Understanding Rett Syndrome

A genetic disorder results from a pathogenic variant or mutation in an individual’s genetic information, also known as DNA. DNA contains genes, which provide the instructions for making proteins that drive the body’s growth and development. This DNA is stored in the body in structures called chromosomes.

Individuals typically have 23 pairs of chromosomes, with one chromosome from each pair coming from the mother and one from the father. All but one of these chromosomes are the same in males and females. In the 23rd pair of chromosomes, males have an X and a Y chromosome while females have two X chromosomes.

Rett syndrome is caused by a pathogenic variant in the MECP2 gene located in the X chromosome.

Every cell in our body has the MECP2 gene which provides instructions to make the MeCP2 protein. MeCP2 stands for methyl-CpG binding protein 2. It plays a crucial role in regulating other genes essential for brain cell function, building connections between neuronal cells during brain development, and maintaining these connections throughout life.

Pathogenic variants in the MECP2 gene result in the MeCP2 protein being absent or non-functional. Though Rett syndrome affects multiple organ systems, the most significant impact is seen on brain development, impacting how brain cells communicate and grow. More than 800 unique variants in the gene have been found to cause Rett syndrome.

Pathogenic variants in the MECP2 gene are currently believed to be de novo in 99% of cases. That means that the variant is new or spontaneous, not known to be inherited from a parent except in incredibly rare cases. Additionally, having another child with Rett syndrome is incredibly rare, the risk estimated to be <1%