Definition

Neurofibromatosis (NF) is a disorder of the nerve fibers genetically inherited/congenital from birth. This disorder causes tumors to form on nerve fibers and can occur anywhere, including in the brain and spinal cord. Most cases of neurofibromatosis are benign, but they can become malignant.

This disorder occurs in 1 out of 3,000 births. Spontaneous mutations occur in 50% of cases, while most NF cases are due to inherited mutations. In inherited NF cases, only one parent must carry the gene mutation. NF occurrences are rare, with the age of first symptom appearance varying from birth to 30 years.

Causes

Genetic damage or mutation causes neurofibromatosis, either inherited or spontaneous. A genetic mutation is a change occurring at one or more points within the genes. Some mutations known to cause neurofibromatosis are:

• NF-1: Mutation on chromosome 17, which regulates the formation of substances that control cell growth.
• NF-2: Mutation on chromosome 22 forms a protein that cannot suppress tumor growth.
• Schwannomatosis: The gene mutation in this disorder suppresses tumor growth. In 85% of schwannomatosis cases, the mutation occurs spontaneously.

Risk factor

The biggest risk factor for developing NF is family inheritance. Genetics play a significant role in NF, with 50% of cases arising from inherited mutations within the family.

Symptoms

There are three types of neurofibromatosis, with NF-1 being more common than the other two types. About 96% of NF cases are NF type 1. Symptoms for each NF type include:

• NF-1: This tumor type causes symptoms in childhood, typically visible on the skin and bones. Usually found shortly after birth or by age 10. Other names for NF-1 include Recklinghausen disease or Von Recklinghausen. Symptoms may include:
• Flat, brown spots on the skin (café-au-lait spots): If there are more than six, the child likely has NF-1.
• Spots in the armpits or body folds.
• Small lumps on the iris of the eye: The iris is the colored part of the eye.
• Soft lumps under the skin, the size of peas. They can grow in other body parts.
• Bone deformities: Caused by abnormal bone development and mineral deficiency.
• Tumor in the optic nerve.
• Learning difficulties.
• Larger-than-average head size.
• NF-2: This tumor can cause hearing problems, ringing in the ears, and difficulty maintaining balance. Symptoms typically appear in adolescence, and the tumor grows slowly. Ear tumors can press on other nerve fibers, causing facial issues, headaches, and seizures.
• Schwannomatosis: The rarest tumor type, usually appearing between ages 25-30. Tumors develop in the head, spinal cord, and other nerve fibers. Symptoms include chronic pain, numbness or weakness in certain body parts, and muscle mass loss. Information on schwannomatosis remains limited.

Diagnosis

Doctors will first ask about family and personal health history. They will then conduct a physical exam to confirm symptoms and severity. For an NF-1 diagnosis, at least two symptoms or one symptom and a family history of NF-1 are required. Additional tests include:

• Eye examination.
• Hearing function and balance tests.
• Radiological exams like X-ray, CT scan, and MRI to detect bone abnormalities and spinal or brain tumors.
• Genetic testing, rarely performed, can be done during pregnancy. Genetic testing is 95% accurate for detecting NF-1 and 65% accurate for NF-2.

Management

Treatment techniques for managing NF-1 and NF-2 symptoms include:

• Surgery to remove tumors, though it cannot prevent new tumor growth.
• Radiation to kill tumor cells, such as those in the optic nerve.
• Therapy for NF complications, including using devices to support damaged spines or hearing aids. Brown spots do not need therapy as they are benign. Regular long-term monitoring by a neurologist is necessary for people with NF.

Complications

Complications vary by NF type. In NF-1, complications include:

• Neurological disorders, including epilepsy and hydrocephalus.
• Cosmetic issues. Café-au-lait spots can cause cosmetic concerns, especially on the face, leading to anxiety and emotional stress.
• Bone growth disorders.
• Vision problems due to optic nerve tumors.
• Hormonal changes, particularly in women, causing symptoms or worsening conditions.
• Breathing issues from tumors affecting the airways.
• Cancer. About 3-5% of NF cases can turn cancerous, including adrenal gland cancer.

In NF-2, complications include:

• Partial or total hearing loss.
• Facial nerve damage.
• Vision problems.
• Benign skin tumors.
• Benign brain tumors requiring repeated surgeries.

In schwannomatosis, chronic pain can prevent activities, needing specialized pain management by a neurologist.

Prevention

There is currently no way to prevent genetic mutations. Prevention focuses on avoiding disease complications, such as:

• Regular visits to a neurologist.
• Routine vision and hearing tests.
• Monitoring children's learning abilities and behavior.
• Early therapy to prevent permanent damage from NF.

When to see a doctor?

Emergency symptoms due to tumor growth warrant immediate medical attention. Seek medical care if experiencing:

• Sudden vision problems.
• Neurological abnormalities indicating a brain mass.
• Changes in shape or pain indicating cancer growth.
• Severe hypertension (potentially indicating a tumor in the adrenal gland).

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