Who can get Rett syndrome?

Rett syndrome is estimated to affect one in every 10,000-15,000 live female births and in all racial and ethnic groups worldwide. Prenatal testing is available for families with an affected daughter who has an identified methyl CpG binding protein 2 (MECP2) mutation. Since the disorder occurs spontaneously in most affected individuals, the risk of a family having a second child with the disorder is less than 1 percent.

Genetic testing is also available for sisters of girls with Rett syndrome who have an identified methyl CpG binding protein 2 (MECP2) mutation to determine whether they are asymptomatic carriers of the disorder, which is an extremely rare possibility.

The MECP2 gene is found on a person's X chromosome, one of the two sex chromosomes. Girls have two X chromosomes, but only one is active in any given cell. This means that in a girl with Rett syndrome, only a portion of cells in the nervous system will use the defective gene. Some of the child's brain cells use the healthy gene and express normal amounts of the protein.

The severity of Rett syndrome in girls is in part a function of the percentage of their cells that carry a normal copy of the MECP2 gene. If the active X chromosome that is carrying the defective gene is turned off in a large proportion of cells, symptoms will be mild, but if a larger percentage of cells have the X chromosome with the normal MECP2 gene turned off, the onset of the disorder may occur earlier and symptoms may be more severe.

The story is different for boys who have a MECP2 mutation known to cause Rett syndrome in girls. Because boys have only one X chromosome (and one Y chromosome), they lack a backup copy that could compensate for the defective one and they have no protection from the harmful effects of the disorder. Boys with such a defect do not show clinical features of Rett syndrome frequently but experience severe problems when they are first born and die shortly after birth. A very small number of boys may have a different mutation in the MECP2 gene or a sporadic mutation after conception that can cause some degree of intellectual disability and developmental problems.

This answer is based on source information from the National Institute of Neurological Disorders and Stroke.