[Pathophysiology of Rett syndrome from the standpoints of clinical characteristics and clinical neurophysiological findings].

The pathophysiology of Rett syndrome (RTT) was discussed by reviewing the characteristic clinical features and neurophysiological studies. The electroencephalography (EEG), sensory evoked potentials (SEP), sleep-wake rhythm (SWR) study and polysomnographical (PSG) study showed age dependent characteristics. The findings in EEG and SEP studies suggested the specific subcortical and cortical involvements taking place during the development. PSG suggested the early dysfunction of the brainstem and midbrain monoaminergic systems; hypoactive serotonin and noradrenaline systems and dopaminergic system associated with receptor supersensitivity. The monoaminergic systems are known to influence the maturation of the higher neuronal systems at specific areas and at the critical developmental stages. Particularly the synaptogenesis of the cerebral cortex are modulated by region or layer specifically from early stage of the development. The age dependent appearance of characteristic clinical features of RTT, and the variation of the clinical severities; e.g. classical, variant, form fruste etc. can be explained by the specific features of these monoaminergic systems. The analysis of the components of rapid eye movement sleep (REM) suggested the onset of RTT lies between 36 gestational weeks to 3-4 months postnatally. The roles of the causative gene, methyl-CpG-binding protein 2 gene (MECP2) are thought to modulate the transcription of the specific target genes which act these area at specific developmental stages.