Rare Diseases Clinical Research Center (RDCRC): Rett Syndrome Project
Rett syndrome (RS), a brain disorder affecting development in childhood, has been identified almost exclusively in females. RS results in severe movement and communication problems following apparently normal development for the first six months of life. The characteristic features include loss of speech and purposeful hand use, occurrence of repetitive hand movements, abnormal walking, abnormal breathing, and slowing in the rate of head growth. Current treatment for girls with RS includes physical and occupational therapy, speech therapy, and medication for seizures. No cure for RS is known.
Recently, the National Institutes of Health funded a Rare Disease Clinical Research Network to study RS. The RS clinics at Baylor College of Medicine, the University of Alabama at Birmingham , and Greenwood Genetics Center at Columbia , South Carolina are leading this effort in order to gather information on the natural history of RS from a large cohort of females. This research study is sponsored by National Institutes of Health (NIH). At the present time, effective treatment for RS is lacking. However, recent advances in our understanding of RS suggest that the potential for effective therapies is a realistic future consideration.
In order to be prepared for the implementation of clinical treatment trials, it is important to develop accurate information on the longitudinal (natural history) pattern of progression among individuals with RS. As such, the purpose of this study is to gather detailed historical and physical examination data on a large group of females with RS. In the process, we will also gather information on survival and quality of life. The data will be essential for the proper conduct of future clinical trials. A total of 1000 subjects at 4 institutions will be asked to participate in this study. This study will involve the completion of questionnaires concerning the clinical features of Rett syndrome. These questionnaires have been developed during previous clinical studies and include information such as development, walking abilities, hand use, breathing pattern, growth, seizures, and other features typically observed in girls and women with Rett syndrome.
We will establish a clinical database for the purpose of describing the relationship of the mutation in the MeCP2 gene to the clinical characteristics of the girl (phenotype-genotype correlations). MeCP2 is a gene on the X- chromosome. We will compare the type of mutation in the MeCP2 gene and the clinical features of the girl or woman with Rett syndrome. This will allow us to determine if specific mutations (genotype) are associated with more or less severe clinical features (phenotype). Potential participants are expected to have had determination of their MECP2 mutation status.
Information gathered from these visits will be sent to the Rare Disease Clinical Research Network's Data and Technology Coordinating Center (DTCC) located at the University of South Florida.
Relevance of the project to IDDRC mission:
Girls with Rett syndrome (RS) typically have developmental disorders characterized by loss of spoken communication skills, and purposeful hand use; epilepsy. Additionally, these girls frequently have features of autism and understanding the genetics basis of this disorder may further our knowledge of other disabilities.