Neurofibromatosis

Definitions & Key takeaways

Neurofibromatosis is a genetic disorder characterized by fibrous tumors that affect the development and function of the nervous system. There are three known types of neurofibromatosis: neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis.

NF1 is due to a mutation in the NF1 gene on chromosome 17, and generally affects the skin and extremities. NF1 causes cutaneous neurofibromas (benign tumors that grow from the nerve sheath), caf-au-lait spots (flat patches with milky-coffee color), and Lisch nodules (small tan colored bumps). NF2 is caused by a mutation in the NF2 gene on chromosome 22, and is associated with bilateral acoustic neuromas that can cause tinnitus, and bilateral gradual loss of hearing. NF2 is also associated with multiple meningiomas in the brain and spinal cord.

Schwannomatosis is a rare form of neurofibromatosis, characterized by multiple schwannomas, pain, and numbness in the affected areas. Unlike NF2, schwannomatosis spare the vestibular nerve.

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Introduction0:00–0:18

With neurofibromatoses, neuro refers to the nerves, fibro- refers to fibrous tissue, and -oma means growth, or tumor. So neurofibromatosis refers to fibrous tumors originating from the nervous system.

Physiology0:18–1:11

The body’s central nervous system is made up of the brain and the spinal cord, which are surrounded by three protective layers called the meninges.
Part of the central nervous system are the cranial nerves, which originate in the brainstem and innervate the head and neck, and the spinal nerves, which originate in the spinal cord, and supply the rest of the body.
Each nerve is surrounded by a nerve sheath, which is produced by cells called fibroblasts. Inside, each nerve there are several fascicles, and each fascicle, in turn, is made up of several axons.
The axons are the long projections of neurons, that carry the information as electrical signals running up and down their length.
Along the axon there are cells called Schwann cells, which produce a myelin cover for the axon. The myelin helps electrical signals travel along the axon faster.

Causes1:11–2:06

Now, neurofibromatoses are genetic diseases which cause non-cancerous growths to form in the body’s nerve tissue, and there are two types - type I and type II.
They’re caused by inheriting faulty copies of either the NF1 or NF2 gene, which are found on chromosomes 17 and 22, respectively.
Just remember, NF1 goes with chromosome 17 and NF2 goes with chromosome 22. Both of these have an autosomal dominant inheritance pattern, so a child only needs one faulty copy from either parent to get the disease.
Normally, these are tumor suppressor genes, which means they stop cells from dividing uncontrollably. So when there’s a mutation in the gene, it leads to uncontrolled growth of fibromas which are growths that have multiple cell types including neurons, Schwann cells, and other supporting connective tissue.

Neurofibromatosis type I2:06–3:37

Neurofibromatosis type I, is also called von Recklinghausen’s syndrome typically affects the nerves in the extremities and the skin.
It causes lots of neurofibromas, which are benign tumors that grow from the nerve sheath and are made of a mixture of Schwann cells, fibroblasts, and immune cells.
Usually, they grow just beneath the skin surface, but they can also grow along peripheral and spinal nerves. Cutaneous neurofibromas typically start forming in childhood and increase in number over time.
They appear as a painless, mobile lumps under the skin. On top of that, people with type I neurofibromatosis often have skin markings called café-au-lait spots, which are flat patches that are the color of milky coffee.
These spots typically appear on the back, the buttocks, and the thighs in the first year of life, and increase in number over time.
Also, on an eye exam, there are small tan colored bumps called Lisch nodules can be seen on the iris. These nodules almost always appear by the age of 6, but don’t usually cause any sight problems.
However, with neurofibromatosis 1 there’s an increased risk of other problems in the nervous system like seizures, learning difficulties, and malignant peripheral nerve sheath tumors.
Occasionally, large neurofibromas can develop in the abdominal cavity, and they can press against nearby organs, like the kidneys, and impair their function.

Neurofibromatosis type II3:37–5:02

Neurofibromatosis type II, on the other hand, typically affects the brain, spinal cord, and cranial nerves. In neurofibromatosis type II, skin neurofibromas and café-au-lait spots are less common.
However, people with neurofibromatosis type II typically develop schwannomas - which are tumors comprising only of Schwann cells.
These tumors can develop in the spine or along the cranial nerves. Most commonly, these tumors which are also called acoustic neuromas, develop along the eighth cranial nerve.
Acoustic neuromas can occur in individuals that don’t have neurofibromatosis, but in neurofibromatosis type II they tend to occur bilaterally.
Acoustic neuromas can cause tinnitus, or a ringing sound in the ears, and gradual loss of hearing on both sides. Individuals may also develop tumors called meningiomas, which are benign tumors originating in the meninges.
If they develop in the spinal meninges, the meningiomas can compress the spinal cord, leading to pain, numbness, and weakness in the extremities.
If they develop in the cerebral meninges, they can cause seizures or visual changes, and muscle weakness. People with neurofibromatosis type II can also develop eye problems, like cataracts, or small defects called hamartomas in the retina.

Diagnosis5:02–5:23

Diagnosing neurofibromatosis is based on a physical exam focused on the skin, the eyes, and the ears. Tumors in the brain, cranial nerves, and spinal cord can be diagnosed using CT or MRI.
And genetic testing can be used to confirm the NF1 or NF2 mutation. There’s no specific treatment or cure for neurofibromatosis but surgery can be used to remove tumors that are compressing nearby organs.

Treatment5:23–5:32

All right, as a quick recap… There are two kinds of neurofibromatosis. Type I is caused by a mutation in the NF1 gene and causes cutaneous neurofibromas, café-au-lait spots, and Lisch nodules.

Review5:32–6:11

Type II is caused by a mutation in the NF2 gene which causes bilateral acoustic neuromas and multiple meningiomas in the brain and spinal cord.
NF1 goes with chromosome 17, and NF2 goes with chromosome 22. Diagnosis can be confirmed with genetic testing to confirm the NF1 or NF2 mutation, and surgery can be done to remove some tumors.