phenotypes which are associated with similar molecular changes and affect imprinted chromosomal regions. Clinical features mainly occur prenatally or in childhood, but have a severe lifelong impact on health. Due to their clinical and molecular heterogeneity, the diagnosis of imprinting disorders is often challenging and requires testing of a broad spectrum of genomic variants and aberrant methylation of imprinted loci (epimutations). A significant number of patients suspicious for imprinting disorders remain without a molecular confirmation, and in these cases differential diagnoses have to be considered. In fact, in patients with clinical features suggestive for imprinting disorders, the precise identification of the molecular cause is relevant for both clinical management as well as for genetic counselling. Thus, a comprehensive testing approach has to be applied. Next generation sequencing (NGS) based studies show that this technique is a valuable tool to improve the diagnostic efficiency particularly in entities with broad differential diagnoses. Furthermore, the development of diverse NGS approaches allows new insights in the function of imprinted regions, their structures, interactions and regulation. Based on a large cohort of patients referred for routine Silver Russel syndrome testing, the appropriateness and limitations of first trial tests in imprinting disorders are demonstrated in this report, but the chances of genomic NGS approaches for diagnostics and research are elucidated as well. Finally, the significance of the precise molecular diagnosis for the personalized management of the patient, and genetic counselling of the family will be discussed.