Epigenetic Developmental Disorders: CHARGE syndrome, a case study.

Epigenetic events including chromatin remodeling and histone modifications have recently emerged as important contributors to a variety of neurodevelopmental disorders. This review focuses on CHARGE syndrome, a multiple anomaly condition caused by mutations in the gene encoding CHD7, an ATP-dependent chromatin remodeling protein. CHD7 exhibits pleiotropic effects during embryonic development, consistent with highly variable clinical features in CHARGE syndrome. In this review, a historical description of CHARGE is provided, followed by establishment of diagnostic criteria, gene discovery, and development of animal models. Current understanding of epigenetic CHD7 functions and interacting proteins in cells and tissues is also presented, and final emphasis is placed on challenges and major questions to be answered with ongoing research efforts.