[Rett's syndrome. Clinical features and advances in genetics]

Rett's syndrome (RS) is a disorder of neurological development which is the second commonest cause of mental retardation in girls. It is normally caused by de novo mutations of a gene on the X chromosome. This gene encodes for the protein joining the methyl CpG (MECP2). Mutations of this gene have been found in approximately 80% of the cases confirmed as having the classical form of RS. Mutations of the gene MECP2 were also found in about a third of the nonclassical cases of RS and in other conditions: women with mild or severe mental retardation, children with autism, even children with neonatal encephalopathy or with a clinical condition similar to RS.

Studies correlating the genotypes and phenotypes in classical RS suggest that the pattern of inactivation of the X chromosome is more important in determining the severity of the condition than the type or site of the mutation. However, when we consider all the phenotypes associated with mutations of MECP2, it is seen that the type of mutation correlates to a certain degree with the clinical onset and severity of the disorder.

Recent advances in the genetics of RS therefore have specific application in the clinical field. They give further markers for diagnosis and possibly indicate the prognosis, as well as being useful in genetic counselling for the families of patients with RS.