What are the other Names for this Condition? (Also known as/Synonyms)

• Acoustic Neurofibromatosis (due to Neurofibromatosis Type 1)
• Type IV Neurofibromatosis of Riccardi
• Von Recklinghausen Disease

What is Neurofibromatosis Type 1? (Definition/Background Information)

• Neurofibromatosis is a multisystem genetic disorder affecting the nervous system, skin, and skeletal muscles
• Neurofibromatosis Type 1 (NF1) manifests as benign tumors developing from the layer covering the cutaneous (skin) and optic (eye) nerves .This results in disfiguring outgrowths from the skin. When these lesions become multiple and locally-invasive, it is called plexiform neurofibromatosis
• Neurofibromatosis Type 1 is caused by mutation in the neurofibromin (NF) gene resulting in the decreased production of a protein called neurofibromin, which acts as a tumor suppressor protein. Though mutations in NF-gene occur during birth, the clinical manifestations take some years to develop
• The diagnosis of Neurofibromatosis Type 1 is made by a genetic test. In this test, in 95% of the cases, molecular sequencing of NF1 gene is positive
• Malignant transformation of the neurofibromas (skin outgrowths), spinal cord and brain tumors, and proliferation of the tumor during pregnancy and puberty are some of the complications associated with Neurofibromatosis Type 1
• The treatment is mainly focused on the early detection of complications and treating them. Presently, there are no effective ways to prevent Neurofibromatosis Type 1

Who gets Neurofibromatosis Type 1? (Age and Sex Distribution)

• Neurofibromatosis Type 1 is a congenital condition that is present at birth. However, the signs and symptoms may take some time (years) to develop
• Both men and women are affected by this condition
• African-Americans are at lower risk of developing optic (eye) nerve lesions than Caucasians and Hispanics

What are the Risk Factors for Neurofibromatosis Type 1? (Predisposing Factors)

• A family history of neurofibromatosis is the main risk factor associated with Neurofibromatosis Type 1

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Neurofibromatosis Type 1? (Etiology)

• Neurofibromatosis Type 1 is caused by autosomal dominant transmission of NF 1 gene mutation on chromosome 17
• Even though most of the affected individuals have NF-1 gene mutation, in many, spontaneous mutations are seen to occur. There is no presence of any family history of the condition in such individuals
• If an individual who is at risk is not showing clinical manifestations for up to 10 years of age, there is a chance that he/she is less likely to be affected

What are the Signs and Symptoms of Neurofibromatosis Type 1?

Following are the signs and symptoms of Neurofibromatosis Type 1. These are also the clinical criteria for diagnosing NF 1. Any 2 of the 7 criteria (below) should be present to diagnose NF 1.

• Six or more café-au-lait spots: These are hyperpigmented macules on the skin, greater than or equal to 5 mm in diameter in children (younger than 10 years)  and up to 15 mm in adults
• Axillary or inguinal freckles
• Two or more typical neurofibromas (skin outgrowths) or one plexiform neurofibroma
• Optic nerve glioma (proliferation in the nerve sheath surrounding the optic nerve)
• Two or more nodules in the iris (muscle around the pupil of the eyes) called Lisch nodules, often identified only through slit-lamp examination by an ophthalmologist
• Typical long-bone abnormalities such as pseudarthrosis. It is the bowing of the long bones such as tibia (one of the leg bones)
• First-degree relative with NF1 (such as mother, father, sister, or brother)

How is Neurofibromatosis Type 1 Diagnosed?

The diagnosis of Neurofibromatosis Type 1 may involve:

• Complete evaluation of medical history and a thorough physical exam
• Sequencing of the NF 1 gene detects 95% of the cases. It can be helpful in detecting patients with single clinical manifestation and absent family history
• MRI scan of brain is used to detect optic nerve tumors
• Plain x-ray of the spine and long bones can help rule out scoliosis and bowing respectively

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Neurofibromatosis Type 1?

Complications associated with Neurofibromatosis Type 1 include:

• Malignant transformation of the neurofibromas (skin outgrowths)
• Spinal cord and brain tumors
• Proliferation of the tumor during pregnancy and puberty
• Gastrointestinal (GI) stromal tumors causing GI bleeding and intestinal obstruction
• Learning disabilities
• Bone disorders, which include scoliosis and bowing of long bones. The severity of scoliosis is greater in females than males
• Hypertension
• Osteoporosis associated with vitamin D deficiency
• Short stature

How is Neurofibromatosis Type 1 Treated?

The treatment of Neurofibromatosis Type 1 is mainly focused on early detection of complications and treating them.

• During every visit , the physician may look for the development of new lesions
  • Annual ophthalmic exam is required to detect iris nodules
  • Skeletal examination to look for scoliosis, manifestations of spinal tumors, bowing of long bones    Blood pressure should be checked periodically
• Cosmetically disfiguring lesions can be surgically removed
• Plexiform lesions should be removed carefully as it may result in excessive bleeding and nerve injuries after removal
• Malignant growths should be treated appropriately

How can Neurofibromatosis Type 1 be Prevented?

• Currently, there are no specific methods or guidelines to prevent Neurofibromatosis Type 1, since it is a genetic condition
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

What is the Prognosis of Neurofibromatosis Type 1? (Outcomes/Resolutions)

• Most Neurofibromatosis Type 1 lesions are benign. They may pose cosmetic issues, but malignant transformation of the tumors are very rare
• The prognosis is good if periodic health checkups and assessments are undertaken for expected complications

Additional and Relevant Useful Information for Neurofibromatosis Type 1:

Neurofibromatosis type 2 (NF2) is a genetic disorder characterized by bilateral non-cancerous tumors in the vestibular nerve. The vestibular nerve is responsible for hearing.