Clinical Manifestations of Rett Syndrome Essay

Rett Syndrome is neurodevelopment condition that causes female intellectual. The disorder causes seizures, mental retardation and affects motor and speech skills. The signs of the syndrome occur in different stages with the patient growing normally in the first 6 months after birth. Between 6 and 18 months, the onset stage, which is the first stage, occurs; some of the symptoms include a loss of interest in playing with toys and delays in movements involved during crawling and sitting.

The deterioration stage is the second stage which occurs to kids who are within age of 1 to 4 years. Symptoms in deterioration stage include hyperventilation, uncontrolled screaming, challenges in coordination and movement, sluggish head, and reduced social interaction. After the deterioration phase, the plateau phase, which is the third stage occurs; this occurs to girls whose age is between 2 to 10 years. Seizures start to occur in the third stage; some patients experience improved hand movement and the ability to communicate. After the age of ten years, the syndrome progresses to the 4th stage which is the late motor deterioration stage. During this stage, there is reduced occurrence of seizures with patients experiencing muscle weakness and reduced mobility. Scoliosis is also observed in some patients during the fourth stage. Some of the symptoms experienced during the early stages stabilize and occur less frequently as the child grows.

The disease is triggered by a random change in gene structure which occurs in the MECP2 gene. The syndrome is linked to the X-chromosome since the altered gene that causes its occurrence is found in the X-chromosome. The gene mutation affects the development of proteins that are linked with the development of the brain in females (Amir et al., 1999). When a mutation occurs on the MECP2 gene, the MECP2 proteins encoded in it are unable to deactivate some genes from being decoded in the body. An alteration of one gene is enough to cause the syndrome. This alteration occurs when one of the genes is decoded.

The occurrence of the mutations that cause Rett syndrome has been observed to occur on the whole stretch of MeCP2 which holds two useful domains: A C-terminal domain which represses the transcription and an N-terminal methyl –CpG unalterable domain. In patients suffering from Rett syndrome, there is a common occurrence of the cancelation of the C terminal domain; this causes loss of binding of the FBP11 and HYPC splitting factors. Encoding of the methyl –CpG- binding protein 2 (MeCP2) which is mapped to Xq28 by the MECP2 gene is considered a common reason for occurrence of Rett syndrome (Amano, Nomura, Segawa, & Yamakawa, 2000). The X-linked dominant MECP2 ends up causing genetic mutation and consequently, Rett syndrome.

Based on laboratory studies done using mice, there is evidence supporting the function of MeCP2 in transcriptional repression.

Laboratory results indicated the presence of clearly defined TRD which is mapped to 207-310 amino acids. Shortening of the TRD by even ten C-terminus amino acids with termination at 300 amino acids can cause complete loss of repression activity. Transcriptional repressor activity needed for a fully intact and functional TRD was not displayed in MeCP2 –R270 and MeCP2-G273X (Weaving, 2005). Most mutations that cause the disease affect the functional regions of the MeCP2 gene, complete deletion or a micro deletion of the TRD domain can cause the disease to occur (Baker, et al., 2013). Changes in the amino acids contained in the TRD domain can also change the functioning of this protein resulting in phenotypic variability that can cause other diseases apart from Rett syndrome.

The symptoms experienced by the patients are determined by the type of mutations with patients having T158M, 201GlyFS-235X and R168X. These mutations occur inside or near the MBD domain having their mobility affected more than others. The stages of the disease are determined by the level of mutation.

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Amano, K., Nomura, Y., Segawa, M., & Yamakawa, K. (2000). Mutational analysis of the MECP2 gene in Japanese patients with Rett syndrome. Journal of Human Genetics,45(4), 231-236. doi:10.1007/s100380070032
Amir, R., Van den Veyver, I., Wan, M., Tran, C., Francke, U., & Zoghbi, H. (1999). Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nature Genetics, 23(2), 185-188. doi: 10.1038/13810
Baker, S., Chen, L., Wilkins, A., Yu, P., Lichtarge, O., & Zoghbi, H. (2013). A Newly Characterized AT-Hook Domain in MeCP2 Determines the Clinical Course of Rett Syndrome and Related Disorders. Cell,152(5), 984-996. doi:10.1016/j.cell.2013.01.038
Weaving, L. S. (2005). Rett syndrome: Clinical review and genetic update. Journal of Medical Genetics,42(1), 1-7. doi:10.1136/jmg.2004.027730