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.