In this study, we establish a connection between recent advances in CHD4 structure and function and 36 pathogenic <i>CHD4</i> mutations associated with rare diseases, including Sifrim-Hitz-Weiss syndrome, moyamoya angiopathy, and childhood idiopathic epilepsy with sinus arrhythmia, all of which exhibited cardiomyopathy, congenital heart defects, and/or vascular abnormalities. The gene discussed is CHD4; the disease is Sifrim-Hitz-Weiss syndrome.