Extensive information on the spectrum of clinical features and disease progression in RTT has been acquired from the US Natural History Study (NHS) of RTT and Related Disorders, which enrolled people with RTT and disorders with clinical and genetic relationships to RTT: MECP2 Duplication Syndrome (MDS); CDKL5 Deficiency Disorder (CDD); and FOXG1 Syndrome (FS). Here, MECP2 is linked to Down syndrome.