Doctor talks with female patient about neurofibromatosis

The term “neurofibromatosis” refers to a group of genetic conditions that cause tumors to develop on nerve tissues throughout the body, including the brain and spinal cord. The conditions arise from genetic mutations that lead to rapid cell growth and division, resulting in the formation of tumors (neurofibromas). Although neurofibromas are usually small and benign, they can sometimes cause disruptive symptoms and complications. Additionally, though rare, a tumor can potentially progress and become cancerous.

The types of neurofibromatosis include neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and schwannomatosis.

Neurofibromatosis type 1

Symptoms of the condition now known as NF1 were described by medical practitioners as early as the 13th century. In 1882, a German physician named Friedrich von Recklinghausen coined the term “neurofibromatosis” after accurately describing the condition in terms of how the affected tissues and cells look under a microscope. For this reason, NF1 is also known as von Recklinghausen’s disease.

NF1 is relatively rare, affecting an estimated 1 in 3,000 Americans. However, according to the National Cancer Institute (NCI), it is the most common type of neurofibromatosis as well as the most common cancer predisposition syndrome. This means patients who are diagnosed with NF1 have a heightened risk of developing cancer at some point during their life.

Neurofibromatosis type 1 causes

NF1 results from mutations in the NF1 gene on chromosome 17. The NF1 gene provides instructions for neurofibromin, a tumor suppressor protein that plays a crucial role in regulating cell growth and division. A mutation in the NF1 gene can compromise the function of neurofibromin, which can lead to uncontrolled cell proliferation and the formation of neurofibromas.

The causes of the gene mutations that lead to the development of NF1 are unknown.

Neurofibromatosis type 1 risk factors

Most NF1 cases are acquired rather than inherited. Acquired gene mutations occur in one cell and then are passed on to any new cells that form from the mutated cell. An acquired mutation cannot be passed on to children because it does not affect sperm or egg cells.

With that said, individuals who have a family history of NF1 are at risk of inheriting the mutated gene. This highlights the genetic complexities associated with the condition.

Neurofibromatosis type 1 symptoms

Neurofibromas caused by NF1 may be noticeable on and underneath the skin, usually during childhood. The tumors are generally painless and may feel like soft, rubbery nodules. They may grow individually, in small clusters or throughout the body. NF1 is also associated with pigmented birthmarks known as café-au-lait skin spots. Additionally, older children, teenagers and adults may develop freckles in their underarm and groin areas.

In about 30% of NF1 cases, plexiform neurofibromas develop in the patient’s facial and skull region, usually early in life. Though initially benign, plexiform neurofibromas often transform into malignant peripheral nerve sheath tumors (MPNSTs), which are aggressive cancerous tumors that can be challenging to treat. The NCI estimates that approximately 15% of patients with plexiform neurofibromas will ultimately develop MPNST.

Neurofibromatosis type 1 treatment

Because there is currently no cure for the underlying gene mutation, NF1 treatment focuses on addressing the symptoms and complications. Various medical specialists work together to create a tailored treatment plan to meet the unique needs of each patient. This may involve regular monitoring and surveillance to track the development of neurofibromas and assess their impact on surrounding tissues. If a tumor is causing pain, compressing vital structures or creating cosmetic concerns, surgical removal may be considered.

Neurofibromatosis type 2

Unlike the more common NF1, NF2 causes benign tumors known as acoustic neuromas to develop on the main nerve leading from the inner ear to the brain. NF2 tumors can also grow on spinal nerves.

According to the NCI, the incidence of NF2 is approximately 1 in 25,000 to 40,000 individuals in the United States.

Neurofibromatosis type 2 causes

NF2 is caused by mutations in the NF2 gene on chromosome 22. NF2 provides instructions for merlin, a tumor suppressor protein that is vital in regulating cell growth. A mutation in the NF2 gene can compromise the function of merlin, which can lead to uncontrolled cell division and the formation of acoustic neuromas, which are also known as bilateral vestibular schwannomas. The hallmark sign of NF2, acoustic neuromas can affect the nerves that control hearing and balance.

The causes of the gene mutations that lead to the development of NF2 are unknown.

Neurofibromatosis type 2 risk factors

Like NF1, NF2 often arises spontaneously rather than being inherited, with the majority of cases resulting from new mutations in the NF2 gene. Individuals who have a family history of NF2 are at increased risk of inheriting the mutated gene.

