Genetic and Physical Characteristics of Rett Syndrome

Sponsor

University of Alabama at Birmingham (Other)

Overall Status

Completed

CT.gov ID

NCT00299312

Collaborator

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

Enrollment

Locations

115

Duration (Months)

0.9

Patients Per Site

Patients Per Site Per Month

Study Details

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	Intervention/Treatment	Phase
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 :

Mar 1, 2006

Actual Primary Completion Date :

Oct 1, 2015

Actual Study Completion Date :

Oct 1, 2015

Outcome Measures

Primary Outcome Measures

Genetic and Physical Characteristics of Rett Syndrome [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

Genetic and Physical Characteristics of Rett syndrome [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

Genetic and Physical Characteristics of Rett Syndrome, MECP2 Duplication disorder, and RTT-related conditions [July 31, 2019]
No other pre-specified outcome measures are planned

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Children's Hospital of Oakland	Oakland	California	United States	94709
3	University of California San Diego	San Diego	California	United States	92123
4	University of Colorado Denver	Denver	Colorado	United States	80045-2571
5	Rush University Medical Center	Chicago	Illinois	United States	60612
6	Children's Hospital Boston	Boston	Massachusetts	United States	02115
7	University of Rochester	Rochester	New York	United States	14627-0140
8	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104-4318
9	Greenwood Genetic Center	Greenwood	South Carolina	United States	29646
10	Vanderbilt University	Nashville	Tennessee	United States	37212
11	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
UCSF Benioff Children's Hospital Oakland
University of California, San Diego
Vanderbilt University
University of South Florida
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)