RAS MutationNCT04395495
RASopathy Biorepository
An observational study of RAS Mutation and Neurofibromatosis 1, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- RAS Mutation, Neurofibromatosis 1, Noonan Syndrome
- How many people
- 1,000 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Jun 2017to Dec 2065
- How long will I take part?
- 50 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: 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.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Lindsey Aschbacher-Smith, MS, 513.803.0077, Lindsey.Aschbacher-Smith@cchmc.org
Laurie Bailey, MS, (513) 636-4507, laurie.bailey@cchmc.org
About this study
Official title: Investigation Into the Natural History and Metabolic and Molecular Basis of RASopathies.
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.
Read the 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:
- To investigate the metabolic and molecular basis of established and suspected RASopathies.
- 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.
- 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.
- 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).
- Provide a facility for long-term storage of bio-specimens and clinical data from participants with suspected or diagnosed RASopathies and their unaffected relatives.
- Conditions
- RAS Mutation, Neurofibromatosis 1, Noonan Syndrome, Noonan Syndrome With Multiple Lentigines, Noonan Neurofibromatosis Syndrome, Cardiofaciocutaneous Syndrome
- Medical subject headings
- Neurofibromatosis 1, Noonan Syndrome, LEOPARD Syndrome, Neurofibromatosis-Noonan syndrome, Cardiofaciocutaneous syndrome, Costello Syndrome, Legius syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Collection of biospecimen
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.
Measured: 50 years
Collection of medical history
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).
Measured: 50 years
Secondary outcomes (1)
Release of Specimens and Clinical Data to Other Investigators for use in RASopathy Research
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.
Measured: 50 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2020
- Study start27 Jun 2017
- Primary completionDec 2065 (estimated)
- Study completionDec 2065 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (22)Papers the sponsor has linked to this study.
- Other trials for RAS MutationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,000 participants (estimated)
- Target duration
- 50 Years
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kathryn N Weaver, MD, Principal investigator, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04395495
- Sponsor's protocol ID
- 2016-7017
- Status last verified
- Dec 2025
- First submitted
- 15 May 2020
- Last updated
- 18 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Alfieri P, Piccini G, Caciolo C, Perrino F, Gambardella ML, Mallardi M, Cesarini L, Leoni C, Leone D, Fossati C, Selicorni A, Digilio MC, Tartaglia M, Mercuri E, Zampino G, Vicari S. Behavioral profile in RASopathies. Am J Med Genet A. 2014 Apr;164A(4):934-42. doi: 10.1002/ajmg.a.36374. Epub 2014 Jan 23.
PubMed 24458522Aoki Y, Niihori T, Inoue S, Matsubara Y. Recent advances in RASopathies. J Hum Genet. 2016 Jan;61(1):33-9. doi: 10.1038/jhg.2015.114. Epub 2015 Oct 8.
PubMed 26446362Baldassarre G, Mussa A, Carli D, Molinatto C, Ferrero GB. Constitutional bone impairment in Noonan syndrome. Am J Med Genet A. 2017 Mar;173(3):692-698. doi: 10.1002/ajmg.a.38086.
PubMed 28211980Cizmarova M, Hlinkova K, Bertok S, Kotnik P, Duba HC, Bertalan R, Polockova K, Kostalova L, Pribilincova Z, Hlavata A, Kovacs L, Ilencikova D. New Mutations Associated with Rasopathies in a Central European Population and Genotype-Phenotype Correlations. Ann Hum Genet. 2016 Jan;80(1):50-62. doi: 10.1111/ahg.12140. Epub 2015 Nov 26.
PubMed 26607044Conboy E, Dhamija R, Wang M, Xie J, Dyck PJ, Bridges AG, Spinner RJ, Clayton AC, Watson RE, Messiaen L, Babovic-Vuksanovic D. Paraspinal neurofibromas and hypertrophic neuropathy in Noonan syndrome with multiple lentigines. J Med Genet. 2016 Feb;53(2):123-6. doi: 10.1136/jmedgenet-2015-103177. Epub 2015 Sep 2.
PubMed 26337637da Silva FM, Jorge AA, Malaquias A, da Costa Pereira A, Yamamoto GL, Kim CA, Bertola D. Nutritional aspects of Noonan syndrome and Noonan-related disorders. Am J Med Genet A. 2016 Jun;170(6):1525-31. doi: 10.1002/ajmg.a.37639. Epub 2016 Apr 1.
PubMed 27038324Garg S, Brooks A, Burns A, Burkitt-Wright E, Kerr B, Huson S, Emsley R, Green J. Autism spectrum disorder and other neurobehavioural comorbidities in rare disorders of the Ras/MAPK pathway. Dev Med Child Neurol. 2017 May;59(5):544-549. doi: 10.1111/dmcn.13394. Epub 2017 Feb 4.
