This observational research study is designed to learn more about how the brain processes sound in individuals with Rett syndrome. Participants will complete a noninvasive electroencephalogram (EEG) recording while listening to simple sounds through headphones. In addition, parents or caregivers will complete questionnaires and an interview about the participant's symptoms, communication abilities, daily functioning and overall health. The information collected from this study may help researchers better understand brain activity patterns and clinical features associated with Rett syndrome and support future research efforts.

This study is an observational research project conducted under a broader IRB approved protocol that includes multiple neurodevelopmental and neurodegenerative conditions. The current ClinicalTrials.gov record describes only the Rett syndrome component of the research and reflects the procedures currently being performed for participants with Rett syndrome and age/sex-matched controls.

All participants in this study will undergo a noninvasive electroencephalogram (EEG) recording to measure brain responses to auditory stimuli. During the EEG, participants will listen to simple sounds through headphones while brain activity is recorded. No behavioral responses are required during the EEG recording.

Parents or caregivers of participants with Rett syndrome will complete questionnaires related to the participant's medical history, Rett syndrome symptoms, communication abilities, daily functioning and overall health. A structured interview may also be conducted with the parent/caregiver to assess adaptive behavior. In addition, a Rett syndrome severity scale may be completed by a clinician or trained member of the research team.

Control participants (or their parent/caregiver) will be asked to complete a demographics questionnaire.

This study does not involve assignment to a treatment or intervention, and does not involve the use of FDA regulated drugs or devices. Optional procedures described in the umbrella protocol such as Magnetic Resonance Imaging (MRI) studies are not part of the current Rett syndrome workflow and are not included in this study record.

The primary purpose of this research is to collect observational brain activity and clinical data to better characterize Rett syndrome and to support future scientific and clinical research.

Rett Syndrome Participants:

Inclusion Criteria:

• Have a clinical diagnosis of classic Rett syndrome
• Have a pathogenic MECP2 genetic variant confirmed via genetic testing
• Are past the clinical regression stage
• Are within the eligible age range for the study (2 years or older)
• Are able to tolerate the noninvasive EEG recording
• Parent or caregiver is willing and able to provide parental permission and complete questionnaires and interviews

Exclusion Criteria:

• Experiences hearing impairment or hearing loss
• Presence of medical conditions that would prevent safe participation in EEG recording
• Inability to tolerate EEG procedures
• Any condition that in the opinion of the investigator would interfere with study participation or data quality

Controls

Inclusion Criteria:

• Neurologically healthy individuals ages 2 years or older
• Are able to tolerate the noninvasive EEG recording

Exclusion Criteria:

• Experiences hearing impairment or hearing loss
• Medical history of genetic, neurological, or psychiatric disorders
• History of special education services
• Inability to tolerate EEG procedures
• Any condition that in the opinion of the investigator would interfere with study participation or data quality

The study population includes individuals diagnosed with Rett syndrome and age and sex-matched controls who are participating in an observational research study focused on brain activity and clinical characteristics. Rett syndrome participants will undergo a noninvasive EEG recording and their parent or caregiver will complete questionnaires and an interview related to symptoms, communication abilities, daily functioning and overall health. Control participants will also complete a noninvasive EEG recording and they or their parent will complete a demographics questionnaire.