5211: Rett Syndrome, MECP2 Duplication and Rett-Related Disorders Natural History Study

The purpose of this study is to advance our 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 including the range of clinical involvement and to correlate genotype-phenotype over a broad spectrum of phenotypes.  While much has been learned about RTT, we still have to improve our understanding of the role of factors such as X chromosome inactivation, genetic background, and others including the environment, on the great variability observed even between individuals with the same MECP2 mutation.

For Diseases:

  • Rett Syndrome
  • MECP2 duplication syndrome
  • Rett related mutatons in the CDKL5 or FOXG1 genes


Rett syndrome (RS), a brain disorder affecting development in childhood, has been identified almost exclusively in females.  RS results in severe movement and communication problems following apparently normal development for the first six months of life.  The characteristic features include loss of speech and purposeful hand use, occurrence of repetitive hand movements, abnormal walking, abnormal breathing, and slowing in the rate of head growth.  Current treatment for persons with RS includes physical and occupational therapy, speech therapy, and medication for seizures. No cure for RS is known.

Recent natural history studies of RTT have taught us about the characteristics of the syndrome. However, we also learned of other similar disorders caused by abnormalities in the MECP2 gene, called MECP2 Duplication (MECP2 Dup) disorder, and of RTT-related disorders caused by changes in other genes, specifically FOXG1 and CDKL5 genes.  Furthermore, we learned that persons can have mutations in the MECP2 gene and not have RTT. Therefore, a study of the natural history of these disorders is important in order for us to learn more. 

The research questions are:

  1. Perform longitudinal and neurobehavioral assessments in people with Rett Syndrome
  2. Perform longitudinal clinical and neurobehavioral assessments and survival surveillance in MECP2 duplication syndrome.
  3. Perform longitudinal neurobehavioral assessments of individuals with CDKL5 or FOXG1 mutations. 

This is a five-year observational study that will involve the collection of information about the clinical features of RTT, MECP2 Dup, and RTT-related disorders, as well as information about quality of life. 

We plan to study a total (from all sites) of about 1500 individuals with these disorders.  The breakdown by each disorder is this: RTT: 1000, MECP2 Dup: 100, RTT-related: 100

At UAB, we hope to enroll these:  RTT or with MECP2 mutations, but not RTT: 500; MECP2 Dup: 20; RTT-related: 10.

For each visit, you will be asked to:

Participants will be examined by a physician and other study personnel, such as a dietician who will measure the size of your arm and waist, and will weigh you and measure how tall you are.  The study nurse will ask questions about what has changed with your condition since you were last seen.  You will be asked to complete questionnaires about your condition and about quality of life.  You will be asked to finish these questionnaires before coming to clinic.  These questionnaires will be sent to you ahead of time to be completed and brought to the visit.  These questionnaires should take approximately 45-60 minutes to complete.  If you are unable to read the questionnaires, they can be read to you by a family member or by study personnel. 

You will be asked to provide medical records that describe your condition, including copies of your gene testing results. 

One part of the study involves identifying and describing abnormal muscle movements that might be part of your disorder.  If abnormal movements are present, you would be videotaped or photographed during visits so that the investigator can look at it later and complete forms that are part of the study data. The images will be stored onto password-protected computers in the offices of the investigator(s) and the images will only be labeled with your ID code. 

Targeted Enrollment

To be eligible to participate, you must:

  • Be diagnosed with RTT, MECP2 Dup, and, RTT-related disorders including those with mutations or deletions in CDKL5 and FOXG1 genes,
  • Be diagnosed with RTT (atypical or typical) who are mutation negative.

You are not eligible to participate if:

  • You do not meet the above criteria.

In order to participate in a study, you must personally contact the study coordinator of the participating institution closest to you by phone or e-mail. Please use the information below to inquire about participation.


University of Alabama at Birmingham, Birmingham
Coordinator: Jane Lane, RN, BSN
Telephone: 800-822-2472, ext. 7
E-mail: jlane@uab.edu


University of California, San Diego
Contact: Karen Ditsler, MS
Telephone: 853-246-2288
E-Mail:  kditslear@ucsd.edu

UCSF Benioff Children's Hospital Oakland, Oakland
Contact: Anthony Hanna
Phone: 510-595-5458
Email: Hannaa@UCI.edu


University of Colorado, Denver
Contact: Gina VanderVeen
Phone: 720-777-5514
Email: Gina.VanderVeen@childrenscolorado.org


Rush Medical Center, Chicago
Contact: Jeremiah Furman
Phone: 312-942-2815
Email: Jeremiah_Furman@rush.edu


Boston Children's Hospital, Boston
Contact: Grace Bazin
Telephone: 617-355-5230
E-mail: Grace.Bazin@childrens.harvard.edu


Gillette Children’s Specialty Healthcare, St. Paul
Contact: Katherine Harrison, MPH, CCRC
Telephone: 651-578-5883
E-mail: KatherineAHarrison@gillettechildrens.com


Washington University School of Medicine and St. Lous Children's Hospital, St. Louis
Contact: Olga Novak
Telephone: 314-454-4267
E-mail: novako@wustl.edu


Cincinnati Children’s Hospital Medical Center
Contact: Shannon Standridge, DO
Telephone: 513-636-8016
E-mail: Shannon.Standridge@cchmc.org


Children’s Hospital of Philadelphia, Philadelphia
Contact: Casey Gorman
Telephone: 267-426-5171
Email: GormanC@email.chop.edu

Contact: Meg O'Brien
Telephone: 215-590-3057
Email: OBrienM7@email.chop.edu

South Carolina

Greenwood Genetic Center, Greenwood
Contact: Fran Annese, LMSW
Telephone: 864-941-8100
E-mail: fran@ggc.org


Vanderbilt University, Nashville
Contact:  Nicole Thompson
Phone: 615-343-4586
Email: nicole.i.thompson@vanderbilt.edu


Baylor College of Medicine, Houston
Contact: Moriah Marcogliese or Amy Hirshkowitz
Telephone: 832-822-7388
E-mail: msmarcog@texaschildrens.org or axhirshk@texaschildrens.org