Neurofibromatosis, type 1 (NF1) is a genetic condition that can cause certain pigment (color) changes on the skin, an increased risk for certain types of cancer, and benign tumors in the skin, brain, and other parts of the body. The signs of NF1 can usually be found in childhood, and the first signs that are found are often the skin pigment changes, which can sometimes be very subtle. As people with NF1 get older, their chance to develop the tumors and cancer increase.
Individuals with NF1 can live normal lives, but they may develop serious health problems if they are not closely monitored by a healthcare provider who has experience with it. NF1 can potentially affect multiple body systems, and can affect individuals very differently. Individuals with NF1 are also at an increased risk to have scoliosis (curvature of the spine) or other bone abnormalities, as well as other tumors of the gastrointestinal tract or central nervous system. About half of people with NF1 also have learning disabilities.
We have over 20,000 different genes in the body. These genes are like instruction manuals for how to build a protein, and each protein has an important function that helps to keep our body working how it should. The NF1 gene makes a protein called neurofibromin. Neurofibromin works with other proteins to control how quickly the body’s cells multiply (called a tumor suppressor protein). If someone has a harmful change (called a pathogenic variant) in one of their NF1 genes, then their body does not make as much neurofibromin as it should. Without enough neurofibromin, there is not proper control over how fast our cells grow, which can lead them to multiply more cell growth than there should be. This unregulated cell growth can lead to tumors and the other signs and symptoms that we associate with NF1.
Harmful changes (called pathogenic variants) in the NF1 gene causes NF1, and are inherited in an autosomal dominant pattern, meaning that children of a carrier each have a 50% risk to inherit the pathogenic variant and associated health risks. Notably, women and men both have the NF1 genes and have the same chances to inherit and pass down mutations in these genes. Therefore, both sides of the family are important when assessing inherited risk. About 50% (or 1 in 2 people) with NF1 will also have a parent with NF1. The other 50% have no family history and will be the first ones in their family with this condition.
It is estimated that approximately 1 in 3,000 people have NF1.
Genetic testing for NF1 is not always needed, as it can be diagnosed via physical exam by a genetics specialist. There are some instances where genetic testing can be helpful:
Genetic testing for pathogenic variants in NF1 is currently available, but there are a few different ways to approach testing:
NF1 is diagnosed by detailed physical examination (usually done by a geneticist) and family history. The geneticist can look for the signs of NF1 during the examination and usually can determine if someone has NF1 or not based on that physical exam.
NF1 is suspected in a person with any of the following:
Individuals with NF1 also have an increased risk for specific types of cancer, scoliosis, and learning delays. Because the diagnosis of NF1 is made by a doctor’s exam, genetic testing for NF1 is generally not recommended.
If you or your family meet any of the above criteria, a meeting with a pediatric or adult genetics specialist can be helpful to further determine if someone has NF1.
The overall lifetime risk for cancer in NF1 is approximately 60%, which includes an increased risk for breast cancer, and certain gastrointestinal and central nervous system cancers (such as pheochromocytoma and malignant peripheral nerve sheath tumors). Studies have shown that women with NF1 have an elevated risk to develop breast cancer before the age of 50. After age 50, the risk to develop breast cancer returns to the level of other women in the general population.
Medical management for someone with NF1 and should be overseen by a medical provider who is familiar with NF1. Because NF1 affects people in very different ways, medical management should be specific to an individual’s needs. The frequency of each screening tool is tailored to an individual’s age. Some options for surveillance include:
The National Comprehensive Cancer Network (NCCN) recommends that women who have a diagnosis of NF1 should start annual mammogram screening at age 30, and should consider annual breast MRIs between the ages of 30 and 50. It is important to note the possibility that benign neurofibromas within the breast tissue may cause false-positive results on MRI. There is not currently any data or evidence to recommend risk-reducing mastectomies for women with NF1, but it may be considered on a case-by-case basis depending on family history. More personalized recommendations will take into account your personal and family history, and should be discussed with your medical provider.