Neurofibromatosis Type 2: Introduction

by Roy Strowd, MD

My Notes
  • Required.
Save Cancel
    Learning Material 2
    • PDF
      Strowd CNS Tumors Inherited Tumor Syndromes.pdf
    • PDF
      Download Lecture Overview
    Report mistake

    00:00 So what is NF2? What used to be called central neurofibromatosis.

    00:06 NF1 was peripheral neurofibromatosis, NF2 was central neurofibromatosis, because a lot of the manifestations are central.

    00:15 Patients can have peripheral nervous system findings, and we'll talk about those.

    00:19 So this is an old adage, but I think it's a helpful reminder of where we need to focus.

    00:23 We'll need to do neuroimaging of the brain, and brainstem, and spinal cord, and we'll need to look for those central manifestations.

    00:30 NF2 is not as common as NF1, but it can be more severe.

    00:34 And so it's very important to have on a clinicians radar.

    00:38 In contrast to NF1, which affects about one in 3000 individuals NF2 affects one in 50,000.

    00:44 So you can see the degree of commonality and prevalence of this condition in comparison to NF1.

    00:52 And it's characterized by schwannomas.

    00:54 With NF1, the tumors we see are neurofibromas.

    00:57 And with NF2, the tumors we see are schwannomas.

    01:00 Different types of peripheral nerve sheath tumors.

    01:04 And we can look at that histologically and see that schwannomas have these characteristic two regions, Antoni A and Antoni B regions, which we don't see in neurofibromas.

    01:14 Not things I need you to note how to look at, but buzzwords that would be important on a test question or clinical vignette.

    01:21 And here you can see in this patient a good example on this coronal T1 postcontrast image of a vestibular schwannoma.

    01:27 Starting in the internal auditory canal, that canal that extends out into the ear and ear canal region, and then is bobbing into and compressing the brainstem.

    01:40 NF2 results from a mutation in the NF2 gene, which is located on chromosome 22, which you can see depicted here.

    01:48 NF2 results from a mutation in the NF2 gene.

    01:51 And that gene encodes a protein, Merlin, or schwannomin.

    01:55 And again, that's a tumor suppressor protein.

    01:58 It puts two breaks or you need two breaks on tumor cell growth.

    02:03 This is an autosomal dominant condition, but there can be mosaicism.

    02:08 The vast majority of patients will acquire mutation in the NF2 gene, that is germline.

    02:13 All cells in the body contain the NF2 mutation.

    02:16 But sometimes the acquired mutation in the NF2 gene occurs after conception.

    02:22 Downstream of the initial embryogenesis.

    02:26 And this results in one part of the body or one location, that suffers from NF2 abnormality or an NF2 mutation, and that's called mosaicism.

    02:35 Chromosome 22 is a neat chromosome.

    02:37 There's a bunch of genes on that chromosome.

    02:40 And I'd like for you to think of three of those genes, the LZTR1 gene, the SMARCB1 gene, and the NF2 gene.

    02:49 Patients who have mutation in the NF2 gene will suffer from neurofibromatosis type2.

    02:55 Additional mutation of SMARCB1 and LZTR1, it results in the development of schwannomatosis, which is similar and related but different from NF2.

    03:06 So let's go back to that initial genetic slide and understand how Merlin and neurofibromin are related? Again, NF2 is a genetic condition.

    03:16 It results from an abnormality in the NF2 gene, in the Merlin or schwannomin protein.

    03:22 Loss of the NF2 gene results in loss of function of that Merlin protein.

    03:27 Merlin is involved in a number of different things.

    03:30 And while it's very clear what neurofibromin does in NF1 it's less clear how Merlin contributes to tumor cell growth.

    03:37 But loss of Merlin is sufficient to drive tumor cell growth in characteristic areas of the nervous system.

    About the Lecture

    The lecture Neurofibromatosis Type 2: Introduction by Roy Strowd, MD is from the course CNS Tumors.

    Included Quiz Questions

    1. Antoni A and B regions
    2. Pseudopalisading pleomorphic cells
    3. Spindle cells arranged in a whorled pattern
    4. Chicken-wire capillary pattern
    5. Rosettes with small blue cells
    1. Merlin
    2. GNAS1
    3. Menin
    4. Hamartin
    5. MEC

    Author of lecture Neurofibromatosis Type 2: Introduction

     Roy Strowd, MD

    Roy Strowd, MD

    Customer reviews

    5,0 of 5 stars
    5 Stars
    4 Stars
    3 Stars
    2 Stars
    1  Star