Clinical Trial: Biobanking of Rett Syndrome and Related Disorders

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Biobanking of Rett Syndrome and Related Disorders Protocol

Brief Summary: The overarching 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. Although all these disorders are the result of specific genetic changes, there remains broad clinical variation that is not entirely accounted for by known biological factors. Additionally, clinical investigators currently do not have any biomarkers of disease status, clinical severity, or responsiveness to therapeutic intervention. To address these issues, biological materials (DNA, RNA, plasma, cell lines) will be collected from affected individuals and in some cases from unaffected family members, initial evaluation performed to identify additional biological factors contributing to disease severity, and these materials will be stored for future characterization.

Detailed Summary:

At the present time, effective treatments for RTT, MECP2 Dup, or Rett-related disorders are lacking. Investigators have made substantial progress 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, investigators became aware of additional MECP2- and RTT-related disorders that were unknown at the time the original proposal was conceived and further were impressed by the substantial clinical variability in individuals with RTT that cannot be explained by differences in mutations alone. In fact, variability among individuals with identical mutations has led investigators to 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, investigators were not aware of the variation in clinical disorders related to MECP2 mutations or to the related but quite different MECP2 Dup. 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. The investigators propose in this new study to build on the substantial progress made in understanding both classic and variant RTT and to add these related disorders, MECP2 Dup and t
Sponsor: University of Alabama at Birmingham

Current Primary Outcome:

  • X-chromosome inactivation in Rett syndrome (RTT) [ Time Frame: 5 years ]
    Characterize X-chromosome inactivation in RTT and correlate with clinical severity.
  • Bdnf polymorphisms in RTT [ Time Frame: 5 years ]
    Characterize Bdnf polymorphisms in RTT and correlate with clinical severity.
  • Inflammation markers in MECP2 duplication syndrome [ Time Frame: 5 years ]
    Evaluate inflammation markers in MECP2 duplication syndrome and correlate with disease severity.
  • Biobanking of blood for Rett syndrome (RTT), MECP2 duplication syndrome, FOXG1, CDKL5, and MECP2 mutations not producing RTT [ Time Frame: 5 years ]
    Blood will be collected and stored from participants with RTT, MECP2 duplication, FOXG1, CDKL5, and MECP2 mutations without RTT to analyze factors noted in Outcomes 1-3 and in secondary outcome 5 to correlate with disease severity.


Original Primary Outcome: Same as current

Current Secondary Outcome: Breakpoints and gene content of MECP2 and FOXG1 duplications [ Time Frame: 5 years ]

Characterize breakpoints and gene content of MECP2 and FOXG1 duplications and correlate with disease severity


Original Secondary Outcome: Same as current

Information By: University of Alabama at Birmingham

Dates:
Date Received: November 22, 2015
Date Started: December 2015
Date Completion: December 2019
Last Updated: December 6, 2016
Last Verified: October 2016