Inclusion Criteria

-INCLUSION CRITERIA - GROUP A INDIVIDUALS:

1. Clinical diagnosis of NF1. In order to meet the diagnosis of NF1 individuals must
have 2 of the diagnostic criteria listed below:

- Six or more cafe-au-lait macules (greater than or equal to 0.5 cm in prepubertal
subjects or greater than or equal to 1.5 cm in postpubertal subjects)

- Freckling in the axilla or groin

- A tumor of the optic pathway

- Two or more Lisch nodules

- A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or
thinning of long bone cortex)

- A plexiform neurofibroma or two or more neurofibromas

- A first-degree relative with NF1 by the above criteria

We may request the medical records of potential enrollees for our review. Ideally,
individuals will have been evaluated by a geneticist and a definitive diagnosis made.
However given the unique, familial (and often unmistakable features) of NF1 it is
likely the diagnosis can be reliably made by a non-geneticist.

2. Age at study entry: 20- 50 years (inclusive)

3. Identification of a physician who will be responsible for follow-up care, if needed

4. Ability and willingness to travel to the NIH Clinical Center or University of Alabama
at Birmingham Alabama for multiple evaluations

5. Ability and willingness of both biologic parents to provide a blood (or saliva)
sample

6. Must have at least one dermal neurofibroma amenable to excisional biopsy. Preferably
the neurofibroma will be on the thorax or abdomen and be at least the size of a
pencil eraser.

INCLUSION CRITERIA - GROUP B INDIVIDUALS:

1. Biological parents (either affected or unaffected) of Group A individuals

2. Willingness to donate a blood or saliva sample for genotyping

3. Willing to undergo a brief skin and eye exam at the NIH CC (to rule out NF1) or
University of Alabama, if accompanying adult children

EXCLUSION CRITERIA - GROUP A INDIVIDUALS

MEDICAL INCLUSIONS:

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 dermal neurofibroma tumor burden or growth.

2. Patients with probable segmental or mosaic NF1 will be excluded from study
participation and medical records may be reviewed prior to enrollment for this
determination.

3. A history of administration of medications within 6 months of study entry 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.

4. Known or suspected untreated bleeding diathesis or platelet disorder that would
preclude safe and successful dermal neurofibroma and skin biopsy. Patients prescribed
aspirin or other known/suspected agent that interferes with platelet function may
also be excluded if they cannot safely discontinue its use a week ahead of the
biopsy.

5. Clinically significant unrelated systemic illness, such as serious infection,
hepatic, renal or other organ dysfunction, which in the judgment of the principal
investigator or associate investigator would compromise the patient's ability to
participate in the study procedures.

6. Inability or unwillingness to tolerate the dermal neurofibroma excision and skin
biopsy or blood draw.

VULNERABLE POPULATIONS EXCLUSIONS

1) Cognitive delay to the extent that conscious sedation is required to obtain the dermal
neurofibroma excision and skin biopsy.

OTHER EXCLUSIONS

1. Biologic parents unable or unwilling to provide a blood (or saliva) sample.

2. Inability to travel to the NIH or to The University of Alabama at Birmingham, AL

3. Individuals refusing an excisional tumor or skin biopsy.