Pathophysiology of Rett syndrome from the stand point of clinical characteristics

In this report, we reviewed the characteristics of motor development and motor symptoms of Rett Syndrome (RTT) and demarcated the early and pathognomonic motor symptom which correlates to the impairment of the higher cortical function (HCF) assessed by the ability of language. It is suggested that failure of locomotion in late infancy is the primary and pathognomonic symptom. Thus, the impairment of the neurons or neuronal systems involving locomotion is suggested as the primary lesion in the pathophysiology of RTT not only for motor dysfunction but also for the failure in the development of language and cognitive function. On the other hand the neuronal systems involving the loss of purposeful hand use and the stereotyped hand movement, the most characteristic and diagnostic symptoms of RTT appearing in early childhood, are affected later or secondarily but induce further degradation of the HCF. Hypofunction of the aminergic neurons in the brainstem and midbrain is suggested as the cause of dysfunction of these neuronal systems, for those of locomotion, the noradrenarlin (NA) and/or the serotonin (5HT) neurons and for the stereotyped hand movement the dopamine (DA) neurons. The NA and/or the 5HT neurons in the brain stem may be involved primarily and may cause dysfunction of the midbrain DA neuron directly or indirectly through affecting the pedunculopontine nuclei.