Survey of MeCP2 in the Rett Syndrome and

In Rett syndrome,1 there are clinical and neuropathologic observations suggesting that an arrest of brain develop-ment is responsible for the phenotype.2 At age 3 months, the apparently normal infant shows a decrease in head cir-cumference.3 The toddler with Rett syndrome fails to develop speech, hand use, and normal gait4,5 or loses these abilities shortly after acquiring them. Studies of cerebral blood flow show a persistence of the infantile pattern,6 and in vivo magnetic resonance images (MRIs) exhibit a global reduc-tion in the volume of gray and white matter.7 Neuropatho-logic studies confirm the reduction in brain volume, with the average brain weight remaining in the range of 950 g, that of a normal 12-month-old infant.8 There is no obvious atro-phy or degeneration to account for the small brain size.9 Bau-man et al10 and Belichenko11 observed reduced neuronal size in the hippocampus-entorrhinal cortex and in the speech-related cortex (areas 40, 45, and 22), respectively. Arm-strong et al observed less dendritic branching in the neurons of layers III and V in the frontal, motor, subicular, and infe-rior temporal cortices.12,13 Also, the neurotransmitter profiles in the Rett syndrome brain resemble those of an immature brain.14–18 However, in spite of these clinical and morphologic features that suggest a hypothesis of arrested brain devel-opment in Rett syndrome, other aspects do not support this idea. For example, the neuroendocrine system matures, with menarche developing on schedule, making reproduc-tion by women with Rett syndrome possible.19 The den