Most cases of Rett syndrome are caused by a genetic mutation that affects a gene called MECP2 present on the X chromosome.
This gene codes for the MeCP2 protein, which is essential for the normal development of nerve cells in the brain. Rett syndrome affects one in every 10,000 to 12,500 females by the age of 12 years.
The mutation that causes this condition arises in one of two ways:
- As a sporadic or “de novo” mutation, meaning it is not inherited and occurs in individuals with no family history of the condition. Almost all cases of Rett syndrome are caused by a sporadic mutation.
- As a germline mutation inherited from mothers who are phenotypically normal but have a mutation in the MECP2 gene, which is located on the long arm of the X chromosome.
Usually, females have two X chromosomes in each of their cells and males have one X and one Y chromosome. However, only one of the X chromosomes is ever fully functional in a cell, either way.
In females, one of these X chromosomes is mainly inactive during embryonic development and this inactivation occurs randomly. Rett syndrome occurs in cases where one X chromosome with a normal MECP2 gene leads to half a child’s brain cells working properly, while an MECP2 mutation present on the other X chromosome causes the other half of the child’s brain cells to be abnormal and not function properly.
On rare occasions, cases of Rett syndrome are seen in males when the child is born with more than one X chromosome (an XXY configuration), a condition referred to as Klinefelter's syndrome.