DIP Episode 662 - The Genetics Sprint (for Step 2 and 3) Part 2

All right, welcome. My name is divine. This is a piece of 662 of the divine intervention podcasts. And into this podcast will be continuing the genetic sprint. If you missed 661, that's part one of the series. I'll strongly encourage you to go back and listen to it. Let's begin. So what if they give you a question about a 19-year-old? And you're told that this 19-year-old male comes to the emergency room because he has a very severe headaches. You're told that he's had many episodes like this over the last six months. Has very severe headaches, has like blurry vision. And you're told that he's actually being evaluated right now by an ophthalmologist for a lesion that was found on a fondoscopic exam. And you're told that all that his blood pressure is on presentation is a 190 over 110. So, Cestolic 190, Bastolic 110. If you see something like this, what should you be thinking about? Well, I really hope that you're thinking that this person probably has a feel. And this person probably has like some kind of optic nerve tumor. If you put these two things together, you should make you think of what? I hope you're saying divine, NF1. Your fibromatosis type 1. Right? So again, what are the key things to know here as we walk through this sprint? Well, remember, NF1 is an Orozomodominant disorder. Right? So, Orozomodominant disorder. Right? You certainly want to make sure you know that, right? So, Orozomodominant disorder. And the mutation is in the mutation is in neurofibromine.

Right? Eurifibromine is a it's a it's pretty much like a thing that suppresses rust signaling. You know, I think some of you may not realize this, but the USMEL is these days. They like to put answer choices that are a little bit removed from what you know. It's just kind of like a nice protection against people that don't understand pathophysiology or don't, you know, just blindly memorize stuff. So, just remember that it's basically a mutation in the tumor suppressor gene. Right? Something that normally suppresses rust signaling. But so, RAS. But if you have this mutation, then you won't be able to suppress rust signaling. And you're going to have a lot of tumors forming. Right? You're going to have a lot of tumors forming. That's the job of neurofibromine. So, again, NF1 is a problem with chromosome 17 with a neurofibromine gene. Right? Now, what are the classic findings in this disease? Well, you're going to see things like coffee or leaf spots. Remember, those tend to be hyperpigmented. And then they're going to have these neurofibromas. That's why it's called neurofibromatosis. They're going to have some eye problems. They're going to have like lesionogils of the iris. Those are iris, are hematomas. They can have optic nerve gliomas. They can have optic nerve gliomas. So, that can cause an afferent, popularity effect on your ex-apps. Remember, they can have like axillary and ingrownal freckling. So, the crevices of their bodies, they can have freckles. Right?

And, again, remember, chromosome 17. That's the key thing to remember with the chromosome where it inherited from. Now, one thing I'm just going to say is, why was the person's blood pressure high? Well, it was high because they had a feel. Right? Remember, for purposes of the USMEL exams, they really do want you to know the disorders that have an association with fereochromocytomas. Right? Now, what are those disorders? Don't forget that any in two, the immune to have an asiomod of fereochromocytoma. NF1 has an asiomod of fereochromocytoma. And VHL, from people in doubt, you may notice that all these things are a lot more dominant disorders. They all have associations with fereochromocytomas. So, I'll certainly know that for exams if I were you. Now, one of the things I just want to kind of throw out here is, people that have NF1, is there a particular screening guideline you think makes sense for these people? Well, I hope you're seeing that we've defined these will probably be getting an un-o-i exams, which makes sense. Why? Because again, these people, they have a lot of eye problems. Right? They have a lot of eye problems. So, you make sense that it should be getting a lot of eye exams. Right? Now, you want to be able to compare contrast NF1 with NF2. Right? So, remember, NF2 is a chromosome 22 defect on like NF1, that's a chromosome 17 defect. Right? Now, the thing you need to know about NF2 is that the mutation is in a gene known as Merlin. Right?

