Coffin-Lowry syndrome (CLS, MIM#303600) is an X-linked semidominant disorder. In males disorder is characterized by severe mental retardation with distinctive phenotype of face and hands, and with abnormalities in osteoarticular system. In females the intensity of symptoms is variable. Coffin- Lowry syndrome is caused in the majority of cases by mutations in the RSK2 gene (RPS6KA3) located in Xp22.2 region. The RSK2 gene encodes for RSK2 protein that belongs to a family of serine-threonine kinases acting in the MAPK/ERK signalling pathway.

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.