Variation in Gene Expression in Neurofibromatosis Type 1

Inclusion Criteria

- INCLUSION CRITERIA:

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:

1. If female and of child-bearing age, must be willing to have a serum pregnancy test
(HCG) and

2. 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.

EXCLUSION CRITERIA:

EXCLUSION CRITERIA FOR GROUP A INDIVIDUALS INCLUDE:

1. 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.

2. 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.

3. Any history of surgery to significantly debulk spinal neurofibromas

4. 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.

5. Cognitive delay in an adult or minor to the extent that sedation is required to
obtain MRI.

6. 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.

7. Inability or unwillingness to tolerate a 1-hour (or more) MRI protocol.

8. 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.

EXCLUSION CRITERIA FOR GROUP B INDIVIDUALS INCLUDE:

1) 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.

EXCLUSION CRITERIA FOR GROUP C INDIVIDUALS INCLUDE:

1) Less than 2 years of age.

EXCLUSION CRITERIA FOR HEALTHY, NORMAL VOLUNTEERS INCLUDE:

1. 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.

2. Any history of spine surgery or significant spinal disease (severe arthritis,
autoimmune disorders, severe scoliosis, kyphosis or lordosis, cancer, NF1, NF2, or
schwannomatosis)

3. Any active spine-related complaints: e.g. persistent back pain, radicular symptoms

4. 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]).

5. Previous eye surgery of any kind.

6. Inability to provide informed consent.

7. Permanent tattooed makeup (eyeliner, lip, etc) or general tattoos. Subjects with
tattoos will be excluded if those are in a dangerous location in the body or made
with colors (e.g. dark blue and dark green) whose content in iron cannot be
definitely ruled out by the Investigators.

8. Any non-organic implant or any other device such as: cardiac pacemaker, insulin
infusion pump, implanted drug infusion device, cochlear, otologic, or ear implant,
transdermal medication patch (Nitro, hormones) that may cause problems if removed
even temporarily, any metallic implants or objects, body piercing(s), bone/joint pin,
screw, nail, plate, wire sutures or surgical staples, shunt.

9. Cerebral or other aneurysm clips.

10. Shrapnel or other metal imbedded in the subject's body (such as from war wounds or
accidents).

11. Previous work in metal fields or with machines that may have left any metallic
fragments in or near the subject's eyes.

12. A severe auto accident in the past so if it is uncertain whether any metal may still
be imbedded in the subject's body.

13. Any psychological contraindications for MRI (e.g., suffer from claustrophobia). This
will be assessed at the time when the medical history will be collected.

14. Any contraindications to having study procedures done.

15. Dental work such as crowns or bridges with indeterminate metals

16. The PI may decline to enroll a patient for other reasons.