It's a Merlin gene mutation. It's also a zone of dominance. Right? And again, the mutation is in a tumor suppressor gene. It's in a tumor suppressor gene. Right? So, the thing is, NF2, it encodes us something called a Merlin. Right? Sometimes on exams, you may see them refer to it as Shuanoming, SCHWA, WNOMN, O-M-I-N, Shuanoming. Right? It's a tumor suppressor gene, you know, from almost like from a cytoskelo-skelo-perspective. Right? From a cytoskelo-skelo-perspective. But I think the big thing to just know here is many times these people on the exams, they'll have these bilateral vestibular Shuanomas. They can say that, ooh, you see bilateral masses at the cerebellum pontine angle. So, the junction of like the cerebellum on the pond, that's a very common location of vestibular Shuanomas. Sometimes they call those acoustic neuromers. Right? They can talk about the person having like progressive bilateral hearing loss, tinnitus and things like that. Right? Or you may see them having tumors that are in the cerebroconvexidies, right? So, like, meningiomers, or you may see them having hydrosephalus, right? Or increased IC Ps, and then they show you a brain image that shows a fourth ventricular mass. That's an appendiumoma. Right? Remember, these people tend to have Shuanomas, meningiomers, and a appendiumomas. In fact, some people call this mesmy in the land of radiology, MSME. Right? Mesmy. Right? So, the MS stands for multiple Shuanomas. The M stands for meningiomers.

And then the E stands for appendiumomas. Right? So, they have multiple Shuanomas, meningiomers, and a appendiumomas. Right? So, again, make sure you differentiate this from NF1. Right? But, again, remember, please, guys, the USML is the love sort these days. They can literally give you these disorders. And the right answer will be tumor suppressor gene mutation. Or, like, for example, NF1, we talked about how it's, they can tell you something about extensive russ signal, you know, whatever. So, you're just going to keep that at the back of your mind as you prep for your exams. Right? And then what if they give you a question about a child? And they tell you that this child, you know, is brought to the physician for an eye exam. Right? And that mass, you know, a mass is found in the right eye. Right? And then they give you some labs. And you notice that the child has a very high hematocrate. Right? Has a high hematocrate. And then they tell you that, you know, brain imaging shows a mass, you know, not just in the eye. So the try to follow characterize the mass, define the mass, not just in the eye, but also find the mass in the posterior forcer of the head. If you see something like that, what should you be thinking about? But I hope you're thinking that with this person probably has like VHL. Right? This person has VHL. Von Hippolindau. Right? Von Hippolindau disease is very, very high you to know for your exams. It is what? Very, very high you to know for your exams. Right?

Again, this is a chromosome three problem, right? And I'm going to explain the eye and the brain, whatever. This is a chromosome three problem. It's allosomodominant inheritance again in a tumor surpressurgy. Are you noticing something here? I almost want to call this the tumor surpressurgy in podcast, but it's pretty high you to know this, right? Many of these mutations are in tumor surpressurgyns. When you have these tumor surpressurgy mutations, you're going to have crazy, crazy, crazy, crazy, crazy proliferation of tumors. Right? So the thing is, if you have this mutation in VHL, right? Then you're going to stop degrading H1 alpha, HIF1 alpha, HIF1 alpha, HIF1 alpha. And the thing is when you stop degrading HIF1 alpha, HIF1 alpha is a signal. It pretty much tells you about it that, oh, there's hypoxia here. Oh, no, there's hypoxia here. Right? And if your body thinks there's hypoxia there, then you're going to make a lot of angiogenic factors, a lot of angiogenic factors, angiogenic factors. And when you make all these angiogenic factors, you're going to make a lot of angiogenic tumors like what? Like hemangioblastomas. Like hemangioblastomas. So these people they tend to have hemangioblastomas of the cerebellum, right? Remember, typically this is going to be a mass in the posterior forza, typically in the cerebellum, right? And it's going to contain calcifications, right?

