Neurofibromatosis type 1 (NF1) is a genetic condition that causes tumors to grow along nerves throughout the body. These tumors are almost always noncancerous, but NF1 affects far more than nerves alone. It can change how skin looks, how bones develop, how eyes function, and how children learn. About 1 in 3,000 people are born with the condition, making it one of the more common genetic disorders.
What Causes NF1
NF1 is caused by a change in a single gene, called the NF1 gene, which provides instructions for making a protein called neurofibromin. Neurofibromin is a tumor suppressor. It keeps cells from growing and dividing too fast by switching off a growth-promoting signal (a protein called ras). When the NF1 gene is mutated, the body produces a shortened, nonfunctional version of neurofibromin that can no longer keep that growth signal in check.
NF1 follows an autosomal dominant inheritance pattern, meaning a child only needs one copy of the mutated gene to develop the condition. A parent with NF1 has a 50% chance of passing it on with each pregnancy. However, about half of all cases arise from new, spontaneous mutations in people with no family history. The severity of NF1 varies widely, even among members of the same family who share the exact same mutation.
Skin Signs: Café-au-Lait Spots and Freckling
The earliest and most recognizable sign of NF1 is the café-au-lait spot, a flat, light-brown patch on the skin that resembles the color of coffee with milk. Many people have one or two of these spots and never have NF1. The threshold that raises suspicion is six or more spots larger than 5 mm in children under five, or larger than 15 mm after puberty. These spots are usually present at birth or appear in the first few years of life.
Freckling in unusual locations is another hallmark. Small clusters of freckles in the armpits or groin area typically show up between ages three and five and are highly suggestive of NF1 when combined with café-au-lait spots.
Types of Neurofibromas
Neurofibromas are the defining tumors of NF1, but they come in distinct forms that behave very differently.
Cutaneous neurofibromas are the most common type. They appear on or just under the skin as small, rubbery bumps that can vary in size and number. They tend to increase and multiply with age, particularly during puberty and pregnancy, likely driven by hormonal changes. While they are not dangerous, they can cause itching, tenderness, or cosmetic concerns, especially when dozens or hundreds develop over time.
Plexiform neurofibromas are less common but more serious. Rather than affecting a single small nerve, they grow along a network of nerves and can involve surrounding muscle and connective tissue. They can be present at birth, though they’re often hard to detect in young children and may not show up until imaging is done for another reason. Some plexiform neurofibromas grow large enough to distort the overlying skin and tissue, causing visible deformity. Others remain deep and are only visible on MRI, where they appear as thickened areas along nerve bundles. These tumors carry an 8% to 13% lifetime risk of transforming into a malignant peripheral nerve sheath tumor, a rare but aggressive cancer. A plexiform neurofibroma that suddenly grows rapidly, becomes painful, or changes in texture warrants prompt medical evaluation.
Eye Findings
NF1 produces two characteristic changes in the eye. Lisch nodules are tiny, raised bumps on the colored part of the eye (the iris). They are harmless and don’t affect vision, but they are extremely useful for diagnosis because they are highly specific to NF1. An ophthalmologist can spot them during a slit-lamp exam, and they become increasingly common with age.
Choroidal abnormalities, which are clusters of pigmented cells in the layer behind the retina, have been added as a diagnostic criterion for NF1 as an alternative to Lisch nodules. Research from Harvard Medical School found these abnormalities in all eyes examined from NF1 patients, highlighting how consistently they appear. Like Lisch nodules, they don’t impair vision but help confirm the diagnosis, especially in young children who haven’t yet developed other features.
A more concerning eye complication is the optic pathway glioma, a slow-growing tumor along the nerve that carries visual information from the eye to the brain. These tumors occur in about 15% of children with NF1 and are usually detected before age seven. Many never cause symptoms and simply remain stable, but some can affect vision and require treatment.
Bone and Skeletal Changes
NF1 can affect bone development in specific ways. Sphenoid wing dysplasia involves abnormal formation of a bone behind the eye socket. This can cause the eye to appear more prominent on one side and, in some cases, allows the brain’s covering to push forward into the eye socket. Imaging studies show that these bone changes can be progressive, worsening over time as nearby plexiform neurofibromas grow into and remodel the bone.
Tibial dysplasia affects the shinbone, causing it to bow or thin. This typically appears in infancy or early childhood, and the weakened bone can fracture and struggle to heal properly. Scoliosis (curvature of the spine) is also more common in children with NF1 than in the general population, and some cases progress enough to need bracing or surgery.
Learning and Attention Challenges
Cognitive effects are among the most common and underrecognized features of NF1. In one study, 52% of children with NF1 experienced academic underachievement, a rate 3.5 times higher than a control group. About 20% had a specific learning disability in reading, spelling, or math. Of those with academic difficulties, roughly one-third had a general learning disability tied to lower IQ scores.
ADHD is particularly prevalent. In the same study, 38% of children with NF1 met criteria for ADHD, compared to 12% of controls. Even children with NF1 who didn’t have a formal learning disability still showed subtle difficulties with sustained attention and visuospatial skills, the ability to understand and mentally manipulate shapes and spatial relationships. These cognitive effects can appear before any physical signs of NF1 become prominent, so awareness is important for getting children the right educational support early.
How NF1 Is Diagnosed
Diagnosis is clinical, meaning it’s based on observable features rather than a single test. The revised diagnostic criteria require two or more of the following: six or more café-au-lait spots of the appropriate size, freckling in the armpits or groin, two or more neurofibromas or one plexiform neurofibroma, an optic pathway glioma, two or more Lisch nodules or choroidal abnormalities, a distinctive bone abnormality like sphenoid dysplasia or tibial bowing, or a parent with NF1.
Genetic testing can confirm the diagnosis by identifying a mutation in the NF1 gene, and it’s especially useful when a child is too young to have developed enough visible features. Testing picks up the mutation in about 95% of people who have NF1.
Treatment Options
There is no cure for NF1, but individual features can be managed. Small cutaneous neurofibromas that cause discomfort or cosmetic concerns can be surgically removed, though new ones may continue to appear. Plexiform neurofibromas are harder to treat surgically because they wrap around nerves and blend into surrounding tissue, making complete removal difficult without damaging healthy structures.
For symptomatic, inoperable plexiform neurofibromas, the FDA has approved a medication (sold as Koselugo) for patients one year of age and older. This drug works by blocking the overactive growth signaling pathway that drives tumor growth when neurofibromin is missing. In clinical trials, it shrank tumors in a meaningful percentage of patients and reduced pain and functional limitations. The medication is taken as a capsule twice daily, and patients are monitored regularly for side effects including skin changes, digestive issues, and effects on heart function.
Beyond tumor-specific treatment, managing NF1 involves regular monitoring: annual skin exams to track neurofibromas, periodic eye exams to check for optic gliomas and Lisch nodules, developmental assessments for children, and orthopedic evaluations when bone abnormalities are present. The unpredictability of NF1 means that ongoing surveillance is a core part of care throughout life.