The neurofibromatosis (NF) syndromes are genetic conditions that result in the development of tumors on nerves.
There are three types of neurofibromatosis that are caused by different genetic changes in the body and have different types of symptoms:
- Neurofibromatosis type 1 (NF1)
- Neurofibromatosis type 2 (NF2) (also known as NF2-Related Schwannomatosis)
- Schwannomatosis
Neurofibromatosis Type 1 (NF1):
NF1 occurs in approximately 1 in every 3,000 worldwide. It is caused by mutations in the NF1 gene that codes for the protein neurofibromin. Neurofibromin is important in the signaling pathway which regulates cellular growth and development. People with NF1 have a 50 percent chance of passing it on to their children, though about half of cases occur without any family history.
People with NF1 can develop a variety of symptoms including tumors, skin changes like café au lait spots and freckling, bone-related problems like a curved spine (scoliosis) and learning challenges.
About half of people with NF1 will also develop nerve tumors called plexiform neurofibromas (PNs). While these tumors are not cancer, they can be disfiguring, painful and difficult to remove surgically. PNs can also develop into cancerous tumors, called malignant peripheral nerve sheath tumors (MPNSTs).
Before April 2020, there were no FDA-approved treatments for children with NF1 and symptomatic plexiform neurofibromas that could not be removed by surgery. Then, as a result of decades of research by the Pediatric Oncology Branch NF Team and their collaborators, selumetinib, an MEK inhibitor, was approved for children ages 2 years and older in the United States, and children ages 3 years and older in Europe with NF1 and inoperable PNs.
Neurofibromatosis Type 2 (NF2; NF2-Related Schwannomatosis)
NF2, also known as NF2-related Schwannomatosis, affects about 1 in 25,000 people worldwide and is associated with the development of bilateral vestibular schwannomas (tumors in the brain arising from the nerves important for hearing and balance), as well as other tumors, including cranial meningiomas, ependymomas, spinal tumors and intradermal schwannomas. The POB NF Team collaborates with National Institute of Neurologic Disorders (NINDS) researchers and clinicians to see people with NF2. Dr. Prashant Chittiboina in NINDS leads a natural history study for patients with NF2 that the POB team has worked on for many years.
Schwannomatosis
Schwannomatosis is the rarest form of NF and occurs in about 1 in every 40,000 people worldwide. It can be caused by mutations in different genes including LZTR1 and SMARCB1, and it leads to the development of tumors on nerves called schwannomas which often cause pain.