Table 2.

Clinical and Electrophysiological Stages of Rett Syndrome Natural Progression.^a

Rett syndrome stage	Age	Clinical characteristics	EEG findings
1. Early onset stagnation stage	6 mo to 2 y	Developmental arrest Changed communication and personality Diminished play interest Hand washing stereotypy Decelerating head growth	Normal If abnormal: mild background slowing, spike wave discharge in sleep
2. Rapid destructive stage	2 to 4.5 y	Developmental regression with autistic traits and dementia Apraxic/ataxic gait Loss of hand skills Onset of seizures and hyperventilation	Normal to mild background slowing Centrotemporal spike or sharp waves Poorly formed sleep (loss of non-REM) Atypical spike and wave discharges enhanced by sleep
3. Pseudostationary/plateau stage	2 y to adulthoodSome patients remain in stage 3 for their entire lives	Increased attentiveness and decreased autistic traits Intellectual disability Gross motor dysfunction and apraxia Seizures	Poorly formed posterior dominant rhythm Low-voltage, poorly reactive, generalized slowing Poorly formed sleep architecture (absent non-REM) High-voltage delta and spike wave in sleep Multifocal spike wave and rhythmic bursts of central delta activity
4. Late motor deterioration stage	>10 y	Decrease or loss of mobility Decreasing seizures Growth retardation and weight loss	Marked background slowing with fronto-central rhythmic delta Multifocal spike wave Generalized slow spike wave in sleep Epileptiform activity may be absent

Abbreviations: EEG, electroencephalography; REM, rapid eye movement.

^a Rett syndrome progresses from stage 1 where patients have a stagnation of developmental gains and normal to mildly slow background on EEG to a period of rapid developmental regression with increasingly abnormal EEG findings, and finally a plateau phase with stable developmental disability and signs of encephalopathy on EEG. Some patients progress to further motor deterioration and decreasing seizure burden with reduced epileptiform activity on EEG.