Rett syndrome is a clinically defined disorder associated with an apparent decline in cognitive and motor skills, generally beginning between 6 and 18 months of age and typically following a period of apparent development normality. The disorder appears to be unique to girls although """"""""atypical cases"""""""" have been reported in males. During an early stage of their course, many of these patients have shown autistic- like features. This syndrome affects approximately 1/10,000 girls and is known to have a world-wide distribution. The cause of Rett syndrome is unknown but genetic factors are strongly suspected. Early anatomic studies of the brain in Rett syndrome have shown inconsistent findings and the abnormalities that were described were insufficient to explain the multiple behavioral and neurological symptoms of the disorder. More recent studies have suggested widespread neuroanatomic abnormalities throughout the entire brain which appear to be consistent with a curtailment of brain development. Further, there is evidence to suggest that these abnormalities may correlate more closely with the clinical presentation than with duration of symptomatology or chronological age of the patient. We propose to systemically study the brains of 10 additional girls with Rett Syndrome and that of a symptomatic male sibling of a Rett girl who is believed to represent an """"""""atypical case."""""""" These brains will be processed in gapless serial section and studied in comparison with identically processed ago and sex-matched controls and with identically processed autistic cerebra. Measurements of neuronal cell size and cell packing density will be made in selected areas of the Rett, autistic and control brains by means of a 3-dimensional computerized cell counting system. Similar analysis of glial cells will be made in GFAP prepared sections. Neuronal cell structure and the extent and complexity of the dendritic tree will be analyzed in selected areas of each brain using the rapid Golgi technique and studied in comparison with controls. Abnormalities of cortical lamination and myelination will also be sought. Evidence for timing of onset, morphologic differences and similarities between brains, and the relationship of the atypical case to the girls with the classical presentation of this disorder will be considered. It is expected that patterns of altered cytoarchitecture will emerge which will provide an explanation for some of the clinical features of this syndrome and clues to the time of onset, etiology and directions for future research.
Showing the most recent 10 out of 76 publications
