Biobanking of Rett Syndrome and Related Disorders

NCT02705677 | Completed DMC

• 2 other identifiers: RDCRN # 5213U54HD061222
• Study Type: observational
• Target: 752
• Locations: 1 country
• Sites: 12

Brief Summary

The overarching purpose of this study is to advance 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. Although all these disorders are the result of specific genetic changes, there remains broad clinical variation that is not entirely accounted for by known biological factors. Additionally, clinical investigators currently do not have any biomarkers of disease status, clinical severity, or responsiveness to therapeutic intervention. To address these issues, biological materials (DNA, RNA, plasma, cell lines) will be collected from affected individuals and in some cases from unaffected family members, initial evaluation performed to identify additional biological factors contributing to disease severity, and these materials will be stored for future characterization.

Conditions

Rett Syndrome; MECP2 Duplication; CDKL5; FOXG1 Disorders

Outcome Measures

Primary Outcomes (4)

• X-chromosome inactivation in Rett syndrome (RTT)

  Characterize X-chromosome inactivation in RTT and correlate with clinical severity.

  5 years

• Bdnf polymorphisms in RTT

  Characterize Bdnf polymorphisms in RTT and correlate with clinical severity.

  5 years

• Inflammation markers in MECP2 duplication syndrome

  Evaluate inflammation markers in MECP2 duplication syndrome and correlate with disease severity.

  5 years

• Biobanking of blood for Rett syndrome (RTT), MECP2 duplication syndrome, FOXG1, CDKL5, and MECP2 mutations not producing RTT

  Blood will be collected and stored from participants with RTT, MECP2 duplication, FOXG1, CDKL5, and MECP2 mutations without RTT to analyze factors noted in Outcomes 1-3 and in secondary outcome 5 to correlate with disease severity.

  5 years

Secondary Outcomes (1)

• Breakpoints and gene content of MECP2 and FOXG1 duplications

  5 years

Study Arms (3)

Rett syndrome

This is a biobanking project for individuals with mutations in MECP2 or meeting diagnostic criteria for classic (typical) or variant (atypical) Rett syndrome in order to identify other genetic factors such as X-chromosome inactivation or genetic background that may explain the variations noted in these individuals, including those with the same MECP2 mutation. No interventions are anticipated.

MECP2 Duplication disorder

This is a biobanking project for individuals with MECP2 duplications to understand the difference in the size of the duplication and the potential impact of other genes in the duplicated segment. No interventions are anticipated.

Rett-related disorders: CDKL5, FOXG1

This is a biobanking project for individuals with mutations in MECP2, CDKL5, and FOXG1 to understand the interplay of mutations in these individuals and the resultant phenotypic expression; for example, individuals with mutations in MECP2 but not meeting diagnostic criteria for Rett syndrome or individuals with mutations in CDKL5 or FOXG1 who may or may not meet diagnostic criteria for atypical Rett syndrome. No interventions are anticipated.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Females and males of all ages must have complete testing for MECP2, FOXG1, and CDKL5 genes mutations AND must meet these requirements: Gene positive for a sequence mutation, duplication or deletion in one of these 3 genes. OR Meet consensus criteria for Rett syndrome (typical or atypical)

You may qualify if:

• Individuals of both genders and of all ages, with RTT, MECP2 Dup, and, RTT-related disorders including those with mutations or deletions in CDKL5 and FOXG1 genes, or those with RTT (atypical or typical) who are mutation negative. Additionally, unaffected family members of those people who meet the disease specific criteria stated will eligible.

You may not qualify if:

• Individuals who do not meet the above criteria will be excluded.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• National Institutes of Health (NIH): collaborator
• National Center for Advancing Translational Sciences (NCATS): collaborator
• Office of Rare Diseases (ORD): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (12)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

UCSF Benioff Children's Hospital Oakland

Oakland, California, 94709, United States

Location

University of California San Diego

San Diego, California, 92123, United States

Location

University of Colorado Denver

Denver, Colorado, 80045-2571, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

Gillette Children's Specialty Healthcare

Minneapolis, Minnesota, 55101, United States

Location

Washington University School of Medicine and St. Louis Children's Hospital

St Louis, Missouri, 63110-1093, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104-4318, United States

Location

Greenwood Genetic Center

Greenwood, South Carolina, 29646, United States

Location

Vanderbilt University

Nashville, Tennessee, 37212, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

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Related Links

• International Rett Syndrome Foundation website

Biospecimen

Retention: SAMPLES WITH DNA

DNA and RNA from blood, plasma, hair follicles, skin biopsies

MeSH Terms

Conditions

Rett Syndrome

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System

Study Officials

• Jeffrey L Neul, MD, PhD

  UCSD

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 22, 2015
• First Posted: March 10, 2016
• Study Start: September 1, 2017
• Primary Completion: July 31, 2021
• Study Completion: July 31, 2021
• Last Updated: August 5, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will share

Locations

US (12)