Tuberous sclerosis

Tuberous sclerosis


On our Youtube channel, you’ll find a limited
selection of pathology and patient videos. With Osmosis Prime, you’ll get access to over
700 videos including complete coverage of pathology and physiology and a growing collection
of pharmacology and clinical reasoning topics. Try it free today. Tuberous sclerosis is a genetic condition
that causes growths to form in various body organs. Most commonly affecting the brain, skin, kidneys,
lungs, and eyes. Normally, there are two genes called TSC1
and TSC2 that help control the growth and division of cells in the body. TSC1 encodes the protein hamartin and TSC2
encodes the protein tuberin . Both of these proteins, are tumor suppressors, meaning they
help slow down cell growth and prevent tumors. They do this by combining to form a hamartin-tuberin
protein complex, which binds to and inhibit another protein called mechanistic target
of rapamycin, or mTOR. mTOR activity speeds up the cell cycle and increases cell proliferation
mainly thanks to its effect on protein synthesis. So when mTOR is switched off by the hamartin-tuberin
protein complex, it slows growth and division of cells throughout the body. Individuals with tuberous sclerosis have a
mutation in either the gene TSC1 or TSC2, and these mutations have an autosomal dominant
inheritance pattern. The mutations lead to an altered hamartin-tuberin
protein complex that’s unable to switch off mTOR. Because of that, benign tumors and growths
called hamartomas form throughout the body. Hamartomas are kind of like tumors, but they’re
made of a variety of cell types from the tissue where they arise, rather than a single cell
type. In fact, if we think of the tissue like a
sheet of fabric, a hamartoma is like a knot in the sheet. Benign tumors and hamartomas can form in any
tissue, but the brain and the skin are usually affected the most, along with the kidneys,
lungs and eyes. On top of that the lifetime risk of cancer
is increased in individuals with tuberous sclerosis. That’s because the rapidly dividing cells
can develop additional mutations that eventually make these growths expand beyond the basement
membrane and invade neighboring tissues. In the brain, the most common growths are
glioneural hamartomas, also known as a cortical tubers. They arise from supportive glial cells as
well as neurons. Next most common are subependymal nodules,
which are hamartomas that form under the ependyma, the thin membrane that lines the ventricles
in the brain. Individuals are also at an increased risk
of developing a subependymal giant cell astrocytoma, or SEGA, which is a type of cancer that can
arise from the subependymal nodules. On the skin, many small growths called angiofibromas
appear on the face. Individuals also have many small bumps called
fibromas under the nails, known as subungual fibromas. Light, flat patches also appear on the trunk
called ash leaf spots and a distinctive dark, raised patch on the forehead is a common feature. Another classical feature is a shagreen patch,
which is a large, elevated, skin colored patch, that often appears on the lower back. Individuals with tuberous sclerosis can develop
renal tumors called angiomyolipomas. Although benign, they can get really big and
put pressure on the kidney. Because the kidney has a lot of blood vessels,
angiomyolipomas do as well, and they can bleed spontaneously. Individuals can also have lymphangioleiomyomatosis
in the lungs, which are cysts where the normal lung tissue is gradually replaced by cysts
lined by endothelial cells, which are the cells that normally line the blood vessels. Finally, in the retina, the light sensing
part of the eye, hamartomas can form. Symptoms of tuberous sclerosis are often related
to the hamartomas in the brain which cause problems like seizures, learning difficulties,
and cognitive deficits. A large angiomyolipoma can cause flank pain,
a lymphangioleiomyomatosis in the lungs, can cause shortness of breath, and a retinal hamartoma
can cause vision changes. Diagnosis is usually made on based on the
skin lesions and can be confirmed with genetic testing to identify a mutation in TSC1 or
TSC2. A head CT or MRI can identify hamartomas and
tumors in the brain, and is usually performed regularly to screen for new lesions. Treatment of tuberous sclerosis is focused
on symptoms. Antiepileptics are used to control seizures. Brain tumors are managed surgically or with
chemotherapy, and behavioral and developmental problems are managed through therapy and psychiatric
medications. All right, as a quick recap… Tuberous sclerosis is a multisystem, autosomal
dominant genetic condition caused by mutations in genes TSC1 or TSC2. The mutations lead to an altered hamartin-tuberin
protein complex that’s unable to switch off mTOR. It causes benign tumors and hamartomas to
grow in the brain, the skin, the kidneys, the lungs, and the eyes.

23 Comments

  • Jp. Blooten says:

    <3 Very Helpful We Love You !

