Natural History of Rett Syndrome & Related Disorders

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Disease Information

Descriptive Information
Brief Title † Natural History of Rett Syndrome & Related Disorders
Official Title † Rett Syndrome, MECP2 Duplication Disorder, and Rett- Related Disorders Natural History Protocol
Brief Summary The purpose of this study is to advance understanding of the natural history of Rett syndrome (RTT), MECP2-duplication disorder (MECP2 Dup), RTT-related disorders including CDKL5, FOXG1, and individuals with MECP2 mutations who do not have RTT including the range of clinical involvement and to correlate genotype-phenotype over a broad spectrum of phenotypes. While much has been learned about RTT, improvements are required in understanding the role of factors such as X chromosome inactivation, genetic background, and others including the environment, on the great variability observed even between individuals with the same MECP2 mutation. These data will be essential to the development and conduct of clinical trials that are anticipated from ongoing studies in animal models for RTT. This study will not include clinical trials, but should set the stage for such trials and other translational research projects (e.g., development of biomarkers).
Detailed Description At the present time, effective treatments for RTT, MECP2 Dup, or Rett-related disorders are lacking. Substantial progress has been made in RTT over the past eleven years such that this study represents a narrowing of focus to mutations or duplications of the MECP2 gene and related disorders, including those with phenotypic overlap. Understanding of RTT has advanced remarkably well through the Rett Syndrome Natural History Clinical Protocol (NHS) and correspondingly advancement in the basic science realm has moved forward with equivalent success. Thus, progress in clinical and basic science has led to the establishment of clinical trials and other translational studies that hold promise for additional clinical trials in future. In the process, however, additional MECP2- and RTT-related disorders that were unknown at the time the original proposal have been identified. In addition, substantial clinical variability in individuals with RTT that cannot be explained by differences in mutations alone must be explored further. In fact, variability among individuals with identical mutations has led to the search for additional explanations. At the time of the initial application (2002), just three years after the identification of the gene, MECP2, as the molecular link to RTT, the variation in clinical disorders related to MECP2 mutations or to the related but quite different MECP2 Dup were unknown. Each disorder is characterized by significant neurodevelopmental features related either to alterations in the MECP2 gene or related to phenotypes closely resembling those seen in individuals with RTT. Further, the phenotypic overlap with RTT due to mutations in CDKL5 and FOXG1 was also unexplored. This new study will build on the substantial progress made in understanding both classic and variant RTT and to add these related disorders, MECP2 Dup and the Rett-related disorders including CDKL5, FOXG1, and individuals with MECP2 mutations who do not have RTT. A comprehensive clinical research program will be performed including clinical, neurophysiologic, and molecular and biochemical markers across these different, but related disorders. This protocol will address the natural history components only and will serve as the basis for other study protocols including the neurophysiologic and biomarker studies. Thereby, these studies will represent a continuing pathway to focus and inform not only the ongoing but also the emerging clinical trials.
Study Phase N/A
Study Type † Observational
Study Design †
Primary Outcome Measure † Clinical longitudinal assessments in Rett syndrome (RTT) as measured by mean growth over 5 years.
Secondary Outcome Measure † Quality of Life Measures in RTT
Condition † Rett Syndrome MECP2 Duplication dIsorder RTT-related Conditions
Intervention †
Study Arms / Comparison Groups Rett Syndrome This is a prospective natural history study examining the phenotypic variations of individuals with mutations in MECP2 or meeting the diagnostic criteria for classic (typical) or variant (atypical) Rett syndrome. The overwhelming majority will be female, but males meeting diagnostic criteria will be included. No interventions are planned. MECP2 Duplication This is a prospective natural history study examining the phenotypic variations of individuals with MECP2 duplications. The majority are expected to be males, but females expressing a duplication will be included. No interventions are planned. RTT related disorders This is a prospective natural history study examining individuals, both females and males who do not meet criteria for Rett syndrome, but have a mutation in MECP2, CDKL5, or FOXG1. No interventions are planned.
Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information
Recruitment Status †
Estimated Enrollment † 1200
Start Date † November 2015
Completion Date December 2019
Primary Completion Date July 2019
Eligibility Criteria † Inclusion Criteria: - Individuals of both genders and of all ages, with RTT, MECP2 Dup, and, RTT-related disorders including those with mutations or deletions in CDKL5 and FOXG1 genes, or those with RTT (atypical or typical) who are mutation negative. Exclusion Criteria: - Individuals who do not meet the above criteria will be excluded.
Gender All
Ages N/A - N/A
Accepts Healthy Volunteers No
Contacts †† Alan K Percy, MD, 2059964927,
Location Countries † United States
Administrative Information
NCT ID † NCT02738281
Organization ID RDCRN 5211
Secondary IDs ††
Responsible Party Principal Investigator
Study Sponsor † University of Alabama at Birmingham
Collaborators †† National Institutes of Health (NIH)
Investigators † Principal Investigator: Alan K Percy, MD, University of Alabama at Birmingham
Information Provided By
Verification Date May 2017
First Received Date † November 22, 2015
Last Updated Date May 18, 2017
† Required WHO trial registration data element.
†† WHO trial registration data element that is required only if it exists.
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