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Summary

at Oakland, California and other locations
study started
estimated completion:

Description

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).

Official Title

Rett Syndrome, MECP2 Duplication Disorder, and Rett- Related Disorders Natural History Protocol

Details

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.

Keywords

Rett Syndrome MECP2 Duplication dIsorder RTT-related Conditions

Eligibility

You can join if…

  • 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.

You CAN'T join if...

  • Individuals who do not meet the above criteria will be excluded.

Locations

  • University of California San Diego accepting new patients
    San Diego, California, 92123, United States
  • University of Colorado Denver accepting new patients
    Denver, Colorado, 80045-2571, United States
  • Baylor College of Medicine accepting new patients
    Houston, Texas, 77030, United States
  • Gillette Children's Specialty Healthcare accepting new patients
    Saint Paul, Minnesota, 55101, United States
  • Washington University School of Medicine and St. Louis Children's Hospital accepting new patients
    Saint Louis, Missouri, 63110-1093, United States
  • Rush University Medical Center accepting new patients
    Chicago, Illinois, 60612, United States
  • Vanderbilt University accepting new patients
    Nashville, Tennessee, 37212, United States
  • University of Alabama at Birmingham accepting new patients
    Birmingham, Alabama, 35294, United States
  • Cincinnati Children's Hospital Medical Center accepting new patients
    Cincinnati, Ohio, 45229, United States
  • Cleveland Clinic not yet accepting patients
    Cleveland, Ohio, 44195, United States
  • Greenwood Genetic Center accepting new patients
    Greenwood, South Carolina, 29646, United States
  • University of Rochester accepting new patients
    Rochester, New York, 14627-0140, United States
  • Children's Hospital of Philadelphia accepting new patients
    Philadelphia, Pennsylvania, 19104-4318, United States
  • Children's Hospital Boston accepting new patients
    Boston, Massachusetts, 02115, United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
University of Alabama at Birmingham
Links
International Rett Syndrome Foundation website
ID
NCT02738281
Study Type
Observational
Last Updated
May 1, 2017
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