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Neurofibromatosis (NF) is a rare genetic disorder caused by mutations to tumor suppressor genes. Tumor suppressor genes provide instructions that enable the body to make tumor suppressor proteins, which help regulate the growth and division of cells. When these genes do not function properly, cells can grow out of control.
In people who have NF, this unchecked cellular growth results in the formation of tumors. There are two main types of NF, as well as a third and very rare type called schwannomatosis.
Neurofibromatosis type I
Neurofibromatosis type 1 (NF1) occurs due to a mutation of the tumor suppressor gene neurofibromin 1. This mutation can occur spontaneously or can be inherited from a person’s parents.
The most common type of neurofibromatosis, NF1 can cause a wide range of symptoms that can impact skin pigmentation, the nervous system, bones, and normal development.
One of the first signs of NF1 are cafe-au-lait macules (CALMs), or cafe-au-lait spots. These are darkened areas of skin that resemble birthmarks. In some cases, they are present at birth. In other cases, they may appear during childhood or puberty. While harmless, having six or more CALMs can be a sign of NF1. Freckles in the underarms or groin are another skin pigmentation abnormality seen in people with NF1. Like CALMs, freckles are not harmful.
Neurofibromas are another common manifestation of NF1. These are benign tumors that form on the nerves. Most occur near the surface of the body and can be felt as lumps underneath the skin. Others occur deeper within the body. Neurofibromas may put pressure on nerves, causing symptoms like pain, numbness, and tingling. People with NF1 can also develop benign tumors in the eyes and along the optic nerve, which can impair vision. Plexiform neurofibromas are larger tumors that affect multiple nerves. While the majority of tumors that develop as a result of NF1 are benign, people with NF1 are at an increased risk of several types of cancer, including leukemia, brain tumors, breast cancer, malignant peripheral nerve sheath tumors, and others.
Other signs and symptoms associated with NF1 include scoliosis (lateral curvature of the spine), a larger than normal head circumference, smaller stature, bone abnormalities, early or late onset of puberty, high blood pressure, and learning disabilities.
NF1 symptoms and the severity of those symptoms can vary greatly from person to person.
Neurofibromatosis type 2
Neurofibromatosis type 2 (NF2) is caused by a mutation of the gene neurofibromin 2. As with NF1, the mutation that causes NF2 can be spontaneous or inherited. Whereas the onset of NF1 symptoms are observable at birth or during early childhood, NF2 usually has a later onset—the first symptoms typically appear during puberty or early adulthood. People with NF2 also have CALMs, but typically fewer CALMs than people with NF1.
People with NF2 develop tumors called vestibular schwannomas. These benign tumors form on one or both auditory nerves, which connect the ears to the brain. These tumors can impact the functioning of the auditory nerves, causing hearing loss, tinnitus (ringing in the ears), and problems with balance.
Tumors may also form along other nerves, which can result in a variety of neurological symptoms—impaired speech, muscle weakness, pain, numbness, facial drop, difficulty swallowing, headaches, seizures, and problems with vision, including cataracts.
Schwannomatosis
This rare type of neurofibromatosis is caused by mutations to the tumor suppressing genes SMARCB1 and LZTR1, and possibly other genetic mutations that have not yet been identified.
The benign tumors that occur with schwannomatosis are called schwannomas. These are the same type of tumor that occur with NF2. However, with schwannomatosis, these tumors do not involve the auditory nerves (at least not initially). Instead, these tumors develop on the peripheral nerves, brain, and/or along the spinal cord. Depending on the nerves that are impacted, symptoms can include chronic pain, numbness, and loss of muscle. Onset typically occurs during early adulthood.
