First Comprehensive Genetic Analysis of Rett Syndrome Reveals Relationship Between Gene Mutations and Symptom Severity

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March 09, 2008
International team conducts largest-ever study examining clinical features of symptoms

(Baltimore, MD) - An international collaboration of scientists has completed the first comprehensive analysis on the clinical effects of the genetic mutations involved in Rett Syndrome, a severe childhood neurological disorder on the autism spectrum caused by mutations in the gene MECP2. The current study, published in the March edition of Neurology, confirms and expands researchers' understanding of the distinctive clinical presentation of specific mutations in Rett syndrome.

Rett Syndrome affects primarily girls, striking at random in early childhood with features of autism and loss of language skills, functional hand use and the ability to walk. The range of MECP2 mutations and variability in clinical presentation in the disorder poses a major challenge to neurologists and physicians. Large-scale studies such as this one address these challenges by examining the relationship between one's genes and how the disorder is expressed in the individual. In the current study, scientists analyzed the eight most common mutations on the MECP2 gene, representing two-thirds of Rett syndrome cases, to determine how they affected the manifestation of these symptoms. The findings show that basic genetic testing is warranted in Rett syndrome not only to confirm the clinical diagnosis but to provide information on the severity of the disorder.

The international team of scientists was led by senior authors Dr. Helen Leonard of the Telethon Institute of Child Health Research in Australia and Dr. Walter E. Kaufmann, Director of the Kennedy Krieger Institute's Center for Genetic Disorders of Cognition & Behavior. Researchers from Spain and Israel also participated in the study. The research was based on data provided by families and clinicians from around the world to the InterRett online database hosted at the Telethon Institute for Child Health Research.

This study provides a more solid base for understanding the clinical presentation and prognosis of a patient with Rett syndrome. Until now, a diagnosis often left parents still wondering to what degree their child would be affected by the disorder. By finding correlations between specific mutations and symptom expression, this study will allow doctors to provide parents with a clearer indication of how the disorder will manifest itself in their child.

The current research expands upon the growing body of knowledge on the disorder. Rett Syndrome is part of the approximately 11 percent of autism spectrum disorders for which genetic causes have been discovered. In 1999, scientists discovered that Rett Syndrome is caused by mutations in the MECP2 gene. Mutations in MECP2 are now being seen in some cases of childhood schizophrenia, classic autism and learning disabilities, meaning insights into Rett Syndrome could have implications for a broad range of disorders. Most recently, in early 2007, a landmark study reversed the symptoms of Rett Syndrome in a genetic mouse model.

About the Kennedy Krieger Institute

Internationally recognized for improving the lives of children and adolescents with disorders and injuries of the brain and spinal cord, the Kennedy Krieger Institute in Baltimore, MD serves more than 13,000 individuals each year through inpatient and outpatient clinics, home and community services and school-based programs. Kennedy Krieger provides a wide range of services for children with developmental concerns mild to severe, and is home to a team of investigators who are contributing to the understanding of how disorders develop while pioneering new interventions and earlier diagnosis. For more information on Kennedy Krieger Institute, visit

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Megan Gallivan

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