So if you see a mass that is calcified in the posterior forza on the USMD exams, think about a hemangioblastoma in a child. If you see a mass that is calcified and it's a super-tentorial mass and detail you that, oh, wait, this mass is in the, you know, it's a super-cellar mass. They want to be thinking about a cranial faring gym on that those are circumstances. But basically, these people have a lot of hemangioblastomas and you can have hemangioblastomas in the cerebellum. So the posterior forza, you can have hemangioblastomas in the retina. You can have hemangioblastomas in the spine, right? And the thing is these hemangioblastomas, they love to make evil in a parneoplastic fashion, right? They love to make evil in a parneoplastic fashion. That evil can cause polycyphemia, right? So that's something pretty high you do you want to know for your exams, right? And remember, what are some other things you may find in a person that has VHL? Well, this people can have bilateral, clear-celled retinal cell, carcinoma. Sometimes they can have fiochromocytomas. Remember, I said that it's one of those genetic diseases that has an association with a fio. Again, what are the diseases that have an association with a fio? Don't forget your Amyin tubes. Don't forget VHL. And don't forget NF1. Don't forget those three. Very important to know those for your test. All right.

And then they can also have like, you know, so they give you a question about a young patient that has a polycyphemia or has like multiple retinal cell carcinomas. They have a cerebellum mass. Think of VHL. Think of VHL, right? Don't be thinking of retinal cell carcinomas being spontaneous in a person that is like 15 years old, that's diagnosed with it. That's ridiculous, right? That's ridiculous. No. It should be in a person that is quite a bit older, right? Remember, the biggest risk factor for our RCC smoking, right? Well, you see like multiple retinal cell carcinomas in a very young person that presents a genetic disease, right? That presents one hip oil and that. Well, if you notice many family members, that's a lot of the way they can present it to your new exams. You see a person where many family members have retinal cell carcinomas. Think of that family having one hip oil and out disease because again, it's all those are more dominant, right? So obviously it's going to run in families. It's not necessarily going to skip a generation or anything like that. All right. Now, what if they give you a question about a child? And your told that this child, you know, is brought to the neurologist because he has been having multiple seizures, right? He has been having multiple multiple seizures, right? And you're told that he's in a special needs program, you know, at school, right? And then you're told that physical examination discloses hypopigmented skin lesions.

If you see something like this, what should you be thinking about? Well, I really hope you're seeing divine. This sounds an awful lot like tuberous sclerosis, right? Tuberous sclerosis. Tuberous sclerosis. Again, what's the skin on this disease? It's autozomodominant and it's in what kind of gene? In a tumor suppressor gene, right? You can have a TSE1 or a TSE2 mutation, a TSE1 or a TSE2 mutation, right? So what do these things normally do? Well, the thing is these things normally, the inhibit mTOR, the inhibit what? MTOR, M-T-O-R, the inhibit mTOR, right? So when you have mutations in these stains, mTOR is no longer inhibited. So you're going to have control growth of cells, you're going to have formation of hematomas, right? And the thing is, and this is in many different organs. You can form hematomas in many different organs, in many different organs, right? In many different organs. So if you see these hematomas in the brain, that's what usually causes the seizures and the intellectual disability that they get, right? You know, like tuberous in the brain. That's why it's called tuberous sclerosis, right? So what are the skin lesions I was talking about? Those are the ash leaf spots. Those are the hypo-pigmented molecules, right? They can have these things known as chagrin patches. They can have these facial angiophibromas, so like vascular like tumors on the face, right? Now in terms of the heart, remember they can have a cardiac ruptomioomas, right?

Cardiac ruptomioomas, it's actually like tumor you can find in the heart, right? They will try to trick you on your exams with cardiac mixoma, mixoma is not found on the USMLE's in tuberous sclerosis. It's cardiac ruptomioomas that are found in tuberous sclerosis, right? And then if they tell you that they have like flank pain, or like back pain, or they have hematuria, then you want to think about the renal angiomayo lipomas, angiomayo lipomas, right? It's a renal tumor that contains blood vessels, contains muscle and contains fat, right? Angiomayo lipomas, angiomayo lipomas, right? Those are the classic associated tumors, right? So you can keep that in the back of your mind for your exams. Now, what if they give you a question about a person, you know, like a lady or they tell you that, oh, in this family, they've noticed that they have a lot of early onset breast cancer, early onset leukemia, right? Early onset, like soft tissue tumors, like all these sarcovas. If you see something like this, I want you to think of a person having a p53 mutation, right? Think of a person that has a p53 mutation. So what are the four classic associated cancers with a p53 mutation? Because I don't know for whatever reason, resources don't just talk about this very much, but it's actually pretty high to know for exams, right? Think of breast cancer, think of leukemia, think of adrenal cortical cancers, right? So cancers of the adrenal gland, and then soft tissue sarcomas, right?

