Description
The Rett syndrome is originally known as cerebroatrophic hyperammonemia. It is a rare genetic disorder which commonly affects women although there are cases where it could be found in male patients. It is considered as a postnatal neurological disorder which affects the grey matter of the brain. Rett syndrome is also considered as a progressive disorder which affects the development of the brain. It is also considered as one of the common cause of mental disorders among women. It occur about 1 in 10,000 births and it typically develops at age 6 to 18 months. The signs or symptoms of the disease commonly appear during the developmental milestone of the infant (U.S. Department of Health And Human Services, 2009).
Rett syndrome was first described by Adreas Rett in 1966. He is an Austrian pediatrician and the disease was named after him. However, it was Huda Zoghbi who concluded that the Rett syndrome was caused by a gene mutation. He is also the one that discovered that the mutation occurs in the gene methyl-CpG-binding protein-2 in 1999. It is classified as a pervasive developmental disorder by the Diagnostic and Statistical Manual of Mental Disorders (DSM). However, it was removed in the DSM-5 in 2013 due to the known molecular etiology.
Signs and Symptoms
In most cases, the initial development of the infant with Rett syndrome is normal. The signs and the symptoms of the disease commonly appear at age between 6 to 18 months. During this period of time, the development of the infant becomes stagnant and it is commonly followed by a developmental regression. In this case, language and motors skills of the child are affected. Hyperventilation and breathing irregularities is a common early sign of the Rett syndrome. After 18 months of age, the symptoms of the Rett disease became similar to other mental disorders such as autism and cerebral palsy. Differential diagnosis could be used in order to identify the specific disease of the infant or the child (National Center for Biotechnology Information, 1998). The main signs or symptoms of the disease are the small feet and hands as well as slow growth rate of the head (Amir, 1999). Other signs of the genetic disorder include repetitive hand movements such as putting the hands inside the mouth. Most of the patients having Rett Syndrome could not walk and do not have verbal skills.
Inheritance of the Disease
The Rett syndrome could be inherited from phenotypically normal mothers. These mothers could have a germline mutation which occurs at the gene encoding methyl-CpG-binding protein-2, or commonly known as the MeCP2. The inheritance of the Rett syndrome is considered as X-linked dominant which is the main reason why it is almost exclusive only in females. In most cases, almost all males which developed a Rett syndrome die shortly after birth. The encoding methyl-CpG-binding protein-2 is found at the terminal portion of the long arm of the X chromosome or at the Xq28. This gene mutates and is the main cause of the typical Rett Syndrome (Amir, 1999).
Gene Locus
The Rett syndrome is commonly caused by a mutation in the gene encoding methyl-CpG-binding protein-2 which is commonly found at the terminal portion of the long arm of the X chromosome or at the Xq28. The methyl-CpG-binding protein-2 is a gene for protein coding which commonly controls the expression of the other genes. It is also known as a “transcriptional repressor” due to its main function. The main effect of the mutation at this gene is the loss of the protein. These proteins are generally important for the development of the child which is why it is common to infants.
The gene methyl-CpG-binding protein-2 could provide the instruction to make the protein MeCP2. This protein is critical for the functions of the brain. The protein MeCP2 is commonly linked to maintaining the synapses which occurs between the brain cells. In general, the brain could not function well without the protein MeCP2.
Known Mutations
The mutations at the methyl-CpG-binding protein-2 are commonly found at the X chromosome from the sperm cells. It is also one of the main reasons why the Rett syndrome is rare in males since they do not commonly inherit the X chromosome from their father. It is also the reason why the the disease is commonly be inherited from phenotypically normal mothers. Unlike the males, the females commonly inherit one copy of the X chromosome from each of their parents. Mutations of the gene generally occur during the development of the fetus and are commonly caused by X-linked dominant inheritance.
In general, the females with Rett syndrome also have one functional copy of the methyl-CpG-binding protein-2 in order to counteract the mutated copy of the gene (National Center for Biotechnology Information, 1998). However, the normal process which is known as the X inactivation could randomly inactivate one of the X chromosomes in every cell. The inactivation of the one of the X chromosome and the specific mutations in the methyl-CpG-binding protein-2 could result in the wide range of symptoms and signs of Rett syndrome (Weaving et al., 2004). The developers of the treatment of the Rett syndrome could use the analysis of the relationship between the methyl-CpG-binding protein-2 and the other proteins which are affected by the mutation.
The mutation of the gene which occurs in the Rett syndrome is only one. The mutation of the methyl-CpG-binding protein-2 could alter the produced protein or it could result to lack of production of protein. The result of the mutation could disrupt the main function of the neurons as well as the other cells in the brain.
Reference
Amir, R. (1999). Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nature Genetics, 23(1): 185-188.
National Center for Biotechnology Information. (1998). Genes and Disease. Retrieved from http://www.ncbi.nlm.nih.gov/books/NBK22188/
U.S. Department Of Health And Human Services. (2009). Rett Syndrome. National Institute of Health. Retrieved from http://www.ninds.nih.gov/disorders/rett/rett_syndrome_brochure_508comp.pdf.
Weaving, L. Ellaway, C., Gecz, J., & Christodoulou, J. (2004). Rett syndrome: clinical review and genetic update. Journal of Medical Genetics, 42(1): 1-7.
