Abstract
Assessment of the development of motor function of Rett syndrome (RTT) revealed hypotonia
with failure of crawling and disturbance in skillful hand manipulation are shown as
early motor signs. Clinical evaluation has revealed the former as postural hypotonia
with failure in locomotion and neurophysiological examinations have showed this to
be due to hypofunction of the aminergic neurons of the brainstem. The latter signs
are considered to indicate dysfunction of the corticospinal tract at higher levels.
As the signs appear along with deceleration of head growth, dysfunction of the noradrenergic
neuron, which is involved in synaptogenesis in the cerebral cortex, is postulated
as the cause. The characteristic stereotyped hand movements appear in early childhood
after loss of purposeful hand use and are underlain by rigid hypertonus. Neurophysiological
examinations have indicated that these are due to hypofunction of the nigrostriatal
(NS) dopamine (DA) neuron. By comparison with animal experimental work the neurohistochemical
changes in the substantia nigra of the autopsied brain of RTT suggest a lesion caused
by the dysfunction of the pedunculopontine nucleus, induced by dysfunction of the
brainstem aminergic neurons which modulate postural tone and locomotion. Hypofunction
of the aminergic neurons also cause ‘leakage’ of atonia into nonREM stages which lead
to disturbances in the autonomic nervous system through inhibition of the reflex system.
The grade of disturbance of locomotion closely matches the grade in abnormalities
of higher cortical function as indicated by the development of meaningful words. The
loci of missense mutation of methyl CPG binding domain of MECP 2gene which affect locomotion severely also markedly impaired their effects on the
formation of the heterochromatin. Thus, dysfunction of the aminergic neurons of the
brainstem which regulate postural tone and locomotion is proposed as the primary lesion.
Keywords
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Article info
Publication history
Accepted:
November 1,
2004
Received:
September 20,
2004
Identification
Copyright
© 2005 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