  • Myestro 86 says:

    Very helpful thank you .. but if you can add some menomenic ๐Ÿค—

  • Adriana Rarumi says:

    I am currently on vacation but I can't resist a Osmose video <3

  • chareese angela abat says:

    Please make a video of TUBERCULOSIS OF THE SPINE PLEASE THANKS

  • said hegazy says:

    Very simple very helpful thanks a lot love u much

  • Nixon Lee says:

    Great! Knowledge is power!

  • Penta Comstat says:

    One of the pleasures I enjoy when consuming Osmosis videos is the V O I C E. But this time there is a different voice. I apologise to the person speaking this video but I prefer the previous voice. When you have the perfect recipe… WHY CHANGE IT? Typical humans, always meddling until it is destroyed. I've had a wonderful time with Osmosis, perhaps it's time to move on. ALL THINGS PASS. 17JUL2018 P.S. The content herein is excellent as usual.

  • zoetrope says:

    Excellent education

  • Winston Dollete says:

    Hello Osmosis! Your videos helped me alot. Could you also make videos about the normal physiology of certain systems in the body? Just for a good review about the subject matter. Thank you!!!

  • Fatih Seker says:

    Thank you nice video.Can you make infantile spasm and lennox-gasteut type epilepsy videos.

  • brownandproud Hernandez says:

    Good job on teaching us some diseases..๐Ÿค—๐Ÿค— always good to know

  • AGSC says:

    Just for completeness: The genes involved in TS are on –> Ch.9 = TSC1(hamartin) & Ch.16 = TSC2(tuberin). It's easy to assume they're located in the same Chromosome !

  • MySoulzASong says:

    I just found out today that my 2 year old daughter may have tuberous sclerosis. We went in for an autism screening thinking that would be the diagnosis…not another symptom. I don't think this video should have been my first information source on TSC, not because it wasn't informative, but because this is my baby girl and I can't imagine her having to go through any of that.

  • Ice Man says:

    Shit, that was awesome

  • C Blossom says:

    My son was born with bi lateral hydronephrosis. He didn't need any interventions growing up. Just went though a lot of screening and diagnostics. He's goes in regularly for Ultra Sounds. These became infrequent because his functions and growth became more normal. Except for the right side was a little more impaired. He's going to be 17 yrs old soon. He went in for his follow up Ultra Sound recently. They found angiomyolyphomas a lot on both kidneys… The MRI to the abdominal confirmed it. He just did a brain MRI and it showed tiny frontal lesions… I never heard of TSC before nor did I ever think this could happened to my kid. He's grown up very well, no problems. Just bad acne. He started off being small but just before High School he grew 5 inches and is now standing 5' 9". Slender built, big smile, big heart and very considerate to others. He done well in school all his life a bit of an over achiever… but it's not bad. He's an Eagle Scout, National Honors student and will be graduating High School in May 2019 and hoping to get into a pre med program in college. This has been very hard for me to swallow… TSC has not been confirmed yet because we need to see the Geneticist to test for the mutation. I'm just feeling so overwhelmed that my beautiful smart kind heart son is going to deal with this. This all took us by surprise. He shows no signs nor symptoms except for the acne and angimyolyphomas in the kidneys. My heart hurts and I've been trying to keep a brave face as we are waiting for his Dr. to explain this to him, which is coming up October 20th. I think he knows something is going on as he's been very depressed and withdrawn. He's not a dummy and knows we are not saying anything until it's been confirmed. I just don't know what to tell him and I don't know if his whole life's dream will be altered because of this. He wants to be a Doctor and have a family in the future. I know this might change… I've always taught my kids that what happens today does not define who you will be tomorrow. I'm just not sure now about tomorrow…

  • Miguel Ortega Ledesma says:

    not very help but thanks

  • Varun Sharma says:

    isn't rhabdomyoma associated with tuberous sclerosis?

  • Sudipan Roy says:

    Nice video. But I think you should need to talk about Rhabdomyoma also.

  • Sandy Martynov says:

    10-15% of people with tsc actually donโ€™t have mutations in tsc1 or tsc2. I did the genetic testing since I have tsc and they did not find any mutations in those genes. Hopefully a third gene mutation that cause tsc might be found in the future so we can learn even more ๐Ÿ™‚

  • amira asaad says:

    there is no mention of cardiac Rhabdomyoma

  • amira asaad says:

    i love osmosis

  • fatima ttr says:

    My brother has this disease how can I help him in home?

  • Parinitha Maben says:

    Awesome! ๐Ÿ™‚

Leave a Reply

Your email address will not be published. Required fields are marked *