Rapid NF1-PN growth and symptom progression are typical during early childhood, but disease progression can occur at any time.

Neurofibromatosis type 1 (NF1) is a genetic condition that causes changes in skin pigmentation and the development of tumors along the nerves in the skin, brain, and spinal cord. Among these, NF1-associated plexiform neurofibromas (NF1-PN) are common, affecting up to 50% of people with NF1.

PN are benign tumors that develop within the sheath of nerve cells in the peripheral nervous system. They can cause various complications, including:

  • pain
  • movement problems
  • bowel and bladder dysfunction
  • vision problems
  • cosmetic concerns

These tumors — and the complications they can cause — may change over time. This article discusses the potential ways NF1-PN and its symptoms may progress and how understanding these changes may help with improved management and treatment.

The progression of NF1-PN varies not only from person to person but also from tumor to tumor within a single individual.

NF1-PN generally develops at birth or in early childhood, growing most rapidly before 5 years of age. During the early years, NF1-PN typically progresses at the fastest rate, with tumors potentially increasing in volume by 20% to 240% per year.

As people age, NF1-PN tumor growth usually slows. In adulthood, tumor growth greater than 20% is uncommon, and available data suggests that most increase in size by less than 5% annually.

Not all tumors increase in size over time, though, and shrinkage of NF1-PN tumors can also occur. Tumor shrinkage is most common in adults but has also been observed in children and adolescents.

In a 2020 study involving 26 adults with NF1-PN, 39% of people experienced tumor shrinkage during the study. Among the 186 tumors collectively analyzed, approximately 3 in 5 decreased in size by a median of 59% over the course of 9 years.

However, another study from 2020 involving younger participants found a lower rate of spontaneous tumor shrinkage, with only 8.8% of tumors shrinking over up to 7 years of follow-up.

In most cases, NF1-PN tumors remain benign (noncancerous). However, in 8% to 13% of cases, tumors can become malignant, leading to additional complications and health concerns.

People with NF1-PN may experience various symptoms depending on how the tumors affect their nerves. These symptoms may change over time as tumors grow or shrink.

A 2018 review involving 41 people with NF1-PN looked at how the symptoms associated with these tumors change over time. Over approximately 6.5 years, more people reported symptoms related to pain, motor dysfunction, and bladder and bowel problems. People with existing breathing issues also reported worsening symptoms over time.

Worsening of symptoms was most likely to occur in people whose NF1-PN tumors grew. Among people whose tumors did not substantially change in size throughout the study, some experienced worsening symptoms. However, one person also reported an improvement in symptoms after 13 years of follow-up.

There is currently no cure for NF1-PN, but there are some measures to help slow its progression.

For many years, one of the main options available to relieve symptoms related to NF1-PN and prevent worsening symptoms was surgically removing tumors. However, 2022 research suggests that approximately 1 in 3 people with NF1-PN are not suitable candidates for surgery, which historically resulted in limited options.

In recent years, targeted therapies called MEK inhibitors have shown promise in the treatment of NF1-PN.

Research involving 50 children with NF1-PN found that two-thirds experienced a reduction in tumor size using the MEK inhibitor selumetinib that lasted, on average, at least 12 months. Selumetinib received approval in 2020 for the treatment of NF1-PN in children at least 2 years of age.

In another study involving 25 children with NF1-PN, 72% experienced any tumor shrinkage with selumetinib treatment, and 68% had a response lasting at least 1 year. Notably, 11 participants had progressive disease at baseline, suggesting that treatment both stopped and reversed the progression of NF1-PN.

Additionally, participants with PN-associated pain at the start of the study experienced decreased pain intensity throughout the treatment, with pain relief reported as early as 3 months.

Other medications and interventions can also help relieve symptoms related to NF1-PN. Sometimes, doctors may also consider chemotherapy, particularly for the treatment of tumors in the brain or optic nerve.

People living with NF1-PN and their loved ones can work closely with their care team to monitor the progression of the disease and its associated symptoms. A person should report any changes in their symptoms so that healthcare professionals can take the appropriate steps to help slow, reverse, or adapt to the disease’s progression.

Even in the absence of symptoms, routine monitoring can help detect changes in tumor burden that may contribute to symptoms in the future. Early detection and intervention typically help improve the likelihood of treatment success and the prevention of disease progression.

The clinical progression of NF1-PN is highly variable both between and within people. In general, rapid tumor growth and progression of symptoms are observed during the early childhood years, but disease progression can occur at any time. Spontaneous shrinkage of tumors can also occur, though it is less common.

Treatment options — including medication and surgery — are available to help slow or reverse the progression of NF1-PN. By working closely with their healthcare teams, people with NF1-PN can detect changes in their condition more quickly and initiate care that may help relieve or prevent worsening symptoms.