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Genetic Proximity of Tuberous Sclerosis Complex 2 and ADPKD

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This is a FLAIR image from an MR

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of the brain in an adolescent

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with tuberous sclerosis complex and seizures.

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We can see multifocal areas of cortical

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dysplasia throughout both

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cerebral hemispheres,

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we can see some of these have

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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

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that mTOR pathway. So,

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if you have an abnormality in

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either tuberin or hamartin,

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that that dimer no longer will suppress the

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mTOR pathway and you will get unregulated

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action of that pathway or incompletely

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regulated action.

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That's one of the reasons why exogenous mTOR

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inhibitors can be used to treat some of the

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findings in tuberous sclerosis complex.

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In particular,

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the subependymal giant cell astrocytoma. Now,

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patients with defects in the TSC2 gene,

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often not always,

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often have more severe brain abnormalities

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and more severe and more difficult

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to control seizures. Now,

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one of the things that is an interesting and

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important association to be aware of even

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though it goes outside the brain is this.

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Now,

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we know that tuberous sclerosis complex is

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associated with cystic renal disease and

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associated with formation of renal angiomyolipoma.

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Those renal angiomyolipomas can hemorrhage when

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they get large. But these cysts here,

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this is more than just cystic renal

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disease of tuberous sclerosis complex.

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This is actually autosomal dominant

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polycystic kidney disease. Well,

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it turns out that the gene for autosomal

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dominant polycystic kidney disease is very

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closely located to the TSC2 gene.

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So this patient actually has dual disease due

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to the genetic proximity of the TSC2

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gene and the autosomal dominant polycystic

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kidney disease gene. So,

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right there from imaging,

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we pretty much can be certain that this

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patient has an abnormality of the TSC2 gene.

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Now,

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that's not something typically that you would

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need a radiologist to be able to make the

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diagnosis. There are genetic tests for that.

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But understanding that relationship and

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understanding that there are different gene

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subtypes of tuberous sclerosis complex and

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potentially different management is something

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that's helpful and important to convey

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to the referring physician,

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whether it be a neuro epilepsy, neurologist,

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whether it be a nephrologist,

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an oncologist that you understand what's going

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on with these patients and with

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this disease process.

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So this patient again has tuberous sclerosis

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complex related to TSC2 gene and also an

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abnormality resulting in autosomal

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dominant polycystic kidney disease.

Report

Description

Faculty

Asim F Choudhri, MD

Chief, Pediatric Neuroradiology

Le Bonheur Children's Hospital

Tags

Syndromes

Pediatrics

Neuroradiology

Neuro

MRI

Brain

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