Imprinting disorders (ImpDis) are congenital conditions that are characterized by disturbances of genomic imprinting. The most common individual ImpDis are Prader-Willi syndrome, Angelman syndrome and Beckwith-Wiedemann syndrome. Individual ImpDis have similar clinical features, such as growth disturbances and developmental delay, but the disorders are heterogeneous and the key clinical manifestations are often non-specific, rendering diagnosis difficult. Four types of genomic and imprinting defect (ImpDef) affecting differentially methylated regions (DMRs) can cause ImpDis. These defects affect the monoallelic and parent-of-origin-specific expression of imprinted genes. The regulation within DMRs as well as their functional consequences are mainly unknown, but functional cross-talk between imprinted genes and functional pathways has been identified, giving insight into the pathophysiology of ImpDefs. Treatment of ImpDis is symptomatic. Targeted therapies are lacking owing to the rarity of these disorders; however, personalized treatments are in development. Understanding the underlying mechanisms of ImpDis, and improving diagnosis and treatment of these disorders, requires a multidisciplinary approach with input from patient representatives.
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