GABA Neurons and Rett Syndrome

Rett Syndrome is a rare (1 in every 10,000 to 15,000 live female births) neurodevelopmental disorder that occurs almost exclusively in young girls. This syndrome shares features with autism.  The disorder is caused by a mutation of the MECP2 (methyl-CpG-binding protein 2) gene (MECP2 translation protein diagram noted on the right).  This gene is found on the X chromosome. Infant boys born with the mutation typically die shortly after birth as they have no reserve X chromosome that may compensate to a degree with the mutation.


Rett Syndrome is typically diagnosed in early childhood when the following essential diagnostic criteria are met:

• Normal development until 6 to 18 months of age
• Normal head circumference at birth followed by a slowing of the rate of head growth between 3 months and 4 years of age
• Severe impairment in expressive language
• Repetitive and stereotypic hand movements
• Gait abnormalities--toe walking or wide-based, stiff-legged walk

A recent study published in Nature examined a potential mechanism to explain some of the stereotypical behaviors found in Rett Syndrome.  Using a mouse model, mice were produced that lacked MeCP2 in the brain gamma amino butryic acid (GABA) neurons.  These mice demonstrated a series of neurobehavioral abnormalities similar to Rett syndrome including: repetitive behavior, impaired motor coordination, social interaction abnormalites and reduced startle response.  These mice showed evidence of significant reduction in  GABA content in the brain cortex and striatum regions.


The authors note their study "demonstrate(s) that GABAergic dysfunction is a critical mediator of Rett syndrome phenotypes".  They note that MeCP2 mutations are found in a relatively rare number of humans with bipolar disorder, schizophrenia and autism.  They note that GABAergic dysregulation through a variety of mechanisms may be central to these neuropsychiatric disorders.


If you are interested in learning more about the features of Rett Sydrome, I embedded theYouTube video below that documents the developmental history of Chelsea--an 11 year old girl with Rett Syndrome.





Further information on Rett Syndrome at the International Rett Syndrome Association website as well as from a Fact Sheet on Rett Syndrome from the National Institute of Neurological Disorders and Stroke.


Diagram of MECP2 protein is licensed under the Creative Commons Attribution Share Alike 3.0 unported license with author Emw.


Chao, H., Chen, H., Samaco, R., Xue, M., Chahrour, M., Yoo, J., Neul, J., Gong, S., Lu, H., Heintz, N., Ekker, M., Rubenstein, J., Noebels, J., Rosenmund, C., & Zoghbi, H. (2010). Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes Nature, 468 (7321), 263-269 DOI: 10.1038/nature09582