PubMed 28160302Gelb BD, Roberts AE, Tartaglia M. Cardiomyopathies in Noonan syndrome and the other RASopathies. Prog Pediatr Cardiol. 2015 Jul 1;39(1):13-19. doi: 10.1016/j.ppedcard.2015.01.002.
PubMed 26380542Groesser L, Peterhof E, Evert M, Landthaler M, Berneburg M, Hafner C. BRAF and RAS Mutations in Sporadic and Secondary Pyogenic Granuloma. J Invest Dermatol. 2016 Feb;136(2):481-6. doi: 10.1038/JID.2015.376.
PubMed 26802240Hussain MR, Baig M, Mohamoud HS, Ulhaq Z, Hoessli DC, Khogeer GS, Al-Sayed RR, Al-Aama JY. BRAF gene: From human cancers to developmental syndromes. Saudi J Biol Sci. 2015 Jul;22(4):359-73. doi: 10.1016/j.sjbs.2014.10.002. Epub 2014 Oct 23.
PubMed 26150740Jhang WK, Choi JH, Lee BH, Kim GH, Yoo HW. Cardiac Manifestations and Associations with Gene Mutations in Patients Diagnosed with RASopathies. Pediatr Cardiol. 2016 Dec;37(8):1539-1547. doi: 10.1007/s00246-016-1468-6. Epub 2016 Aug 23.
PubMed 27554254Kim EK, Choi EJ. Pathological roles of MAPK signaling pathways in human diseases. Biochim Biophys Acta. 2010 Apr;1802(4):396-405. doi: 10.1016/j.bbadis.2009.12.009. Epub 2010 Jan 14.
PubMed 20079433Kratz CP, Franke L, Peters H, Kohlschmidt N, Kazmierczak B, Finckh U, Bier A, Eichhorn B, Blank C, Kraus C, Kohlhase J, Pauli S, Wildhardt G, Kutsche K, Auber B, Christmann A, Bachmann N, Mitter D, Cremer FW, Mayer K, Daumer-Haas C, Nevinny-Stickel-Hinzpeter C, Oeffner F, Schluter G, Gencik M, Uberlacker B, Lissewski C, Schanze I, Greene MH, Spix C, Zenker M. Cancer spectrum and frequency among children with Noonan, Costello, and cardio-facio-cutaneous syndromes. Br J Cancer. 2015 Apr 14;112(8):1392-7. doi: 10.1038/bjc.2015.75. Epub 2015 Mar 5.
PubMed 25742478Myers A, Bernstein JA, Brennan ML, Curry C, Esplin ED, Fisher J, Homeyer M, Manning MA, Muller EA, Niemi AK, Seaver LH, Hintz SR, Hudgins L. Perinatal features of the RASopathies: Noonan syndrome, cardiofaciocutaneous syndrome and Costello syndrome. Am J Med Genet A. 2014 Nov;164A(11):2814-21. doi: 10.1002/ajmg.a.36737. Epub 2014 Sep 22.
PubMed 25250515Pierpont EI, Wolford M. Behavioral functioning in cardiofaciocutaneous syndrome: Risk factors and impact on parenting experience. Am J Med Genet A. 2016 Aug;170(8):1974-88. doi: 10.1002/ajmg.a.37725. Epub 2016 May 5.
PubMed 27149079
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation Into the Natural History and Metabolic and Molecular Basis of RASopathies.
- ClinicalTrials.gov ID
- NCT04395495
- Acronym / sponsor ID
- 2016-7017
- Conditions
- RAS Mutation, Neurofibromatosis 1, Noonan Syndrome, Noonan Syndrome With Multiple Lentigines, Noonan Neurofibromatosis Syndrome, Cardiofaciocutaneous Syndrome
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 1,000 participants (estimated)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Study start
- 27 Jun 2017 (actual)
- Primary completion
- Dec 2065 (estimated)
- Study completion
- Dec 2065 (estimated)
- First posted
- 20 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- To investigate the metabolic and molecular basis of established and suspected RASopathies.
- 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.
- 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.
- 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).
- Provide a facility for long-term storage of bio-specimens and clinical data from participants with suspected or diagnosed RASopathies and their unaffected relatives.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 50 Years
- Number of arms
- 14
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- 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.
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Collection of biospecimen
Time frame: 50 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.
Collection of medical history
Time frame: 50 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).
1 secondary outcome
Release of Specimens and Clinical Data to Other Investigators for use in RASopathy Research
Time frame: 50 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2025.
