We have over 20,000 different genes in the body, and those genes are located in our DNA. These genes are like instruction manuals for how to build a protein, and each protein has an important function that helps to keep our body working how it should. The MECP2 gene makes a protein called methyl-CpG binding protein 2 (MeCp2). MeCp2 helps to control the expression (activity) of several genes, particularly those which have a role in normal brain function and allow for communication between nerve cells (neurons). 

If someone has a harmful change (called a pathogenic variant) in one of their MECP2 genes, they will have decreased amounts of MeCp2. This may result in decreased gene expression in the brain and may also disrupt the communication between neurons leading to a variety of symptoms, including but not limited to, intellectual disability, problems with coordination, and seizures.

Pathogenic variants in MECP2 are inherited in an X-linked pattern, although most of the time, a pathogenic variant in MECP2 is new (or de novo) and discovered in an affected individual without any family history of the disorder. Rarely, a pathogenic variant may be inherited from a carrier mother who is mildly affected or healthy. When a mother is a known carrier of a pathogenic variant in MECP2, the risk of occurrence in her offspring is 50%. Unfortunately, most males with a MECP2 pathogenic variant have a shortened life expectancy and pass away during infancy. Females with a MECP2 pathogenic variant can present with classic Rett syndrome, variant Rett syndrome, or mild learning disabilities (also referred to as MECP2-related disorders). 

GENETIC TESTING FOR MECP2

Genetic testing for pathogenic variants in MECP2 is currently available, but there are a few different ways to approach testing:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and deletion/duplication analysis: Comprehensive testing to search for all currently detectable pathogenic variants in the gene
• Gene panels: Newer, more broadly based gene tests that would include not only the MECP2 gene, but other genes known or suspected to be associated with similar health complications described in MECP2-related disorders.

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