Unlike Rett Syndrome, which is caused by mutations or deletions in the MECP2 gene, the symptoms that arise from the duplication syndrome are caused, as the name suggests, by having an area of the X chromosome (Xq28), which includes the MECP2 gene, erroneously duplicated. The section duplicated may vary from individual to individual and may also contribute to the severity of the disease.
The syndrome has been diagnosed mostly in boys. The majority inherits the duplication from their mothers who are typically asymptomatic due to favorable X chromosome inactivation (the moms have inactivated the X chromosome that harbors the duplication). Carrier mothers have a 50% chance of passing on the duplication to their children.
The MECP2 Duplication Syndrome may be quite prevalent. Preliminary studies suggest that 1% of cases of X-linked intellectual disability may be due to this syndrome. The core phenotypes in boys include infantile hypotonia, mild dysmorphic features, developmental delay, absent to minimal speech, recurrent infections, progressive spasticity especially of the lower limbs, ataxia, autistic features, and seizures. Females with MECP2 duplication without X chromosome inactivation skewing have been reported and present similarly to boys.
MECP2 Duplication Syndrome Fund at RSRT
In an effort to immediately leverage RSRT’s deep knowledge base and well established global scientific networks the MECP2 Duplication Syndrome Fund at RSRT was created in late 2010. The Fund puts the intellectual and scientific resources of RSRT immediately to work for the MECP2 Duplication/Triplication Syndrome community.
The Fund exclusively supports projects devoted to the study and means of treatment of MECP2 Duplication Syndrome. 100% of every dollar contributed is invested in research – not a single penny goes to overhead.
In 2012, a parent-driven effort was established to raise funds for the initial reversal experiments conducted at the Baylor College of Medicine. Families pledged to raise $401 to cover the cost of the experiments. The initiative was a success, and the 401 Project was born. All funds raised through the 401 Project initiative are directly deposited into the MECP2 Duplication Syndrome Fund at RSRT.
To date the MECP2 Duplication Syndrome Fund has raised $2,068,247.
The current goal is to quickly raise $300,000 to fund research in the lab of Huda Zoghbi. She is working collaboratively with the biotech company, Ionis Pharmaceuticals, to develop an ASO (antisense oligonucleotide) that can bring down the levels of the MECP2 protein. The Zoghbi lab is working on several key experiments that are critical next steps before a clinical trial can be initiated.