The goal of this observational study is to identify candidate biomarkers in individuals with Rett Syndrome (RTT). The main questions it aims to answer are:

• Do these biomarkers change during clinical changes in individuals with RTT?
• Are biomarkers stable over time in clinically stable individuals?
• Do these biomarkers correlate with severity of RTT?

Participants will be asked to undergo an electroencephalogram (EEG) with measurements of Evoked Potentials (EP) to measure electrical activity in the brain.

Researchers will compare findings in individuals with RTT to those in typically developing individuals to see if there are differences between the two groups.

The main goal of the project is to identify potential biomarkers that can become measures for intervention and other translational studies and, at the same time, provide insight into abnormal synaptic activity and pathogenesis of RTT. Therefore, the proposed assessments will be performed with females with RTT and age matched typically developing females. These electrophysiological assessments will be compared to established clinical outcome measures from previous work in the NIH funded Rett and Rett related disorders natural history study. The neurophysiological parameters for RTT will be correlated with each other and also to disease staging, overall clinical severity scores and through exploratory analyses with specific clinical features. The investigators will also be testing procedures to perform the recordings, electrode types and placement, and ways to reduce movement and artifact within the data to establish best practices.

Inclusion Criteria:

1. Rett Group: Females ages 3-18 (inclusive) with a clinical diagnosis of RTT with a likely pathogenic or known pathogenic variant in MECP2.
2. Likely Rett Group: Females from 1 year to < 5 years of age with MECP2 variant if regression has not yet occurred or child is within 6 months of last skill loss.
3. Typically developing (TD) Group: Females age matched to RTT population (1-18) with no developmental or cognitive concerns as assessed using the Child/Adult Behavioral Checklist, Survey of Well-Being of Young Children (<5yo), or the Wide Range Achievement Test-4 (>5 yo).

Exclusion Criteria:

Rett and Likely Rett Groups:

1. Presence of a duplication in MECP2 or any other identified pathogenic mutation in another gene.
2. Active medical conditions not typically found in RTT.

Typically Developing Group:

1. Score below norms on the performance tests
2. Have a known neurological disorder (excluding migraine)
3. Being on neuroactive medications.

Enrolled participants with Rett syndrome will include individuals receiving clinical care through the Rett Syndrome clinics at participating sites. Typically developing individuals will be recruited using study recruitment centers or family members of Rett participants at each site. Each of the sites are International Rett Syndrome Foundation Centers of Excellence (Rettsyndrome.org).

The investigators intend to submit deidentified patient data into the National Database for Autism Research (NDAR) and database of Genotypes and Phenotypes (dbGaP). Study protocols and data analysis methods will be shared through future publications.

Available data from this observational study will be released to the repository and will become available to the scientific community one year after publication of planned analyses, or after a period of 5 years from the date when the data were collected, whichever comes first.

National Institute of Mental Health (NIMH) Data Archive (NDA) policy will govern access criteria.