Molecular Approaches to the Rett Syndrome Gene

Abstract

Rett syndrome is a neurodevelopmental disorder affecting 1 in 10,000 to 15,000 females worldwide. Apparently normal at birth, girls with Rett syndrome undergo developmental regression and acquire a neurologic and behavioral profile that has been used to define diagnostic criteria for the disorder. Neurochemical and anatomic alterations indicate that Rett syndrome appears to result from an arrest of normal neuronal maturation. Although Rett syndrome generally occurs sporadically, rare familial recurrences indicate a genetic basis for the disorder. Data from familial recurrences are consistent with an X-linked dominant locus causing the classic phenotype in female patients and a distinct, more severe phenotype in hemizygous male patients. Exclusion mapping data from rare kindreds with recurrent Rett syndrome localize the gene to the distal long arm of the X chromosome (Xq27.3-Xqter). (J Child Neurol 1999; 14:806-814).