Characterizing the Neurobehavioral Phenotype of Mendelian Disorders of Epigenetic Machinery

Mendelian disorders of the epigenetic machinery (MDEM) are a class of rare neurodevelopmental disorders caused by mutations or expression of epigenetic regulators – writers, erasers or readers of chromatin marks – that commonly result in intellectual disability or developmental delays. Disruption in epigenetic mechanisms leaves dynamic effects in multisystem development - from cellular to neurobehavioral functioning. Recent advances in genetic research have shown promising results with postnatal treatments in reversing defects in neurogenesis and cognitive functions in select MDEMs. To advance towards the development of epigenetic therapies, detailed characterization of cognitive and behavioural phenotypes of MDEMs is essential to identify outcome targets of clinical trials.

The goal of this Research Topic is to assemble a collection of complementary original research and systematic review articles on cognitive and/or behavioral phenotypes of individual MDEMs or cross-MDEMs to elucidate potential targets for therapeutic trials and inform clinical care practices in the long-term management of the disease. Integration of multidisciplinary approaches - including physiological, behavioral, cognitive and imaging studies – will be vital to determine the downstream effect of disrupted epigenetic machinery on neurodevelopment and brain functions. Given the rarity of MDEMs, research on the neurological and behavioral phenotypes are largely on case reports with emphasis on retrospective chart reviews or naturalistic history data. Here, we aim to curate articles that focus on prospective investigations to better define clinical profiles associated with rare conditions. We particularly welcome submissions that cross-compare MDEMs or with other genetic disorders with a more established neurobehavioral phenotype.

This Research Topic aims to bridge this gap in research by inviting manuscripts that emphasize defining the neurological and behaviour profiles of specific MDEMs individually or across syndromes by utilizing imaging, physiological, cognitive and/or behavioral research methods. It is expected that this volume will serve as the first collection of complementary studies that will offer insight into the overlapping neurologic and behavioural features across MDEMs with commonly affected epigenetic regulators or other genetic conditions, which in turn will aid in the identification of common pathophysiological mechanisms underlying the diseases and therapeutic targets.

Topic Editor Jacqueline Harris receives financial support from Oryzon Genomics, LTD and Topic Editor Angela Morgan receives financial support from REDENLAB. The other Topic Editors declare no competing interests with regard to the Research Topic subject.