Anatomy of Rett syndrome

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 caudalorostral developmental process attributable to early lesion of monoaminergic neurons may explain the age-related sequence of symptoms of Rett syndrome.