This paper reviews the main genetic, neurochemical, neuropathological
and neurophysiological studies on Rett syndrome (RS), a disorder of th
e early childhood characterized by a progressive loss of cognitive and
motor skills as well as the development of stereotypic hand movements
. Although the mode of transmission of RS is unclear, it has been asso
ciated to two loci, one on the X chromosome and other autosomal, possi
bly on chromosome 11. Likewise, it has been suggested that mitochondri
al DNA (DNAmt) and genes encoding neural growth factors and their rece
ptors may be relevant to RS. On the other hand, from a neurochemical p
oint of view, although findings are not concordant, it has been descri
bed in RS the presence of abnormalities in dopamine function as well a
s a primary deficit in the functioning of cholinergic system. Neuropat
hological studies in patients with RS have confirmed the existence of:
(a) a generalized brain atrophy involving the cerebrum and cerebellum
; (b) a decrease in neuronal cell size and an increased cell packing d
ensity; (c) a reduction in the number of basal forebrain cholinergic n
eurons, and (d) a reduction in the concentration of melanin-containing
neurons in the substantia nigra. Finally several neurophysiological s
tudies have demonstrated irregularities of breathing during wakefulnes
s in patients with RS, suggesting a cortical involvement in the brains
tem respiratory control.