SHANK3 and Rett syndrome: Following promising preclinical studies demonstrating that viral-mediated gene replacement in postnatal animals improves brain and behavioral phenotypes (15, 16), clinical trials are underway for the replacement of the methyl-CpG binding protein 2 (MECP2) gene in Rett syndrome and the SH3 and multiple ankyrin repeat domains 3 (SHANK3) gene in Phelan-McDermid syndrome.