Natural History and Biology of Skin Neurofibromas in Neurofibromatosis Type 1
Condition: Neurofibromatosis Type 1; Neurofibroma
MeSH terms: Neurofibromatoses; Neurofibromatosis 1; Neurofibroma
Study type: Observational

Summary: 
      This study will explore the growth of dermal neurofibromas (skin tumors) in patients with
      neurofibromatosis type 1 (NF1). Investigators will try to learn: 1) how fast (or slow) these
      benign tumors grow in NF1, 2) how often new tumors appear and 3) what genes are involved in
      the growth of the tumors.

      Men and women between 20 and 50 years of age diagnosed with NF1 and their biological parents
      are eligible for this study.

      Patients with NF1 are evaluated at the NIH Clinical Center with the following tests and
      procedures:

        -  Medical examination and drawing of family tree.

        -  Photos of the back, abdomen and thigh in order to count the number of skin tumors.

        -  Photos of the skin taken with a special camera (Primos camera) that takes very detailed
           pictures of a small area of skin.

        -  Photos of the skin taken with a dermatoscope, which takes very detailed pictures of a
           small area of skin under high magnification.

        -  Biopsy of at least one skin tumor and biopsy of a small piece of normal skin.

        -  Blood sample collection for genetic testing of the gene NF1 and to establish a cell
           line.

        -  Other medical tests (e.g., x-rays or MRI) if needed.

      Patients and their families will also have a genetic counseling session and an opportunity to
      ask questions about neurofibromatosis type 1.

      Patients return to the NIH after 3, 6, 12, 18 and 24 months for follow-up photographs and
      possibly blood samples.

      Biological parents of patients provide a blood sample for genetic testing.
    

Detailed description: 
      This protocol results from a funded 2005 Bench-to-Bedside Award and explores the genetic
      basis of disease severity in neurofibromatosis type 1 (NF1) and the evaluation of three
      methods to measure disease progression of dermal neurofibromas. NF1 is a common multisystem
      genetic disorder associated with the development of benign and malignant tumors, primarily of
      the nervous system. NF1 is 100% penetrant and features variable expressivity and limited
      phenotype/genotype correlation. No standard treatment other than surgery exists for most
      NF1-associated tumors. Many aspects of the natural history of NF1-associated tumors are not
      fully characterized and require investigation to assess the effects of potential new
      treatments, in future clinical trials. The development of medical treatments for
      NF1-associated tumors is an important goal given their morbidity and the lack of non-surgical
      treatment options. The ability to predict the ultimate severity of disease would have a
      significant impact on the management and treatment of individuals with NF1.

      Sorafenib (BAY 43-9006) is a novel, orally bioavailable agent that targets downstream
      effectors in the Ras signaling pathway (a key dysregulated pathway in NF1). It has thus a
      strong scientific rationale for evaluation in NF1 related tumors. Dermal neurofibromas occur
      in nearly every individual with NF1, and are a significant cosmetic problem and a major cause
      of morbidity. This protocol will 1) quantify the growth of dermal neurofibromas in NF1 with 3
      different imaging modalities 2) use an innovative gene expression method to identify genetic
      modifiers of dermal neurofibroma burden, and 3) evaluate dermal neurofibromas and normal skin
      for the presence of targets of sorafenib. Successful validation of reliable quantitative
      imaging methods of dermal neurofibroma growth is a logical prerequisite to subsequent
      clinical trials with medical treatments, which will evaluate the effect of new agents on the
      growth rate of dermal neurofibromas. Identification of genetic modifiers may permit
      prediction of ultimate tumor burden. Evaluation of targets of new agents in dermal
      neurofibromas will allow for more rationale drug development for NF1. Given the paucity of
      protocols for adults with NF1 and dermal neurofibromas, this study will likely generate great
      interest among affected individuals and have rapid accrual.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Men and women between 20 and 50 years of age diagnosed with NF1 and their biological
        parents are eligible for this study.
      
Keywords: Tumor Imaging; NF1; Natural History; Neurofibromatosis