Study of Disease Severity in Adults With Neurofibromatosis Type 1 (NF1)

NCT00111384 | Completed

• 2 other identifiers: 05015205-C-0152
• Study Type: observational
• Target: 313
• Locations: 1 country
• Sites: 1

Brief Summary

This study may identify genes that predict the seriousness of neurofibromatosis type 1 (NF1). Finding these genes may explain why some people with NF1 have more medical problems than others. The study will also examine medical problems in NF1 that are rarely seen and are not well understood. Male and female patients with NF1 who have gone through puberty may be eligible for this study, as well as patients of any age who have unique or under-recognized disease features. Affected and unaffected family members, including parents, siblings, and more distant relatives, may also be enrolled. Candidates are screened with a discussion of medical history or review of medical records, or both. Participants undergo the following procedures: Patients with NF1

• Physical examination and family history
• Photographs of the iris of each eye
• Photographs of the back, abdomen and thigh to count skin tumors
• Photographs of the face and body (with underwear on) to help track growth and appearance
• Magnetic resonance imaging (MRI) of the spine (This test uses a magnetic field and radio waves to look for tumors and curvature of the spine. The patient lies still in the scanner, a narrow cylindrical device, wearing earplugs to muffle loud knocking sounds that occur during the scan. A contrast material called gadolinium is injected into a vein through a catheter to enhance the images.)
• Blood draw for genetic studies
• Possibly a skin biopsy (with the use of numbing medicine, removal of a small sample of skin tissue) to grow cells in the laboratory Patients with NF1 who have unique or under-recognized disease features
• Physical examination and family history
• Blood draw for genetic studies
• Possibly a skin biopsy
• Possibly additional tests, such as blood work, x-rays, photographs, MRIs, ultrasounds, or other tests Unaffected family members
• Blood draw for genetic studies
• Brief skin and eye examinations
• Possibly a skin biopsy for cell culture Families are asked to give permission for researchers to recontact them for follow-up information, additional blood samples, or follow-up visit.

Conditions

Legius Syndrome; Neurofibromatosis Type 1

Keywords

Phenotype; NF1-associated tumors; NF1; EQTL; Modifier Genes; Natural History; Neurofibroma; Neurofibromatosis Type 1

Outcome Measures

Primary Outcomes (3)

• Phenotype individuals and family members affected with NFl by routine history and physical.

  Phenotype severityPhenotype individuals and family members affected with NF1 by routine history and physical. The primary (spinal neurofibroma burden) and secondary (dermal neurofibroma burden, head circumference, number of Lisch nodules, scoliosis, history of plexiform neurofibromas, height) sub- phenotypes will be quantified with as appropriate technology (MRI, iris exam and photography, physical exam, medical history).

  ongoing

• Identify candidate modifier genes by determining the correlation coefficient of the level of gene expression and the severity of each sub- phenotype (as phenotyped in Aim 1).

  Identify candidate modifier genes by determining the correlation coefficient of the level of gene expression and the severity of each sub- phenotype (as phenotyped in Aim 1).

  ongoing

• Characterize individuals with 1) unique or under-recognized features of NFl, and 2) individuals with NFl-like phenotypes, including those patients with a known or suspected RAS pathway disorder.

  Characterize individuals with 1) unique or under-recognized features of NFl, and 2) individuals with NFl-like phenotypes, including those patients with a known or suspected RAS pathway disorder.

  ongoing

Study Arms (2)

Group A

Affected participants, must have a correct clinical diagnosis of NF1.

Group B

Unaffected individuals greater than 2 years of age who are relatives of participants.

Eligibility Criteria

• Age: 2 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals with the genetic disorder Neurofibromatosis Type 1

You may qualify if:

• Group A: All affected individuals in a family who are post-pubertal male and female individuals and who meet the 1988 NIH criteria for neurofibromatosis type 1 (NIH Consensus Development Conference 1988).
• Group B: Unaffected individuals greater than 2 years of age who are relatives of participants (especially parents, but also siblings) are eligible to enroll and are critical to the success of the study. These individuals may be of any gender and ethnicity. If the individual is pre-pubertal, s/he must have a brief evaluation at the NIH Clinical Center (abbreviated medical history and skin and eye exam) to ensure s/he is not affected with NF1.
• Group C: individuals with unique or under-recognized features of NF1 of any age, gender or ethnicity and must have a correct clinical diagnosis of NF1 (NIH Consensus Development Conference 1988). all Group C participants enrolling in the study identify a physician who will be responsible for follow-up care so this can be arranged (if needed) at the conclusion of the evaluation at NIH.
• For healthy normal volunteers used for MRI imaging of the spine, we will aim to recruit one male and one female from each of 5 decades (18-30 years, 31-40 years, 41-50 years, 51-60 years, 61-70 years). These individuals may be of any ethnicity.
• Additional requirements include:
• If female and of child-bearing age, must be willing to have a serum pregnancy test (HCG) and
• Willingness to undergo a brief, focused history and physical exam to rule out occult spine pathology and to verify there are no contra-indications to spinal MRI imaging.

