MedPath

RASopathy Biorepository

Recruiting
Conditions
DLG4
Costello Syndrome
GATOR-1 Gene Mutation
RAS Mutation
Cardiofaciocutaneous Syndrome
Smith-Kingsmore Syndrome
Neurofibromatosis 1
Legius Syndrome
MTOR Gene Mutation
SYNGAP1-Related Intellectual Disability
Registration Number
NCT04395495
Lead Sponsor
Children's Hospital Medical Center, Cincinnati
Brief Summary

The RASopathies are a group of developmental disorders caused by genetic changes in the genes that compose the Ras/mitogen activated protein kinase (MAPK) pathway. New RASopathies are being diagnosed frequently. This pathway is essential in the regulation of the cell cycle and the determination of cell function. Thus, appropriate function of this pathway is critical to normal development. Each syndrome in this group of disorders has unique phenotypic features, but there are many overlapping features including facial features, heart defects, cutaneous abnormalities, cognitive delays, and a predisposition to malignancies. This research study proposes to collect and store human bio-specimens from patients with suspected or diagnosed RASopathies. Once obtained, blood and/or tissue samples will be processed for: metabolic function studies, biomarkers, genetic studies, and/or the establishment of immortalized cell lines. In addition, data from the medical record (including neuropsychological evaluations) and surveys will be stored to create a longitudinal database for research conducted at CCHMC or at other research institutions.

Detailed Description

Patients who are being evaluated for a RASopathy may have overlapping features, but the disorders individually can be exceedingly rare and many are not yet well characterized. Additionally, available clinical testing is not always diagnostic in this group of patients. The investigators propose to study disorders across the RAS/MAPK pathway, identifying both commonalities and differences, under one unified ongoing research protocol. The investigators propose:

1. To investigate the metabolic and molecular basis of established and suspected RASopathies.

2. Collect specimens derived from blood, buccal cells, sputum, urine, bone marrow, tumor tissue and residual specimens, including but not limited to pleural fluid, ascetic fluid, chyle, skin, lung, lymphatic or renal tissue and/or bronchoalveolar lavage fluid, tissue specimens, and/or cells that are left over from clinical procedures from enrolled patients for research purposes only.

3. Non-invasive or minimally invasive procedures to collect tissues for research purposes only, such as saliva, skin, or blood samples are also allowed. The collection of all samples from minor subjects will be done only if it is safe for the participant. Clinical studies will take precedence over research procedures.

4. Collect demographic information, medical history, and clinical test results to create a longitudinal research database of participants with suspected or diagnosed RASopathies. Participants will also complete surveys to be included in the research database (see "Research Database" section for details).

5. Provide a facility for long-term storage of bio-specimens and clinical data from participants with suspected or diagnosed RASopathies and their unaffected relatives.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
1000
Inclusion Criteria
  • Patients with a suspected or known diagnosis of any of the group of disorders known as RASopathies (e.g., Neurofibromatosis, Costello Syndrome, Noonan Syndrome). Diagnosis may be made clinically and/or confirmed through genetic testing.
  • Unaffected relatives of patients with a suspected or known diagnosis of any of the group of disorders known as RASopathies.
Exclusion Criteria
  • Individuals who do not have a suspected or definite diagnosis of a RASopathy.
  • Individuals who do not have a relative with a suspected or definite diagnosis of a RASopathy.
  • Patients who do not have the ability/capacity to undergo the informed consent process OR whose parent/legal guardian is unable to undergo the informed consent process.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Collection of medical history50 years

Collect demographic information, medical history, and clinical test results to create a longitudinal research database of participants with suspected or diagnosed RASopathies. Participants will also complete surveys to be included in the research database (see "Research Database" section for details).

Collection of biospecimen50 years

Collect specimens derived from blood, buccal cells, sputum, urine, bone marrow, tumor tissue and residual specimens, including but not limited to pleural fluid, ascetic fluid, chyle, skin, lung, lymphatic or renal tissue and/or bronchoalveolar lavage fluid, tissue specimens, and/or cells that are left over from clinical procedures from enrolled patients for research purposes only.

Secondary Outcome Measures
NameTimeMethod
Release of Specimens and Clinical Data to Other Investigators for use in RASopathy Research50 years

Release of fresh or frozen specimens and clinical data to both CCHMC and external investigators. Applications for use of bio-specimen and/or data must be approved by the Repository Use Committee through the completion of a specimen request form. Among other data, the specimen request form will require information concerning: Principal Investigator, funding sources, a research synopsis, Institutional Review Board (IRB) approval of the research project, and details about the required samples. At the time a de-identified sample is requested, the requesting investigator may also request de-identified clinical data if needed.

Trial Locations

Locations (1)

Cincinnati Children's Hospital Medical Center

🇺🇸

Cincinnati, Ohio, United States

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