H1-4 and overgrowth syndrome: As deregulated cellular growth is a hallmark of cancer, and certain human overgrowth syndromes are associated with increased cancer risk, it is not unexpected that the majority of the mutated genes in overgrowth syndromes including NSD1, EZH2, DNMT3A, PTEN, CHD8, HIST1H1E, MTOR, PIK3CA are also frequently altered in human cancers [51].