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Observational Study of RASopathies

This study aims to learn more about RASopathies, a group of genetic conditions like Costello Syndrome and Noonan Syndrome, which can cause developmental issues, growth problems, and an increased risk of cancer. Researchers want to understand how genes and environmental factors contribute to cancer development in people with RASopathies. The goal is to find better ways to detect or prevent these cancers and other related conditions early. You can join if you have a clinical diagnosis of a RASopathy, or if you are a family member of someone with a RASopathy. The study will collect information about your medical history and review your medical records. You will also be asked to provide blood and urine samples. Success for this study means gaining a better understanding of RASopathies, the lifetime rates of cancer development, and the clinical features of these conditions.

Study design
This is an observational study with a planned enrollment of 500 participants. It is designed to follow participants over time to understand the progression of RASopathies.
What's involved
You will complete questionnaires about your personal and family medical history. Your medical records will be reviewed, and you will provide blood and urine samples.
Compensation
Not stated in the trial record.
Follow-up
The primary endpoints, including RASopathy Syndromes, Clinical Phenotype, and Genetic and Environmental Interactions, will be measured on an ongoing basis.

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NCT04888936

Clinical, Genetic, and Epidemiologic Study of Children and Adults With RASopathies

Recruiting
Not specifiedAges 1–99Observational
National Cancer Institute (NCI)
~500 participants
Updated 2026-08-20 on ClinicalTrials.gov

At a glance

Recruiting sites
2 of 2 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
RASopathy Syndromes
Measured over ongoing
+2 more outcomes measured

Conditions

Costello Syndrome
Noonan Syndrome
Cardiofaciocutaneous Syndrome
Legius Syndrome
Capillary Arteriovenous Malformation Syndrome
RASopathy

Explore related trials

Capillary Arteriovenous Malformation SyndromeCardiofaciocutaneous SyndromeCostello SyndromeLegius SyndromeNoonan SyndromeRASopathyBRAF GeneCBL GeneDual Specificity Mitogen-Activated Protein Kinase Kinase 2GTPase KRasHRAS GeneLeucine-Rich Repeat Protein SHOC-2LZTR1 GeneMAP2K1 GeneMitogen-Activated Protein Kinase Kinase Kinase 8NRAS GenePPP1CB GenePTPN11 GeneRAF1 GeneRASA1 GeneRASA2 GeneRas-Related Protein M-RasRas-Related Protein R-RasRIT1 GeneSOS1 GeneSPRED1 Gene

Where it's being run

2 sites across 1 states
Maryland2

Study leadership

  • Douglas R Stewart, M.D. · PRINCIPAL_INVESTIGATOR · National Cancer Institute (NCI)

Who to contact

NCI Family Study Referrals
[email protected]
(800) 518-8474
Email the study team

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Do you actually qualify for this trial?

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Eligibility criteria

Inclusion

Individuals with a clinical diagnosis of a RASopathy, including Costello syndrome, Noonan syndrome, Noonan syndrome with multiple lentigines, Cardiofaciocutaneous syndrome, Legius syndrome, capillary arteriovenous malformation syndrome, or others, are eligible. Published clinical diagnostic criteria exist for most of the clinical RASopathy syndromes and differ by syndrome. It will be uncommon for individuals to have a clinical diagnosis and not have had molecular genetic testing. All individuals considered by the study team to be at risk for a RASopathy who have not had prior genetic testing will have this completed as part of the study. The rare individuals with a clinical diagnosis of a RASopathy who are not found to carry a corresponding pathogenic or likely pathogenic variant in a known RASopathy gene will be considered for exome analysis for identification of potentially novel RASopathy germline variation.
Individuals with a germline variant (P/LP or a variant of uncertain significance but predicted bioinformatically to be damaging) in a RASopathy-associated gene are eligible. These include but are not limited to: BRAF, CBL, HRAS, KRAS, LZTR1, MAP2K1,
Individuals with NF1 only are not eligible for the study. However, individuals with a dual diagnosis of both NF1 and another RASopathy (via genetic testing and/or clinical diagnosis) are eligible for the study.
All types and amounts of prior therapies are allowed.
There is no age restriction.
There is no restriction related to organ and marrow function.
Each carrier (or their appropriate surrogate if the carrier is unable) must sign an IRB-approved document of informed consent to demonstrate their understanding of the investigational nature and the risk of this study before any protocol-related studies are
All types and amounts of prior therapies are allowed.
There is no age restriction.
There is no restriction related to organ and marrow function.
Each control (or their appropriate surrogate if the control is unable) must sign an IRB-approved document of informed consent to demonstrate their understanding of the investigational nature and the risk of this study before any protocol-related studies are

Exclusion

Individuals with only a diagnosis of NF1, or a newly identified germline pathogenic germline variant in NF1, and first-degree relatives of these patients are ineligible. However, individuals with a dual diagnosis of both NF1 and another RASopathy (via genetic testing and/or clinical diagnosis) are eligible for the study.
Individuals who, in the opinion of the investigator, are not able to return for follow-up visits or obtain required follow-up studies will be excluded from participation in the NIH Clinical Center Cohort.
Individuals who, in the opinion of the investigator, are not able to return for follow-up visits or obtain required follow-up studies will be excluded from participation in the NIH Clinical Center Cohort.

What this trial measures

  • RASopathy Syndromesongoing

    To establish a longitudinal cohort of participants with a clinical diagnosis of a RASopathy and/or a pathogenic germline variation in a Ras/MAPK pathway gene (excluding NF1).

  • Clinical Phenotypeongoing

    To study the lifetime rates of cancer development in participants with a RASopathy and their unaffected family members.

  • Genetic and Environmental Interactionsongoing

    To longitudinally characterize germline RASopathy-related tumor and non-tumor clinical manifestations.