00:01
So what is tuberous sclerosis?
And what are we going to learn about
when we think of this condition?
Well, we're going to talk about
this lesion, this skin finding
an ash-leaf macules that we've
mentioned a couple of times.
00:12
We'll talk about tumors
or hamartomas gross
that can occur
anywhere in the body,
particularly the malar regions
of the face.
00:19
And we'll learn about angiofibromas,
or facial angiofibromas.
00:23
Will look at the skin,
will look at the nails
all the way out
to the surface of the patient.
00:27
And we'll think about findings
that could occur in those areas.
00:29
And you can see these
small gross on the nail bed
or periungual fibromas,
or gross around the nail bed.
00:36
And we'll remember
to look at the entire skin
and do a full skin exam,
for these patients
and look for a shagreen patch,
or another characteristic
clinical finding in these patients.
00:47
We'll also know to do imaging.
00:49
And by the end of learning about TS
we'll know to look at
the kidneys and the brain
for characteristic findings
that we could see
in each of those locations.
00:59
So what is TS?
What is tuberous sclerosis?
Well, this is another autosomal
dominant inherited condition
that results from a mutation
in one of two genes,
the TSC1 gene,
or the TSC2 gene.
01:13
TSC1 encodes a protein hamartin,
and TSC2 a protein tuberin.
01:19
Both are tumor suppressor genes,
and this is another one
of our prototypical
tumor suppressor syndromes.
01:26
Loss of one gene
is insufficient to result
in full clinical manifestations
of the disease.
01:32
Tumors developed from
loss of heterozygosity,
loss of that second
tumor suppressor.
01:38
This condition therefore fulfills
the two-hit hypothesis
and explains why there is a range
of symptoms and a range of findings,
there is again complete penetrance
every TS patient
will have some manifestation,
but variable expressivity.
01:51
A mom and a child,
a brother and a sister
may have very different
manifestations of this condition.
01:59
Tuberin and hamartin
are proteins that normally act
to stop the cell cycle,
stop cell growth
and involve a protein called mTOR.
02:07
Loss of these proteins
results in dysregulated growth
or increase in cellular mTOR,
and tumors are allowed to grow.
02:16
Some of the findings
that we see here ash-leaf macules,
these are hypopigmented lesions,
often with a straight line
on one side
and a tapered line on the other
giving in this characteristic
leaf appearance.
02:28
And are can pre present it
anywhere on the body,
the torso, and the extremities.
02:33
Angiofibromas are benign tumors,
they're hamartomas
its excess growth
from unregulated mTOR
loss of tuberin and hamartin
within those cells, in the skin,
the malar area of the face,
and we see facial angiofibromas
primarily in the cheeks,
and the forehead.
02:49
The periungual fibromas I mentioned,
which are lesions that occur
around the skin and nail bed
and a shagreen patch
is a connective tissue lesion
that typically forms
on the lower part of the back.
03:00
and this image is the lower part
of the back, the back area.