Anatomy of rett syndrome

Abstract

Rett syndrome is a clinical entity with a distinct set of signs and symptoms. Its etiology is unknown. We review here our observations in this disorder based upon clinical and polysomnographic examinations which are consistent with a developmental disorder of the monoaminergic neural system. These studies argue for a disorder of the noradrenergic, serotonergic and dopaminergic system arising in the locus ceruleus, raphe nuclei and substantia nigra, respectively. Because events of rapid eye movement sleep appear not disturbed, except for body movements, cholinergic neurons are probably not affected. Disordered physiologic states appear in a characteristic sequence with advancing age. Clinical symptoms associated with the aberrant caudally located neurons appear early and those rostrally located become manifested later. This caudalorostra1 developmental process attributable to early lesion of monoaminergic neurons may explain the age-related sequence of symptoms of Rett syndrome.

Diabetes mellitus type 1: association with Rett syndrome

“…The discovery of the causative gene for Rett syndrome, X‐linked Methyl CpG binding protein 2 5 , provides a strong confirmatory tool for the diagnosis of RTT and also clarifies the broadness of phenotypic variation of this syndrome. However, the clinical characteristic of the age‐related occurrence of particular symptoms 6–8 is essential for diagnosis. In our patient, we diagnosed Rett syndrome with the clinical signs and symptoms.…”

Natural History of Rett Syndrome

“…[2][3][4] The neurophysiologic examination of sleep-wake rhythm and sleep parameters measured by polysomnography revealed the characteristic features that supported the underlying pathophysiology of age-dependent modification. 12,13 On the basis of these observations, we suggested that the onset of Rett syndrome was in early infancy. The syndrome's pathophysiology reveals that it is a developmental disorder caused by early dysfunction of brainstem aminergic neurons (ie, hypofunction of the serotonergic neurons [5-hydroxytryptamine] and the noradrenergic neurons).…”

“…Both gross movements and twitch movements revealed different patterns between patients younger than 6 years of age and older than that. 12 Frequencies of twitch movements in REM stage in younger children showed a decrement, suggesting hypofunction of dopaminergic transmission, but older patients showed an increment, suggesting an increase in dopaminergic transmission owing to the occurrence of supersensitivity of dopaminergic receptors.…”

General discussion

“…Autistic features in early infancy as the initial sign of RS has been emphasized by Nomura et al (80,81,83). Recently (82) they noted subtle autistic behaviour and muscle hypotonia in early infancy and proposed dysfunction of noradrenergic neurons at the brain stem and midbrain level as the initial locus of disease in RS.…”