So breast cancer, leukemias, sarcomas, right? And the adrenal corticula tumors, right? The way I remember this is the numonic labs, you know, getting labs on a patient. So the L stands for leukemia, the A stands for adrenal cortical carcinomas, the B stands for breast cancer, the S stands for sarcomas, right? You see those tumors running in families, showing up really early in life, think of a p53 mutation, right? Again, autozomo dominant, right? In a tumor suppressor, you know, what's the disease I'm referring to here? I hope you're saying, ooh, divine, okay, this has to be leaf from an eye, which exactly is. This is leaf from an eye syndrome, leaf from an eye syndrome, right? Leaf from an eye syndrome, it's a p53 mutation, right? And many people know p53 has the guardian of the genome, right? The guardian of the genome. The thing is, whenever you have a p53 mutation, right, you're going to have abnormal cell cycle arrest, right? You're going to have, you're going to not be having a poptosis after DNA dummy, because remember, whenever you're doing the cell cycle, and your body notices that, oh shoot, it seems like there is DNA damage or whatever, you're not going to progress in the cell cycle, you're going to arrest the cell cycle. That cell is going on the way poptosis, but if you have a p53 mutation, your body is going to be like, eh, we have this DNA mutation, who cares, it's not a big deal, let's keep going, right?

The cell cycle will progress when it should not, the cell will keep leaving when it should not, you won't have a poptosis, right? And that's going to cause problems. Again, remember that lopsidomonic for the tumors that they get, right? So if you notice a person developing many of these cancers that I'm talking about, usually before like ages 30 to 40, think of leaf from an eye syndrome, think of leaf from an eye syndrome, right? Think of leaf from an eye syndrome, all right? And again, remember, you need two mutations to have this problem, right? You need two mutations to have this problem. Let me just kind of develop that point a little bit because it's something that is actually pretty high to know for you exams. So the thing is, when you, you know, it kind of follows the same thing as a like retinoblastoma, right? So the thing is, these tumor suppressor genes, right? Obviously we're deployed organisms, right? So we have two copies of these genes. The thing is, if you have a mutation in one copy, it's not a big deal. You know, you're not going to have problems, right? Because you still have one normal copy. That one normal copy is producing enough tumor suppressor protein. So you're not in trouble, you're fine. But so your heterozygous for the mutation has to start, right? Your heterozygous. But when the second, because the gene is expressed in an ozone-dominant fashion, right? So if you have one good one around, it's not a big deal.

But once the second one is mutated and then you become homozygous for the mutation, then you have no tumor suppressor gene products, then you're going to get in trouble. That genetic phenomenon, they love to test it on the USML exams. It's called a loss of heterozygosity, a loss of heterozygosity. When you lose heterozygosity, then you start getting in trouble. You start getting in trouble, right? So pretty, pretty high yield to know that for your exams. So don't forget, leave from an eye syndrome, P53 mutation. Now, what if they give you a question about a person that, you know, she's age 30, she's diagnosed with like ovarian cancer, right? Diagnosis of ovarian cancer, right? And they tell you that her mom died of brisk cancer, of invasive brisk cancer at age 35. When you see something like this, what should you be thinking about? I hope you're thinking about brachamutations, right? Brachamutations, right? You know, bracha 1, bracha 2. And let me say something here. Again, autism, ovarian, tumor, suppressor genes. But there's some kind of funny things our friends at the NBM love to do with these people. That is actually pretty high yield to know. So the thing is, they know that many of you can recognize the term bracha pretty easily, right? Many of you can recognize the term bracha pretty easily. So do you know sometimes what they do on the USML exams? One thing they do sometimes these days is that they will call it the hereditary breast and ovarian cancer syndrome.

