Rett syndrome (RTT) is an X-linked dominant neurodevelopmental disorder affecting almost exclusively girls. Mutations in the MECP2 gene have been found in a variety of different RTT phenoty- pes. The MECP2 gene encodes a transcriptional repressor (MeCP2, methyl-CpG-binding protein 2) acting by binding to the methylated DNA and producing the compacted chromatin structure. MeCP2 is strongly expressed in brain. Up to now, 370 different MECP2 mutations have been reported. Most mutations occur de novo on the paternal chromosome. In several cases a genotype-phenotype correlation have been found.