Genetic and Physical Characteristics of Rett Syndrome

March 14, 2017 updated by: Alan Percy, University of Alabama at Birmingham

Rett Syndrome Natural History: Genetic and Physical Characteristics of Rett Syndrome

Rett Syndrome (RTT) is a genetic brain disorder that occurs almost exclusively in females and is usually caused by a change (mutation) in the gene MECP2. The disorder is characterized by multiple developmental problems, as well as behavioral features, such as repetitive stereotypic hand movements, including hand washing, wringing, and tapping. While there is no cure for RTT, recent advances in the understanding of the disease suggest that the development of new, effective therapies is promising. This study will gather information on the genetic defects that cause RTT, the physical expressions of these defects, and disease progression. In turn, this may direct the development of future treatments. Expanded studies include individuals with MECP2 Duplication disorder, and RTT-related disorders including individuals with MECP2 mutations, but not meeting obligatory criteria for the diagnosis of RTT and individuals with mutations in CDKL5 and FOXG1 some of whom meet criteria for atypical RTT.

Study Overview

Status

Completed

Conditions

Detailed Description

RTT is a brain disorder that causes problems with childhood development. It is usually caused by an abnormality (mutation) in the gene MECP2. RTT can cause severe impairments in movement and communication skills, including speech and social interaction. The first signs of RTT include loss of acquired speech and loss of purposeful hand use for activities such as eating or playing. Individuals may also develop abnormal walking, repetitive hand movements, such as clapping or wringing, and abnormal breathing while awake.

Effective treatments for RTT are currently lacking. There is also inadequate information about the link between RTT clinical features and its genetic basis. In order to prepare for future clinical trials that may lead to effective therapies, it is important to collect accurate information about the characteristics of RTT and the pattern of disease progression. This study will gather historical and physical examination data to establish phenotype-genotype correlations. Data on survival and quality of life in females with RTT and males with MECP2 gene mutations will also be evaluated.

MECP2 Duplication disorder affects principally males who have one and rarely more than one additional copy of MECP2 as well as a variable number of other duplicated genes. These males have absent spoken language, shuffling gait, epilepsy, and, in some, frequent upper respiratory infections or sinusitis. Mother of these males are generally normal due to favorable skewing of X-chromosome inactivation, but in some instances may have neurodevelop-mental delays. Effective treatments are lacking. It is critical to develop phenotype-genotype correlations and longitudinal natural history data to assist the conduct of clinical trials.

RTT-related disorders feature a variety of involvements either due to MECP2, CDKL5, and FOXG1 as well as other potential causes of atypical RTT. Phenotype-genotype studies and longitudinal natural history data are essential to the conduct of future clinical trials.

Participants in this observational study will be recruited from the four sites at which the study is being conducted, as well as through the Rare Disease Clinical Research Network and the International Rett Syndrome Association (IRSA). Prior to study entry, potential participants are expected to be tested for a mutation in the MECP2 gene. No treatment will be administered at any time during this study. Study visits will occur every 6 months until the child is 6 years old and once a year thereafter. At each study visit, participants will be examined to assess physical characteristics of the disorder, such as motor behavior and disease severity. Additionally, participants will complete questionnaires about medical history, contact information, and quality of life. The first visit will last approximately 1.5 hours, and every subsequent visit will last approximately 1 hour.

Study Type

Observational

Enrollment (Actual)

10

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama at Birmingham
    • California
      • Oakland, California, United States, 94709
        • Children's Hospital of Oakland
      • San Diego, California, United States, 92123
        • University of California San Diego
    • Colorado
      • Denver, Colorado, United States, 80045-2571
        • University of Colorado Denver
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Children's Hospital Boston
    • New York
      • Rochester, New York, United States, 14627-0140
        • University of Rochester
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104-4318
        • Children's Hospital of Philadelphia
    • South Carolina
      • Greenwood, South Carolina, United States, 29646
        • Greenwood Genetic Center
    • Tennessee
      • Nashville, Tennessee, United States, 37212
        • Vanderbilt University
    • Texas
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Individuals fulfilling consensus clinical criteria for Classic or Variant Rett Syndrome, individuals with MECP2 mutations who do not meet the clinical criteria, or individuals who have a duplication of Xq28 including the MECP2 locus or individuals who have mutations in CDKL5 or FOXG1.

Description

Inclusion Criteria:

  • Meets clinical criteria for classic or variant RTT or tests positive for an MECP2 gene mutation or a MECP2 duplication or a mutation in CDKL5 or FOXG1.

Exclusion Criteria:

  • Unwilling or unable to travel to study sites for annual or biannual evaluations

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Genetic and Physical Characteristics of Rett Syndrome
Time Frame: July 31, 2019
The primary endpoint is to determine the variables related to clinical outcome in terms of genotype and phenotype. The variables include growth, head circumference, stereotypic movements, periodic breathing, epilepsy, scoliosis, and longevity. Summative data are provided by the Clinical Severity Scale (CSS) and the Motor Behavioral Assessment (MBA) and specific neurophysiologic and neuroimaging studies in selected participants.
July 31, 2019

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Genetic and Physical Characteristics of Rett syndrome
Time Frame: Through July 31, 2019
The principal secondary outcome measures include quality of life assessments of the participants (CHQ) and the principal caregiver (SF-36).
Through July 31, 2019

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Genetic and Physical Characteristics of Rett Syndrome, MECP2 Duplication disorder, and RTT-related conditions
Time Frame: July 31, 2019
No other pre-specified outcome measures are planned
July 31, 2019

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Alabama at Birmingham

Collaborators

University of Colorado, Denver
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Baylor College of Medicine
Children's Hospital of Philadelphia
University of California, San Diego
University of South Florida
Boston Children's Hospital
Rush University Medical Center
Vanderbilt University
University of Rochester
Rare Diseases Clinical Research Network
UCSF Benioff Children's Hospital Oakland
Greenwood Genetic Center

Investigators

  • Principal Investigator: Alan K Percy, MD, University of Alabama at Birmingham

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2006

Primary Completion (Actual)

October 1, 2015

Study Completion (Actual)

October 1, 2015

Study Registration Dates

First Submitted

March 3, 2006

First Submitted That Met QC Criteria

March 3, 2006

First Posted (Estimate)

March 6, 2006

Study Record Updates

Last Update Posted (Actual)

March 16, 2017

Last Update Submitted That Met QC Criteria

March 14, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RDCRN 5201
  • U54HD061222 (U.S. NIH Grant/Contract)
  • ARP 5201

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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