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Genetic and Physical Characteristics of Rett Syndrome

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2014 by University of Alabama at Birmingham
Rare Diseases Clinical Research Network
University of Alabama at Birmingham
Greenwood Genetic Center
Baylor College of Medicine
Children's Hospital Boston
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
Information provided by (Responsible Party):
Alan Percy, University of Alabama at Birmingham Identifier:
First received: March 3, 2006
Last updated: December 11, 2014
Last verified: December 2014

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.

Rett Syndrome, MECP2 Duplication dIsorder, and RTT-related Conditions

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Rett Syndrome Natural History: Genetic and Physical Characteristics of Rett Syndrome

Resource links provided by NLM:

Further study details as provided by University of Alabama at Birmingham:

Primary Outcome Measures:
  • Genetic and Physical Characteristics of Rett Syndrome [ Time Frame: July 31, 2019 ] [ Designated as safety issue: No ]
    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:
  • Genetic and Physical Characteristics of Rett syndrome [ Time Frame: Through July 31, 2019 ] [ Designated as safety issue: No ]
    The principal secondary outcome measures include quality of life assessments of the participants (CHQ) and the principal caregiver (SF-36).

Other Outcome Measures:
  • Genetic and Physical Characteristics of Rett Syndrome, MECP2 Duplication disorder, and RTT-related conditions [ Time Frame: July 31, 2019 ] [ Designated as safety issue: No ]
    No other pre-specified outcome measures are planned

Estimated Enrollment: 1350
Study Start Date: March 2006
Estimated Study Completion Date: July 2019
Estimated Primary Completion Date: July 2019 (Final data collection date for primary outcome measure)
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.


Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00299312

Contact: Alan K Percy, MD 205-996-4927
Contact: Jane B Lane, RN, BSN 205-934-1130

United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Jane Lane, RN, BSN    205-934-1130   
Principal Investigator: Alan Percy, MD         
United States, California
Children's Hospital of Oakland Not yet recruiting
Oakland, California, United States
Contact: Erica Robertson    510-428-3885 ext 5458   
Principal Investigator: Mary Jones, MD         
Sub-Investigator: Audrey Brumback, MD, PhD         
University of California San Diego Not yet recruiting
San Diego, California, United States, 92123
Contact: To be named         
Principal Investigator: Jeffrey L Neul, MD, PhD         
United States, Colorado
University of Colorado Denver Not yet recruiting
Denver, Colorado, United States, 80045-2571
Contact: Victoria Allen    720-777-5590   
Principal Investigator: Tim Benke, MD, PhD         
United States, Illinois
Rush University Medical Center Not yet recruiting
Chicago, Illinois, United States
Contact: Susan Rohde    312-942-0079   
Principal Investigator: Peter Heydemann, MD         
Sub-Investigator: Elizabeth Berry-Kravis, MD         
Sub-Investigator: Colleen Buhrfiend, MD         
United States, Massachusetts
Children's Hospital Boston Recruiting
Boston, Massachusetts, United States, 02115
Contact: Katherine Barnes, BSc    617-355-8994   
Contact: Natalie Bruck    617-355-8994   
Principal Investigator: Walter E Kaufmann, MD         
United States, New York
University of Rochester Not yet recruiting
Rochester, New York, United States, 14627-0140
Contact: To be named         
Principal Investigator: Alex Paciorkowski, MD, PhD         
Sub-Investigator: Laurie Seltzer, MD         
United States, Pennsylvania
Children's Hospital of Philadelphia Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104-4318
Contact: Samantha Hagopians    215-590-5106   
Principal Investigator: Eric Marsh, MD, PhD         
United States, South Carolina
Greenwood Genetic Center Recruiting
Greenwood, South Carolina, United States, 29646
Contact: Fran Annese, LMSW    888-442-4363   
Principal Investigator: Mike Friez, PhD         
Principal Investigator: Steve A Skinner, MD         
United States, Tennessee
Vanderbilt University Not yet recruiting
Nashville, Tennessee, United States, 37212
Contact: Pranathi Matta   
Principal Investigator: Sar Peters, PhD         
Sub-Investigator: Cary Fu, MD         
United States, Texas
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Jackie Soto    832-822-1781   
Principal Investigator: Daniel G Glaze, MD         
Sub-Investigator: Bernhard Suter, MD, PhD         
Sub-Investigator: Thuy Dinh, PA         
Sponsors and Collaborators
Alan Percy
Rare Diseases Clinical Research Network
University of Alabama at Birmingham
Greenwood Genetic Center
Baylor College of Medicine
Children's Hospital Boston
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
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 Identifier: NCT00299312     History of Changes
Other Study ID Numbers: RDCRN 5201, U54HD061222, ARP 5201
Study First Received: March 3, 2006
Last Updated: December 11, 2014
Health Authority: United States: Federal Government

Keywords provided by 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
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Heredodegenerative Disorders, Nervous System
Intellectual Disability
Nervous System Diseases
Neurobehavioral Manifestations
Neurodegenerative Diseases
Neurologic Manifestations
Pathologic Processes processed this record on February 27, 2015