0:01

This is a FLAIR image from an MR

0:02

of the brain in an adolescent

0:04

with tuberous sclerosis complex and seizures.

0:07

We can see multifocal areas of cortical

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dysplasia throughout both

0:12

cerebral hemispheres,

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we can see some of these have

0:15

a cystic component.

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So these are classic findings of

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tuberous sclerosis complex. Now,

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it's important to note there are two different

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genes involved in the tuberous sclerosis complex.

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There's the TSC1 gene and the TSC2 gene,

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the TSC1 and TSC2 genes produce

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the proteins tuberin and,

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and hamartin which come

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together and together,

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they are a regulatory protein

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in the mTOR pathway.

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They suppress that pathway

0:48

that mTOR pathway. So,

0:51

if you have an abnormality in

0:53

either tuberin or hamartin,

0:55

that that dimer no longer will suppress the

0:59

mTOR pathway and you will get unregulated

1:04

action of that pathway or incompletely

1:06

regulated action.

1:07

That's one of the reasons why exogenous mTOR

1:10

inhibitors can be used to treat some of the

1:13

findings in tuberous sclerosis complex.

1:15

In particular,

1:16

the subependymal giant cell astrocytoma. Now,

1:20

patients with defects in the TSC2 gene,

1:24

often not always,

1:26

often have more severe brain abnormalities

1:30

and more severe and more difficult

1:32

to control seizures. Now,

1:35

one of the things that is an interesting and

1:40

important association to be aware of even

1:42

though it goes outside the brain is this.

1:46

Now,

1:47

we know that tuberous sclerosis complex is

1:52

associated with cystic renal disease and

1:54

associated with formation of renal angiomyolipoma.

1:57

Those renal angiomyolipomas can hemorrhage when

2:00

they get large. But these cysts here,

2:04

this is more than just cystic renal

2:06

disease of tuberous sclerosis complex.

2:08

This is actually autosomal dominant

2:10

polycystic kidney disease. Well,

2:12

it turns out that the gene for autosomal

2:16

dominant polycystic kidney disease is very

2:18

closely located to the TSC2 gene.

2:21

So this patient actually has dual disease due

2:26

to the genetic proximity of the TSC2

2:29

gene and the autosomal dominant polycystic

2:32

kidney disease gene. So,

2:34

right there from imaging,

2:37

we pretty much can be certain that this

2:40

patient has an abnormality of the TSC2 gene.

2:44

Now,

2:45

that's not something typically that you would

2:47

need a radiologist to be able to make the

2:49

diagnosis. There are genetic tests for that.

2:52

But understanding that relationship and

2:55

understanding that there are different gene

2:58

subtypes of tuberous sclerosis complex and

3:03

potentially different management is something

3:05

that's helpful and important to convey

3:08

to the referring physician,

3:11

whether it be a neuro epilepsy, neurologist,

3:14

whether it be a nephrologist,

3:17

an oncologist that you understand what's going

3:20

on with these patients and with

3:22

this disease process.

3:23

So this patient again has tuberous sclerosis

3:26

complex related to TSC2 gene and also an

3:30

abnormality resulting in autosomal

3:32

dominant polycystic kidney disease.