Neurofibromatosis

Neurofibromatosis
Neurofibromatosis.jpg
Back of an elderly woman with neurofibromatosis type 1
Specialty	Neurosurgery, Genetics
Symptoms	Skin lumps, scoliosis, hearing loss, vision loss
Complications	Tumor growth, neurological issues, learning disabilities
Usual onset	Birth to early adulthood
Duration	Lifelong
Types	Neurofibromatosis type 1 (NF1), Neurofibromatosis type 2 (NF2), Schwannomatosis
Causes	Genetic mutation (inherited or spontaneous)
Diagnosis	Clinical symptoms, genetic testing, imaging studies
Treatment	Surgery, radiation therapy, chemotherapy, cochlear implants
Prognosis	NF1: normal life expectancy NF2: shortened life expectancy
Frequency	1 in 3,000 people (United States)

Neurofibromatosis (NF) is a group of genetic disorders that cause the growth of tumors in the nervous system. It includes three distinct conditions:

• Neurofibromatosis type 1 (NF1) – More common, involves skin changes and nerve tumors.
• Neurofibromatosis type 2 (NF2) – Characterized by tumors affecting the auditory nerves, leading to hearing loss.
• Schwannomatosis – Causes painful nerve tumors but does not typically affect hearing.

The tumors in neurofibromatosis are generally benign (non-cancerous), but they can sometimes become malignant.

Signs and Symptoms

The symptoms vary depending on the type of neurofibromatosis and may include:

Neurofibromatosis Type 1 (NF1)

• Skin changes – Café au lait spots, freckling in the underarms or groin.
• Nerve tumors – Neurofibromas, which can appear under the skin or deeper in the body.
• Bone abnormalities – Scoliosis (curved spine) or abnormal bone development.
• Learning disabilities – Mild intellectual disability or attention deficit issues.
• Eye involvement – Lisch nodules (tiny brown spots on the iris), optic gliomas (tumors affecting vision).

Neurofibromatosis Type 2 (NF2)

• Hearing loss – Due to bilateral vestibular schwannomas (tumors on the auditory nerves).
• Balance issues – Difficulty with coordination and dizziness.
• Vision problems – Early cataracts and other eye issues.
• Facial weakness or numbness – Due to tumors affecting cranial nerves.

Schwannomatosis

• Chronic pain – Often the first symptom.
• Multiple schwannomas – Benign tumors along nerves, but without affecting hearing.
• Nerve compression symptoms – Tingling, weakness, or numbness in affected areas.

Causes and Genetics

Neurofibromatosis is genetic, caused by mutations in different genes:

• NF1 – Mutation in the NF1 gene on chromosome 17, affecting neurofibromin, a tumor suppressor.
• NF2 – Mutation in the NF2 gene on chromosome 22, affecting merlin, another tumor suppressor.
• Schwannomatosis – Mutations in the SMARCB1 or LZTR1 genes, also on chromosome 22.

NF is an autosomal dominant disorder, meaning only one parent needs to have the mutation for a child to inherit it. However, about 50% of cases arise from a spontaneous mutation, with no family history.

Diagnosis

The diagnosis is based on:

• Clinical symptoms – Skin findings, nerve tumors, hearing issues.
• Medical imaging – MRI or CT scans to detect tumors.
• Genetic testing – Confirms the presence of NF-related mutations.
• Eye exams – To check for Lisch nodules or optic gliomas.

Treatment and Management

There is no cure for neurofibromatosis, but treatment focuses on managing symptoms and complications.

Surgical and Medical Interventions

• Tumor removal – If tumors cause significant symptoms, surgery may be required.
• Radiation therapy – Used for tumors that cannot be surgically removed.
• Chemotherapy – In cases where tumors become cancerous.
• Hearing aids or cochlear implants – Help manage hearing loss in NF2.

Supportive Care

• Physical therapy – Helps with movement and balance issues.
• Pain management – Medications for schwannomatosis-related chronic pain.
• Educational support – For NF1-related learning disabilities.

Prognosis

The outlook depends on the type:

• NF1 – Generally mild, with a normal life expectancy.
• NF2 – More severe; hearing loss and neurological complications may shorten life expectancy.
• Schwannomatosis – Pain is the main concern, but it does not typically affect lifespan.

Epidemiology

• NF1 affects 1 in 3,000 people.
• NF2 affects 1 in 25,000 people.
• Schwannomatosis affects 1 in 40,000 people.

Males and females are affected equally.

History

• 1st Century – Early descriptions of neurofibromatosis.
• 1882 – Friedrich Daniel von Recklinghausen formally describes NF1.
• 1990s-Present – Advancements in genetic testing and targeted therapies.

Related Conditions

• LEOPARD syndrome
• Legius syndrome
• Proteus syndrome
• Klippel–Trénaunay syndrome

See Also

• Neurofibromatosis type 1
• Neurofibromatosis type 2
• Schwannomatosis
• Genetic disorder

External Links

• National Institute of Neurological Disorders and Stroke – Neurofibromatosis Information
• Neurofibromatosis Network
• Genome.gov – NF Information