Neurofibromatosis Type 2: Introduction

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.