You may not qualify if:

• Any history of administration (or current use) of radiation therapy, chemotherapeutic agents or biologic agents (experimental or not) that resulted in a documented significant change in spinal neurofibroma tumor burden or growth.
• Any history of administration (or current use) of medication that might reasonably be expected to alter the natural history of tumor growth (examples include pirfenidone, interferon, farnesyl transferase inhibitor (FTI), MTX/VBL, thalidomide, growth hormone) or cause significant changes in gene expression profile.
• Any history of surgery to significantly debulk spinal neurofibromas
• Pregnancy/Lactation. If an affected pregnant or lactating woman is eligible for participation, we will request that she enroll after the conclusion of the pregnancy or lactation.
• Cognitive delay in an adult or minor to the extent that sedation is required to obtain MRI.
• Presence or suspected presence of hardware (Harrington rods) or metallic objects (e.g. shrapnel, aneurysm clips) or history of exposure to such objects (e.g. welding) that preclude MRI imaging.
• Inability or unwillingness to tolerate a 1-hour (or more) MRI protocol.
• Patients will be excluded if they cannot travel to the NIH because of their medical condition OR are less than 2 years of age. The PI may decline to enroll a patient for other reasons.
• \) A non-affected pregnant or lactating woman in a family for whom LCL immortalization will not be performed may participate. However, if she is a member of a multi-affected family (and thus her blood will be used to prepare LCLs) we will request that she donate a blood sample at the conclusion of her pregnancy or upon the weaning of her child.
• \) Less than 2 years of age.
• Pregnancy or lactation (a serum HCG level will be drawn on all child-bearing age women). Women unwilling to have a serum pregnancy test cannot participate.
• Any history of spine surgery or significant spinal disease (severe arthritis, autoimmune disorders, severe scoliosis, kyphosis or lordosis, cancer, NF1, NF2, or schwannomatosis)
• Any active spine-related complaints: e.g. persistent back pain, radicular symptoms
• Clinically significant medical condition that, in the opinion of the investigator, would compromise the patient's safety or affect his/her MRI (e.g., diabetes mellitus, chronic hypertension, severe anemia, kidney disease, heart disease \[angina, arrhythmias, congestive heart failure\]).
• Previous eye surgery of any kind.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Pemov A, Park C, Reilly KM, Stewart DR. Evidence of perturbations of cell cycle and DNA repair pathways as a consequence of human and murine NF1-haploinsufficiency. BMC Genomics. 2010 Mar 22;11:194. doi: 10.1186/1471-2164-11-194.

  PMID: 20307317 BACKGROUND

• Stewart DR, Brems H, Gomes AG, Ruppert SL, Callens T, Williams J, Claes K, Bober MB, Hachen R, Kaban LB, Li H, Lin A, McDonald M, Melancon S, Ortenberg J, Radtke HB, Samson I, Saul RA, Shen J, Siqveland E, Toler TL, van Maarle M, Wallace M, Williams M, Legius E, Messiaen L. Jaffe-Campanacci syndrome, revisited: detailed clinical and molecular analyses determine whether patients have neurofibromatosis type 1, coincidental manifestations, or a distinct disorder. Genet Med. 2014 Jun;16(6):448-59. doi: 10.1038/gim.2013.163. Epub 2013 Nov 14.

  PMID: 24232412 BACKGROUND

• Brems H, Park C, Maertens O, Pemov A, Messiaen L, Upadhyaya M, Claes K, Beert E, Peeters K, Mautner V, Sloan JL, Yao L, Lee CC, Sciot R, De Smet L, Legius E, Stewart DR. Glomus tumors in neurofibromatosis type 1: genetic, functional, and clinical evidence of a novel association. Cancer Res. 2009 Sep 15;69(18):7393-401. doi: 10.1158/0008-5472.CAN-09-1752. Epub 2009 Sep 8.

  PMID: 19738042 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Neurofibromatosis 1; Legius syndrome; Neurofibroma

Condition Hierarchy (Ancestors)

Neurofibromatoses; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Peripheral Nervous System Neoplasms; Nervous System Neoplasms

Study Officials

• Douglas R Stewart, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2005
• First Posted: May 20, 2005
• Study Start: July 27, 2005
• Last Updated: May 1, 2026

Record last verified: 2026-04-13

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: At the time of a request and as long as needed.
• Access Criteria: De-identified clinical data will be shared with collaborators under appropriate agreements.

Locations

US (1)