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Clinical epigenetics: a primer for the practitioner

Disruption of epigenetic modifications and the factors that maintain these modifications is rapidly emerging as a cause of developmental disorders. Here we summarize some of the major principles of epigenetics including how epigenetic modifications are: (1) normally reset in the germ line, (2) form an additional layer of interindividual variation, (3) are environmentally sensitive, and (4) change over time in humans. We also briefly discuss the disruption of growth and intellect associated with the Mendelian disorders of the epigenetic machinery and the classical imprinting disorders (such as Beckwith–Wiedemann syndrome, Silver–Russell syndrome, Prader–Willi syndrome, and Angelman syndrome), as well as suggesting some diagnostic considerations for the clinicians taking care of these patients. Finally, we discuss novel therapeutic strategies targeting epigenetic modifications, which may offer a safe alternative to up and coming genome editing strategies for the treatment of genetic diseases. This review provides a starting point for clinicians interested in epigenetics and the role epigenetic disruption plays in human disease.