00:01
These are all
genetic conditions
and we're going to learn
about the genetics of NF1 and NF2.
00:06
First, we'll focus on NF1.
00:08
NF1 results from a mutation
in the NF1 gene.
00:12
The NF1 gene encodes a protein
called neurofibromin,
which you see here.
00:16
And neurofibromin
is a break.
00:18
It is a tumor suppressor,
it slows down growth.
00:21
And when it's normally
functioning in the cell,
the RAS pathway, which is the most
common cell proliferation pathway
is slowed down.
00:29
RAS cannot cause the cells to grow.
00:32
When you lose neurofibromin,
cell growth is uninhibited
and cells are able to grow.
00:38
And one of those
cell growth signals is MEK.
00:40
And we're going to come back to this
at the end of the lecture
when we talk about treatment.
00:44
But that's an important
downstream protein
that causes cells to grow
and proliferate
and contributes
to tumor formation
in neurofibromatosis type 1.
00:55
So how do we
diagnose patients within NF1?
Well, it's a genetic condition,
but we actually often
don't test the genes.
01:02
We can...
01:03
we can look for that
specific mutation in the NF1 gene
that's causing this condition.
01:07
But as I said,
it's one of the most,
it's one of the biggest
genes in the human body.
01:12
And it's very difficult to test all
of the mutations that may occur.
01:16
So primarily, we rely
on a clinical diagnosis.
01:19
And there are seven features
that I want you to think about
when making
a clinical diagnosis of NF1.
01:25
The first are
Cafe-au-lait macules.
01:27
And we saw those in an image
and we'll look at a few more.
01:30
And six or more cafe-au-lait macules
is sufficient to make a diagnosis
or part of a diagnosis of NF1.
01:36
In prepubertal individuals,
those must be greater
than five millimeters
and postpubertal individuals
greater than 15 millimeters.
01:44
The second criterion
are neurofibromas.
01:47
And we also looked at those
for our patient.
01:49
Those are the lesions that we see
out on the skin, the bumps.
01:52
And two or more
dermal neurofibromas
or one plexiform neurofibroma
is sufficient for a major criteria
for diagnosing neurofibromatosis.
02:01
We'll look at axillary and inguinal
freckling or skinfold freckling,
which is also
one of the seven criteria.
02:07
Optic pathway gliomas.
02:09
Lisch nodules, which was present
in our patient in case.
02:12
Osseous abnormalities.
02:14
We'll talk about
sphenoid winged dysplasia,
and pseudarthrosis.
02:18
And a family history.
02:20
Patients must have
two of these seven criteria
to be clinically diagnosed
with NF1.
02:27
There are also additional
symptoms and signs
that we can see
in these patients.
02:30
That aren't sufficient
to establish a diagnosis,
but can be highly contributing
to the evaluation and management
of these patients.
02:39
Cardiovascular malformations
can occur.
02:40
We think of coarctation of the aorta
or renal artery stenosis,
which can occur later in life
or in adolescent individuals.
02:47
Learning disabilities are
extremely common in these patients
and occur in up to 75%
of this group of patients.
02:54
ADHD,
Attention Deficit Disorder,
as well as
Hyperactivity Activity Disorder
is also common.
03:00
Osteoporosis in Peenya,
thinning of the bones,
pectus excavatum, which is
invagination of the sternum.
03:07
Bony abnormality that can occur.
03:09
Pheochromocytoma is another tumor
that occurs on the adrenal glands
and can cause
elevated high blood pressure
in these patients.
03:16
Glomus tumors on the skin
or under the nails.
03:19
Gastrointestinal stromal tumors
those are called GIST tumors,
neat tumors that occur
in the GI tract and are uncommon
but can be seen in NF1.
03:28
Juvenile myelomonocytic
leukemia,
which is a very difficult to
complication of this condition.
03:33
It's rare, but can occur
in young adolescents.
03:36
Dural ectasia, scoliosis,
and early onset breast cancer.
03:40
So almost all organ system
can be involved in NF1.
03:44
And we're going to focus on those
that establish the diagnosis
and other principal organs
to be affected.