No environmental or lifestyle factors are known to contribute to the development of NF2. With early detection and genetic counseling, it may be possible to manage the potential risk and impact of this rare genetic condition, which underscores the importance of a proactive and informed approach.

Neurofibromatosis type 2 symptoms

NF2 can cause distinctive symptoms that are primarily related to the growth of tumors on the nerves responsible for hearing and balance. These include progressive hearing loss, dizziness and impaired balance. As an acoustic neuroma grows, it may begin to affect the facial nerves, causing facial weakness or numbness. Additionally, NF2 can cause other nervous system complications, such as spinal cord tumors and meningiomas.

Neurofibromatosis type 2 treatment

NF2 treatment requires a comprehensive, multidisciplinary approach aimed at addressing the specific symptoms and enhancing the patient’s overall quality of life. When planning treatment, key considerations include the location and size of the tumors and their impact on neurological functions. Surgical removal of a tumor may be considered to address complications, such as hearing loss or facial weakness. Other options for managing tumor growth and the associated symptoms include radiation therapy and medication. Finally, regular monitoring and ongoing care by a team of specialists are essential components of an NF2 treatment strategy.

NF1 vs. NF2

Other than the physical locations of the neurofibromas associated with NF1 and NF2, the most significant difference between these two types of neurofibromatosis is the risk of developing cancer. Researchers have linked NF1 to several types of cancer, including ovarian cancer, melanoma and sarcoma. The results of recent studies suggest that people with NF1 are almost 10 times more likely than the general population to develop some form of cancer during their lifetime.

On the other hand, according to the American Society of Clinical Oncologists, the lifetime risk of cancer development in an individual with NF2 is relatively low.

Another notable difference between NF1 and NF2 is the age at the time of diagnosis. NF1 symptoms are often apparent at birth and during early childhood, while NF2 symptoms tend to become noticeable during the late teens or early 20s. In some cases, NF2 is diagnosed after age 40.

Schwannomatosis

Schwannomatosis is a rare neurological condition characterized by the development of schwannomas, a type of neurofibroma that arises in the Schwann cells that wrap around and protect nerve fibers. Unlike NF1 and NF2, schwannomatosis cannot progress into cancer.

Schwannomatosis causes

The precise causes of schwannomatosis are not yet fully understood. Unlike NF1 and NF2, schwannomatosis does not result from mutations in the NF1 or NF2 genes. Research suggests that the condition may be associated with alterations in other yet unidentified genes related to Schwann cell function or nerve development.

Schwannomatosis typically occurs sporadically without a clear pattern of inheritance. The complex genetic underpinnings of schwannomatosis are an active area of investigation, with ongoing research aimed at unraveling the specific genetic factors contributing to the development of this rare neurological disorder.

Schwannomatosis risk factors

Schwannomatosis is a rare condition, and its risk factors are not well-defined. While there are instances of familial cases, the specific genetic factors that contribute to the development of schwannomatosis are not fully understood.

Schwannomatosis symptoms

The most common symptom of schwannomatosis is chronic pain stemming from the affected nerve or tumor. Some patients also experience sensory disturbances, such as numbness, tingling sensations and muscle weakness. Unlike NF2, schwannomatosis does not cause hearing- or balance-related symptoms.

Schwannomatosis treatment

Pain management is a key aspect of schwannomatosis treatment. This may involve medications, physical therapy or other interventions. Ongoing monitoring and follow-up care are essential to track the progression of the symptoms and adjust the treatment plan as needed.

If a tumor is causing disruptive symptoms or compressing nearby structures, surgical removal may be considered. However, due to the complexities and risks associated with neurofibromatosis surgery, the decision must be made on a case-by-case basis.

Benefit from world-class care at Moffitt Cancer Center

All types of neurofibromatosis are complex and uncommon. Therefore, it is essential to seek care from an experienced specialist. Moffitt is a high-volume cancer center, and the multispecialty team in our Neuro-Oncology Program has opportunities to diagnose and treat all types of neurological conditions, including NF1, NF2 and schwannomatosis.

At Moffitt, we take an individualized, patient-first approach to neurofibromatosis treatment, which can range from dietary and behavioral counseling to radiation therapy or chemotherapy for cancer. Additionally, our patients have access to groundbreaking cancer therapies and can participate in clinical trials that are not available elsewhere.

Moffitt provides every new patient with rapid access to a cancer expert. You can request an appointment with a specialist in our Neuro-Oncology Program by calling 1-888-663-3488 or submitting a new patient registration form online. We do not require referrals.