Hereditary breast and ovarian cancer syndrome. If you see that term, that's just a fancy term for brachal ear exams. Just keep that in mind. Now remember, we can have mutations in bracha 1 and bracha 2. Bracha 1 is a mutation in chromosome 17. Bracha 2 is a mutation in chromosome 13. So 1 for 17, 2 for 13. Is there another disease we've talked about where the mutation is in chromosome 17? And F1, very good, and F1, right? So bracha 1 is a chromosome 17 mutation. Bracha 2 is a chromosome 13 mutation. Again, these are both chromosomal dominant disorders, right, in tumor suppressor genes, right? And what do these things do again? Remember for each of these things in this genetic sprint, I'm trying to give you some context on the genetic mechanism, right? Where necessary? There's one of these diseases where the genetic mechanism known, you know, you shouldn't care about those, they almost never test those, but there are many that they do test, right? Again, they know that many of you have in your on-key decks have memorized the chromosome, whatever. What do you know many of you don't understand or know is the pathway that leads to a tumor, right? So make sure you know these things, make sure you know these things, right? So these people, they have bracha 1, bracha 2 mutations, right? And those things are involved in double-stranded DNA break repair, double-stranded DNA break repair.

So think about it, if you mess up double-stranded DNA break repair, you're going to have lots of problems with tumors. And is there another genetic disease you may want to know for your exams? That's associated with issues with double-stranded DNA break repair. I hope you're saying, oh, divine, etaxialinjecthesia, etaxialinjecthesia is also an issue with a double-stranded DNA break repair, right? So what are some other kind of high yield things to know here? We'll remember BRCA 1, it carries a high risk of ovarian cancer, right? It has a higher ovarian cancer risk compared to BRCA 2. Sometimes they test some of these strange epidemiologic facts with these BRCA mutations, right? So don't get me wrong, BRCA 1, BRCA 2 can both cause ovarian cancer, but the one that carries the higher ovarian cancer risk is BRCA 1, BRCA 2 has an association with modules, breasts, and ovarian cancer, but it's also a video with like pancreatic cancer, in fact when people are diagnosed with BRCA mutations, they do need to be screened for pancreatic cancer, right? And also male breast cancer, you see a man, the husband breast cancer, that one has to be screened for BRCA 2 mutation, for BRCA 2 mutation, right? For BRCA 2 mutation, right? And one thing that you should know is that these people start getting screened for BRCA 2, 25. Starting at age 25, you're going to get anobrace them, our eyes, right?

Anobrace them, and then when they get to age 30, they're going to get anobrace them, our eyes, and mammograms, anobrace them, our eyes, and mammograms, right? We don't start the mammograms until they heat each 30, right? So again, if you see a strong family history of early onset breast cancer, early onset ovarian cancer, across many generations, think of again, here at age 3, breast, an ovarian cancer, syndrome, super, super high up to no for your exams. Now, one thing I'm just going to say that you should know here, for these people in terms of treatment, there are these groups of drugs known as the PARP, P-A-R-P inhibitors that are helpful for these people. It kind of exploits the pathway that is messed up in people that have BRCA mutations. That's about as far as I'm going to go here in terms of PARP inhibitors. I'll probably talk about it in more detail in a future podcast. And then the last disorder we'll talk about on the exams is, so what if they give you a question about a child? And you're told that this child has been completely over a very significant bone pain, right? Let's say it's a 13-year-old child, completely over a significant bone pain in the right lower extremity, in the right lower extremity. And then you're told that this child has, you know, has a severe short bowel syndrome because of extensive uh, extensive resection of the presence had a procedure where the bowel was extensively resected a few years ago.

