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Genetic and Physical Characteristics of Rett Syndrome

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ClinicalTrials.gov Identifier: NCT00299312
Recruitment Status : Completed
First Posted : March 6, 2006
Last Update Posted : March 16, 2017
Information provided by (Responsible Party):

Study Description
Brief Summary:
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.

Condition or disease
Rett Syndrome MECP2 Duplication Disorder Rett-related Disorder

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 Design

Study Type : Observational
Actual Enrollment : 10 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Rett Syndrome Natural History: Genetic and Physical Characteristics of Rett Syndrome
Study Start Date : March 2006
Primary Completion Date : October 2015
Study Completion Date : October 2015

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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).

Other Outcome Measures:
  1. 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

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00299312

United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
Children's Hospital of Oakland
Oakland, California, United States, 94709
University of California San Diego
San Diego, California, United States, 92123
United States, Colorado
University of Colorado Denver
Denver, Colorado, United States, 80045-2571
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
United States, New York
University of Rochester
Rochester, New York, United States, 14627-0140
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104-4318
United States, South Carolina
Greenwood Genetic Center
Greenwood, South Carolina, United States, 29646
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37212
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
Sponsors and Collaborators
University of Alabama at Birmingham
Rare Diseases Clinical Research Network
Greenwood Genetic Center
Baylor College of Medicine
Boston Children’s Hospital
University of Rochester
Children's Hospital of Philadelphia
University of Colorado, Denver
Rush University Medical Center
Children's Hospital & Research Center Oakland
University of California, San Diego
Vanderbilt University
University of South Florida
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Principal Investigator: Alan K Percy, MD University of Alabama at Birmingham
More Information

Additional Information:

Responsible Party: Alan Percy, Professor, Pediatrics, Neurolgy, Neurobiology, Genetics, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT00299312     History of Changes
Other Study ID Numbers: RDCRN 5201
U54HD061222 ( U.S. NIH Grant/Contract )
ARP 5201
First Posted: March 6, 2006    Key Record Dates
Last Update Posted: March 16, 2017
Last Verified: March 2017

Keywords provided by Alan Percy, University of Alabama at Birmingham:
Loss of Purposeful Hand Use Syndrome
Loss of Communication
Stereotypic Hand Movements
MECP2 mutation
MECP2 duplication
CDKL5 mutation
FOXG1 mutation

Additional relevant MeSH terms:
Mental Retardation, X-Linked
Rett Syndrome
Pathologic Processes
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System