- Background: PubMed 24458522Alfieri P, Piccini G, Caciolo C, Perrino F, Gambardella ML, Mallardi M, Cesarini L, Leoni C, Leone D, Fossati C, Selicorni A, Digilio MC, Tartaglia M, Mercuri E, Zampino G, Vicari S. Behavioral profile in RASopathies. Am J Med Genet A. 2014 Apr;164A(4):934-42. doi: 10.1002/ajmg.a.36374. Epub 2014 Jan 23.
- Background: PubMed 26446362Aoki Y, Niihori T, Inoue S, Matsubara Y. Recent advances in RASopathies. J Hum Genet. 2016 Jan;61(1):33-9. doi: 10.1038/jhg.2015.114. Epub 2015 Oct 8.
- Background: PubMed 28211980Baldassarre G, Mussa A, Carli D, Molinatto C, Ferrero GB. Constitutional bone impairment in Noonan syndrome. Am J Med Genet A. 2017 Mar;173(3):692-698. doi: 10.1002/ajmg.a.38086.
- Background: PubMed 26607044Cizmarova M, Hlinkova K, Bertok S, Kotnik P, Duba HC, Bertalan R, Polockova K, Kostalova L, Pribilincova Z, Hlavata A, Kovacs L, Ilencikova D. New Mutations Associated with Rasopathies in a Central European Population and Genotype-Phenotype Correlations. Ann Hum Genet. 2016 Jan;80(1):50-62. doi: 10.1111/ahg.12140. Epub 2015 Nov 26.
- Background: PubMed 26337637Conboy E, Dhamija R, Wang M, Xie J, Dyck PJ, Bridges AG, Spinner RJ, Clayton AC, Watson RE, Messiaen L, Babovic-Vuksanovic D. Paraspinal neurofibromas and hypertrophic neuropathy in Noonan syndrome with multiple lentigines. J Med Genet. 2016 Feb;53(2):123-6. doi: 10.1136/jmedgenet-2015-103177. Epub 2015 Sep 2.
- Background: PubMed 27038324da Silva FM, Jorge AA, Malaquias A, da Costa Pereira A, Yamamoto GL, Kim CA, Bertola D. Nutritional aspects of Noonan syndrome and Noonan-related disorders. Am J Med Genet A. 2016 Jun;170(6):1525-31. doi: 10.1002/ajmg.a.37639. Epub 2016 Apr 1.
- Background: PubMed 28160302Garg S, Brooks A, Burns A, Burkitt-Wright E, Kerr B, Huson S, Emsley R, Green J. Autism spectrum disorder and other neurobehavioural comorbidities in rare disorders of the Ras/MAPK pathway. Dev Med Child Neurol. 2017 May;59(5):544-549. doi: 10.1111/dmcn.13394. Epub 2017 Feb 4.
- Background: PubMed 26380542Gelb BD, Roberts AE, Tartaglia M. Cardiomyopathies in Noonan syndrome and the other RASopathies. Prog Pediatr Cardiol. 2015 Jul 1;39(1):13-19. doi: 10.1016/j.ppedcard.2015.01.002.
- Background: PubMed 26802240Groesser L, Peterhof E, Evert M, Landthaler M, Berneburg M, Hafner C. BRAF and RAS Mutations in Sporadic and Secondary Pyogenic Granuloma. J Invest Dermatol. 2016 Feb;136(2):481-6. doi: 10.1038/JID.2015.376.
- Background: PubMed 26150740Hussain MR, Baig M, Mohamoud HS, Ulhaq Z, Hoessli DC, Khogeer GS, Al-Sayed RR, Al-Aama JY. BRAF gene: From human cancers to developmental syndromes. Saudi J Biol Sci. 2015 Jul;22(4):359-73. doi: 10.1016/j.sjbs.2014.10.002. Epub 2014 Oct 23.
- Background: PubMed 27554254Jhang WK, Choi JH, Lee BH, Kim GH, Yoo HW. Cardiac Manifestations and Associations with Gene Mutations in Patients Diagnosed with RASopathies. Pediatr Cardiol. 2016 Dec;37(8):1539-1547. doi: 10.1007/s00246-016-1468-6. Epub 2016 Aug 23.
- Background: PubMed 20079433Kim EK, Choi EJ. Pathological roles of MAPK signaling pathways in human diseases. Biochim Biophys Acta. 2010 Apr;1802(4):396-405. doi: 10.1016/j.bbadis.2009.12.009. Epub 2010 Jan 14.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Kathryn N Weaver, MD principal investigator
Children's Hospital Medical Center, Cincinnati
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of RAS Mutation and Neurofibromatosis 1, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lindsey Aschbacher-Smith, MS (513-803-0077, Lindsey.Aschbacher-Smith@cchmc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Collection of biospecimen (time frame: 50 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04395495, which also lists 22 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2025.