If you see something like this, think of FAP, right? Familiar at the NUMITOS polyposis, right? Remember, this is an APC mutation chromosome five, or the ZOMO dominant disorder, right? And again, this is in a tumor suppressor gene, tumor suppressor gene, right? So what does APC normally do? Let's do the cell biology integration here. Normally, it decreased something in a beta-cutting. I'm pretty sure I did research on stuff like this like back in the day in college or something crazy, I think, right? But it decreased beta-cutting, right? Now the thing is, when you are not able to degrade beta-cutting, so C-A-T-E-N-I-N anymore, then you're going to have crazy, crazy, went signaling, W-N-T signaling, right? And the thing that's going to happen as a result of that is that your colonic epithelial cells, they're going to proliferate like crazy, right? So these people are going to have like thousands of colonic at a NUMITOS polyps, and those things can become cancers, especially when you're throwing a care-as-matition on top or a P53 mutation on top, and that can get you in trouble, right? So for these people, colon cancer is pretty much inevitable, right? If you don't do a collecting, if you don't do a collecting, that's why this person in this question has a short bowel syndrome, right? So remember, why do they have this right low extremity pain? It's because they have a Gardener syndrome. Remember Gardener syndrome is when you have FAP, right?

And you have like osteoomers, you have like these soft tissue tumors, like osteoomers, desmoid tumors, epidermal cysts, and things like that. If you see a person that has FAP and they have brain tumors, think of TORCO, I mean, sorry, I think of TORCO syndrome, T-U-R-C-O-C-O-T, right? Remember, these people generally they need colonoscopies starting at each 10, right? Starting at each 10, they need a colonoscopies just because of all these problems that they can have with colorectal cancer, right? Remember, these people, prophylactic collectumies, are recommended once you confirm that they have this disease because again, it's not a matter of if they're going to develop colorectal cancer at some point in their lives. All right, so I think this has kind of gone on for long. So again, there's going to be another part. It's actually a pretty high yield series, but just some of the things I want to talk about, but these are easy points on the exams if you know these things. And if you love the way I teach, you love the way I make integrations, you're going to love my classes. I'm going to have having a bunch of classes that start not next week, but a week after next. I have a CCS KCS class. It's a one-hour class. I have a testing strategy class that's two and a half hours long, biostat class that's four hours long, and social sciences quality improvement, healthcare systems, and a class, an ethics class. That's a five-hour class.

These four classes, the first one, the CCS class overseas for step three. But the other three are for step one to three. And then beyond that, I have a last minute review for step two and step three, that's three hours long, and then have a 20-hour step two, step three class. Many people have taken these classes and don't extremely well on the exams. I've literally got in an email, I believe, from somebody within the last two or three weeks that took one of my classes and got like almost like, got in the high two seventies, right? So my classes are very well validated. They're very well put together classes, right? They prepare people really well for the US Emily exams. So if you're interested, shoot me an email that can give you some more information. Also, if you're one or one children for the US Emily and complex exams, and I help with error's applications as well. So if you're interested in any of these things, shoot me an email that can give you some more information. And I have these podcasts on Apple Google on Spotify, I have a You Tube channel, you can check out as well. And then I have another website called, divininterventionlifelessons.com. Divininterventionlifelessons.com. Many of you know I'm a Christ follower, so every week, I post like one podcast from a biblical perspective address a life lesson. There's actually an Apple podcast associated with that called the Divininterventionlifelessons podcast. So thank you for listening to me today.

I will see you go to Berlin in episode 663 of a wonderful day. God bless you and bye for now. Thank you.

Café-au-lait spots, neurofibromas, and Lisch nodules (iris hamartomas).

VHL (Von Hippel-Lindau disease), located on chromosome 3.

Mutation in the APC gene, leading to defective $\beta$-catenin degradation and excessive WNT signaling.

Cardiac rhabdomyomas and renal angiomyolipomas.

BLASS (Breast cancer, Leukemia, Adrenal cortical carcinomas, Soft tissue sarcomas).

Neurofibromatosis Type 2 (NF2).

Chromosome 17.

MEN2, VHL, and NF1.

The mTOR pathway.

Vestibular schwannomas and meningiomas.

Familial Adenomatous Polyposis (FAP).

Bilateral clear-cell retinal carcinoma.

Chromosome 17.

MEN2, VHL, and NF1.

The mTOR pathway.

Vestibular schwannomas and meningiomas.

Familial Adenomatous Polyposis (FAP).

Bilateral clear-cell retinal carcinoma.