Rett syndrome: Review of biological abnormalities

The Rett syndrome (RS) is a peculiar, sporadic, atrophic disorder, almost e ntirely confined to females. After the first six months of life there is de velopmental slowing with reduced communication and head growth for about on e year. This is followed by a rapid destructive stage with severe dementia and loss of hand skills (with frequent hand wringing), apraxia and ataxia, autistic features and irregular breathing with hyperventilation. Seizures o ften supervene. Subsequently there is some stabilization in a pseudo-statio nary stage during the preschool to school years, associated with more emoti onal contact but also abnormalities of the autonomic and skeletal systems. After the age of 15-20 years, a late motor deterioration occurs with dyston ia and frequent spasticity but seizures become milder. RS has generally bee n considered an X-linked disorder in which affected females represent a new mutation, with male lethality. Linkage studies suggested a critical region at Xq28. In 1999, mutations in the gene MECP2 encoding X-linked methyl cyt osine-binding protein 2 (MeCP2) were found in a proportion of Rett girls. T his protein can bind methylated DNA. Analyses are leading to much further i nvestigation of mutants and their effects on genes. Neuropathological and e lectrophysiological studies of RS are described. Description of neurometabo lic factors includes reduced levels of dopamine, serotonin, noradrenaline a nd choline acetyltransferase (ChAT) in brain, also estimation of nerve grow th factors, endorphin, substance P, glutamate and other amino acids and the ir receptor levels. The results of neuroimaging are surveyed, including vol umetric magnetic resonance imaging (MRI) and positron emission tomography ( PET).