Ground-breaking study guiding the future of Rett Syndrome Research

About the study

The Natural History Study (NHS) was a ground-breaking observational study that tracked the natural course of Rett syndrome from 2006-2021. This data is helping improve clinical trial design, uncover new insights into Rett syndrome, and raise the clinical standards of care.

Comparing the experiences of other patients can be a valuable tool in managing expectations and discussing care with providers and caregivers.

Dr. Alan Percy with patient

The leader, visionary and driver of this 15-year effort: Principal Investigator: Alan K Percy, MD University of Alabama at Birmingham

Here are a few select symptoms observed in Natural History Study:

  • Breathing

    See frequency in a day, by age and/or genetic variation, of common disordered breathing issues while awake such as hyperventilation, breath-holding or expelling air.

  • Communication

    See frequency of preserved speech and non-verbal communicative intent by age and/or genetic variation.

  • Feeding

    See degree of modified textures, prolonged mealtimes or use of gastrostomy feeding by age and/or genetic variation.

  • Hand Function

    See frequency of reaching for objects, degree of purposeful hand use, and percent-of-time in a day of hand stereotypies while awake by age and/or genetic variant.

  • Movement/Mobility

    See degree of skill including sitting, standing and walking at time of assessment by age and/or genetic variant.

  • Mood

    See degree of sustained eye contact, social interest, screaming or crying, aggression, overactivity or underactivity by age and/or genetic variant.

  • Scoliosis

    See degree of spinal curvature over time by age and/or genetic variant.

  • Seizures

    See reported seizure frequency, with or without medication, at time of assessment by age and/or genetic variant.

  • Tone

      See degree of dystonia, hypertonia/rigidity, or muscle reflexes at time of assessment by age and/or genetic variant.

Explore the Data by Symptom

Choose a variant, symptom, and age to view data comparing the experiences of over 1,000 Rett Syndrome Patients.

Explore the Data by Age Group

Choose a variant, symptom, and age to view data comparing the experiences of over 1,000 Rett Syndrome Patients.

Symptom Overview

This visualization tool offers a limited view into a subset of the NHS data collected around a sampling of common Rett syndrome symptoms. As such, it is for demonstration purposes of the much larger, more extensive, and powerful NHS data set. Outputs should serve a general purpose to guide care conversations or research inquiries, not as a predictor of phenotype for any one individual, or as a definitive portrait of all Rett syndrome symptoms.

Please refer to the Rett Syndrome Primary Care Guidelines and additional Resources for a more extensive symptom review.

Thank you to the many families who made this important research possible.

When we realized that the study was informing research into treatments/drugs to help alleviate symptoms, we were all in. Our diagnosis came in 2009. Trials then were very few and far between. Since the study, many trials are happening!- Erica, parent, California

We decided to participate in the study because we were so new to Rett Syndrome and were eager for information. The opportunity to be a part of this information gathering while also learning about it was a double benefit.- Robin, parent, New Jersey

Knowledge of natural history is essential for developing more efficient clinical trial designs. It also could help reduce the length and cost of drug development and, possibly, contribute toward greater predictability of clinical development programs.- Janet Woodcock, M.D., FDA’s Principal Deputy Commissioner

We appreciated meeting with people that understood our daughter and the challenges we face. We found a family. What an unexpected benefit from this research study!- Henry, parent, Florida

Tools and Resources

We’re here to keep you informed and empowered to get your child the best possible care and support. Explore our resources or check out what’s happening in research, and how you can get involved.

Talk to your doctor: Download the Guide

Download the Primary Care Guidelines to help facilitate discussions with your pediatrician or primary care physician.

Resources to empower you on your journey

We have articles, webinars, and educational information to learn more about symptoms, treatments, research, and care for Rett Syndrome.

Volunteer for Future Observational Studies

Participate in our upcoming observational research project to contribute important knowledge to advance treatments and care.

For Researchers and Industry

Our Rett syndrome clinical database is the most comprehensive in the world. It contains:

  • 15 years of in-person PI collected clinical data
  • 7,000+ data fields
  • 1,000+ individuals with Rett syndrome
  • Reflects participants across entire life span
  • Varying degrees of disease severity
  • Participants reflect a diversity of races, ethnicities, socio-economics and geographies

Contact us to see how this database can boost your treatment development efforts. If you are interested in using the Natural History Study data set for scientific research, contact us to get started https://www.rettsyndrome.org/contact/

Study Details:

The purpose of this study is to advance understanding of the natural history of Rett syndrome (RTT), MECP2-duplication disorder (MECP2 Dup), 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, improvements are required in understanding 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. These data will be essential to the development and conduct of clinical trials that are anticipated from ongoing studies in animal models for RTT. This study will not include clinical trials, but should set the stage for such trials and other translational research projects (e.g., development of biomarkers).

A comprehensive clinical research program will be performed including clinical, neurophysiologic, and molecular and biochemical markers across these different, but related disorders. This protocol will address the natural history components only and will serve as the basis for other study protocols including the neurophysiologic and biomarker studies. Thereby, these studies will represent a continuing pathway to focus and inform not only the ongoing but also the emerging clinical trials.