Tuberous Sclerosis: Introduction

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.