‌

Neurofibromatosis

‌‌

21,248views

00:00 / 00:00

‌‌
‌
‌
‌‌‌‌‌‌‌‌‌‌
‌
‌‌‌

High Yield Notes

13 pages

Flashcards

Neurofibromatosis

of complete

Questions

USMLE® Step 1 style questions USMLE

of complete

A 19-year-old man comes to the clinic due to a feeling of unsteadiness over the past few months. At first, the patient felt more clumsy and often bumped into furniture around the house. More recently, he has been feeling wobbly and often loses his balance. Additionally, the patient states that over this same time period, he needs to raise the volume on the television in order to hear it better. He denies any trauma and does not use tobacco, alcohol, or illicit drugs. Family history is unremarkable. Vitals are within normal limits. On physical examination, the patient has difficulty standing with the feet together and almost falls. He is unable to hear whispering voices bilaterally. An MRI is obtained and shows a 2 cm lesion at the right cerebellopontine angle and a 3.5 cm lesion at the left cerebellopontine angle. This patient is at risk for developing which of the following?  

Memory Anchors and Partner Content

External Links

Transcript

Watch video only

Content Reviewers

Rishi Desai, MD, MPH,Yifan Xiao, MD,Viviana Popa, MD

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.

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.

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.

Summary

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.

Sources

  1. "Robbins Basic Pathology" Elsevier (2017)
  2. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  3. "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
  4. "CURRENT Medical Diagnosis and Treatment 2020" McGraw-Hill Education / Medical (2019)
  5. "Neurofibromatosis" Orthopaedics and Trauma (2015)
  6. "Review Article : Molecular and Cellular Mechanisms Underlying the Cognitive Deficits Associated With Neurofibromatosis 1" Journal of Child Neurology (2002)
  7. "The Neurofibromatosis 2 Tumor Suppressor Gene Product, Merlin, Regulates Human Meningioma Cell Growth by Signaling through YAP" Neoplasia (2008)