Rett syndrome (RTT) is a neurodevelopmental disorder characterised by early onset developmental stagnation (6 months-1.5 year) followed by developmental regression and motor deterioration. It is the most frequent cause of progressive mental retardation in girls and is lethal in males. RTT appears to occur predominantly in females with a prevalence rate of 1/10,000-1/15,000 female births. However, rare cases have been reported in males with somatic mosaicism or an extra X chromosome. Loss of acquired skills such as speech, purposeful hand use, and intellectual disability is observed in those affected. Other clinical features displayed include microcephaly, seizures, spasticity, ataxia, bruxism and breath-holding attacks.
Rett Syndrome results from a mutation on the X chromosome that is transmitted as an X-linked trait. However, most cases are thought to represent new mutations that appear sporadically. The major gene involved is the methyl CpG binding protein-2 (MECP2) gene, found on chromosome band Xq28. The normal MCEP2 gene encodes a protein MeCP2, which binds to methylated DNA, and activates histone deactylase. The mutated gene produces loss of function of this protein causing unregulated expression of certain genes involved in nervous system development.