Recruiting

Observational Study

Sponsor:

Children's Hospital Medical Center, Cincinnati

Code:

NCT04395495

Conditions

RAS Mutation

Neurofibromatosis 1

Noonan Syndrome

Noonan Syndrome With Multiple Lentigines

Noonan Neurofibromatosis Syndrome

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Accepted

Study Details

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.

Conditions

RAS Mutation

Neurofibromatosis 1

Noonan Syndrome

Noonan Syndrome With Multiple Lentigines

Noonan Neurofibromatosis Syndrome

Study ID

NCT04395495

Start date

Jun 27, 2017

Status verified date

Dec, 2025

Completion date

Dec, 2065

Anticipated

Primary completion date

Dec, 2065

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Accepted

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

Enrollment

1000 participants

Anticipated

Interventions and Outcome Measures

Arms

Neurofibromatosis 1 (NF1)

Individuals with a confirmed or suspected diagnosis of Neurofibromatosis Type 1 (NF1). Diagnosis may be made clinically and/or confirmed through genetic testing. Clinical (non-genetic) diagnosis requires that individuals meet the National Institute of Health's (NIH) clinical diagnostic criteria for NF1.

Noonan Syndrome

Individuals with a confirmed or suspected diagnosis of Noonan Syndrome. Diagnosis may be made clinically and/or confirmed through genetic testing.

Noonan Syndrome with Multiple Lentigines

Individuals with a confirmed or suspected diagnosis of Noonan Syndrome with Multiple Lentigines. Diagnosis may be made clinically and/or confirmed through genetic testing.

Noonan Neurofibromatosis Syndrome

Individuals with a confirmed or suspected diagnosis of Noonan Neurofibromatosis Syndrome. Diagnosis may be made clinically and/or confirmed through genetic testing.

Cardiofaciocutaneous Syndrome

Individuals with a confirmed or suspected diagnosis of Cardiofaciocutaneous Syndrome. Diagnosis may be made clinically and/or confirmed through genetic testing.

Costello Syndrome

Individuals with a confirmed or suspected diagnosis of Costello Syndrome. Diagnosis may be made clinically and/or confirmed through genetic testing.

Legius Syndrome

Individuals with a confirmed or suspected diagnosis of Legius Syndrome. Diagnosis may be made clinically and/or confirmed through genetic testing.

Smith-Kingsmore Syndrome

Individuals with a confirmed or suspected diagnosis of Smith-Kingsmore Syndrome. Diagnosis may be made clinically and/or confirmed through genetic testing.

GATOR-1 Mutation

Individuals with a suspected or known mutation of GATOR-1.

SYNGAP1-Related Intellectual Disability

Individuals with a suspected or known mutation of SYNGAP1.

DLG4 Mutation

Individuals with a suspected or known mutation of DLG4.

MAPK1 Gene Mutation

Individuals with a suspected or known mutation of MAPK1.

MTOR Gene Mutation

1. Individuals with a suspected or known mutation of a gene associated with the MTOR cellular pathway. Diagnosis may be made clinically and/or confirmed through genetic testing.
2. Unaffected relatives of individuals with a suspected or known mutation of a gene associated with the MTOR cellular pathway.

RAS Mutation

1. Individuals with a suspected or known mutation of a gene associated with the RAS/MAPK cellular pathway. Diagnosis may be made clinically and/or confirmed through genetic testing.
2. Unaffected relatives of individuals with a suspected or known mutation of a gene associated with the RAS/MAPK cellular pathway.

Primary outcome measure

  • Collection of biospecimen [ Time Frame: 50 years ]
  • Collection of medical history [ Time Frame: 50 years ]

Central Contacts and Locations

Central contacts

Lindsey Aschbacher-Smith, MS

513-803-0077Lindsey.Aschbacher-Smith@cchmc.org

Laurie Bailey, MS

513-636-4507Laurie.Bailey@cchmc.org

Locations

Cincinnati Children's Hospital Medical Center

Recruiting

Cincinnati, Ohio, United States, 45229

Contacts

Lindsey Aschbacher-Smith, MS

513.803.0077Lindsey.Aschbacher-Smith@cchmc.org

Laurie Bailey, MS

(513) 636-4507laurie.bailey@cchmc.org

Principal Investigator:

Carlos E Prada, MD

More Information

Sponsor

Children's Hospital Medical Center, Cincinnati

Last update posted

Dec 18, 2025

Last verified

Dec, 2025

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Children's Hospital Medical Center, Cincinnati on 2025-12-18.