Neurophysiology of Rett syndrome

Neurophysiological studies on Rett syndrome (RTT) are reviewed, and pathophysiology of RTT is discussed. The electroencephalography (EEG), sensory evoked potentials (SEP), sleep–wake rhythm study and polysomnography (PSG) study showed age-dependent characteristics. PSG revealed the brainstem and midbrain monoaminergic systems are deranged from early developmental stage, that is serotonin and noradrenaline systems seem to be hypoactive and dopaminergic system is also hypoactive associated with receptor supersensitivity. These monoaminergic systems are known to influence the maturation of the higher neuronal systems at specific areas and at specific ages. Particularly the synaptogenesis of the cerebral cortex is modulated by region or layer specifically from an early stage of the development. The observations made in EEG and SEP studies also suggested specific subcortical and cortical involvements taking place during 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 also be explained by the specific features of these monoaminergic systems. Furthermore, analysis of the components of rapid eye movement sleep suggested the onset of RTT lies between 36 gestational weeks to 3–4 months postnatally. The discovery of the mutations of methyl-CpG-binding protein 2 (MECP2) gene as the causative gene of RTT is an epoch helping not only to understand the pathophysiology of RTT but also various neurodevelopmental disorders.