DIP Episode 661 - The Genetics Sprint (for Step 2 and 3) Part 1

All right, welcome. My name is divine. This is episode 661 of the divine intervention podcast. And to this podcast, I'm going to call this the Sprintin through genetics. Sprintin through genetics. We know that genetics is something that pops up on the US Emily exams, right? A lot on step one, but definitely on step two and step three as well. So I want to kind of spring through the key things you need to know for most of the high-yield genetic diseases. So this would be one of those things where you're like, I just want to quick and dirty review of genetics for step two and step three. This will be a very good primer for that kind of situation. So first thing, what if they give you a question about a child, right? And the tell you that this child is like 15 years old and you're told that he has a history of recurring respiratory infections. And then you're told that, you know, for the last two days he has been having high feverers, he has been having shortness of breath. And then they tell you that you listen to the lungs and you hear decreased breath sounds on the right side. And then they tell you that a sputum sample is obtained. And then they'll ask you like which of the four is the most likely finding on, on, you know, with a gram stain of a sputum sample specimen, right? And you know, they will tell you something about like a histrogmal absorption or whatever. And I really hope you're saying that, hey, I'm going to find like gram positive cox I, right?

So this person has cystic fibrosis, right? So remember cystic fibrosis arises from a CFTR mutation, so I'm coming from seven is a little more recessive, right? And as many of us know, I'm going to explain the findings for this question. The Delta F50 E deletion is the classic mutation, right? Basically, the pathophase there is that you have this misfolded protein, right? And he basically gets degraded before he even reaches the membrane of the cell, right? And then if that happens, chloride, bicarb is not going to be transported well. Many people just memorize like the chloride transporter issue with the CFTR transporter. But one thing people don't realize is that bicarb is also not transported well. That's actually kind of important to know for you exams, right? So these people, they have like very thick sputum, very thick secretions. So that causes them to have recurrent infections with staphores, for example. Remember staphores is the most common cause of pneumonia in CF patients that are less than 18 years, less than 20. Once you get past these 20s, it's going to be pseudomonas, right? So if it was a low-bar pneumonia and they were asking for the expected sputum sample results for a person over 20, they want to be thinking along the lines of a gram negative, right? That's pseudomonas. But here, the person is under 20 that I described in the vignette. So it's going to be a gram positive coxine, which is how staphore is is, right?

I remember both of the Halsistic fibrosis, many times they'll have like diarrhea, right, from phatmal absorption, right? Because they have a pancreatic insufficiency, lipase is not being released. So because lipase is not being released, they're not able to emulsify phat and digest phat, right? So they have like a phatmal absorption, right? And then remember, they can also have like a meconium ilius, right? As neonates, you notice that while they've lived for more than 40 hours and they've not, they've not pooped. So how do we diagnose this? Remember, again, we diagnose this with a sweat chloride test. It's going to be elevated, right? And you're going to notice that the newborn screen, part of the newborn screen, actually, that we screen, the things we screen for we, we check that serum, immunoreactive, atrop synogen, right? So again, you see a child, you know, in addition to the vignettes I've presented, but you see a child that is, or not even a child, it can be a male that is infertile. And then they tell you that, oh, that there's a bilateral absence of the vast difference on, on diagnostic testing. Think of the CFTR, mutation, right? Think of cystic fibrosis. All right. Now, what if they give you a question about a patient? And they tell you that this patient is from an African country, and you're told that, he has a history of just, you know, that he was adopted and his birth history was unknown. And you're told that he has a history of chronic fatigue.

And then now he presents with very severe pain in his, in his extremities. And then you're also giving like some labs. And you notice that he's hemoglobin is 8.2. And he's MCV is 85. So it's a normal seric anemia. And then you're also told that all that, you know, over the last year, he has had two episodes of an omochocone pneumonia that I've required antibiotic therapy. Well, if you see something like this, I hope you're thinking of a person having sickle cell disease, right? Remember sickle cell disease, just like cystic fibrosis is a rosomal recessive, right? Remember, cystic fibrosis was a chromosome seven problem. Sickle cell disease is a chromosome 11 problem, right? Basically, it's a single point mutation, right? Glutamic acid is replaced by V-line at position six, right? Of the beta-globing chain. And the thing is in hypoxic environments, there's hemoglobin S that is formed, right? The oceanithet hemoglobin S, he likes to form polymers. And the thing is, those polymers are the things that then cause the red blood cell to sickle. That's what causes the red blood cell to sickle, right? And then those things are also very adept at occluding vessels. So you're going to have like visual, inclusive crises, you're going to have extravascular hemoluses in travascular hemoluses, right? And remember, over time, these people are going to auto-infarct their spleen, and as the spleen gets auto-infarcted, right? They're going to start struggling with encapsulated organisms.

Remember, strep pneumo is an encapsulated organism. So these people, they tend to have various infections within encapsulated boxes, right? So like strep pneumo, HM fluenza, niceramidin, gildedis, and things like that, right? And then remember, if they give you a question about a person that has sickle cell disease, and the person has hip pain, what should you be thinking about? Well, I really hope that you're thinking about some kind of osteonecrosis, right? Some kind of evasculinecrosis of the femoral head, right? If they describe a person that has sickle cell disease, and they have like very severe chest pain and all those things, like very severe chest pain, and they tell you that chest radiography shows like pulmonary infiltrates, and hope you're thinking about a huge chest syndrome, right? Remember, typically for those, you're going to do some kind of plasma, plasma exchange, right? You're going to do some kind of plasma, plasma exchange, right? And they can have all these visual-aclusive crises. Remember, give those people opios for those visual-aclusive crises, right? Now, one thing you just want to keep in mind with this African association that I mentioned at the beginning is that people that I had a rosygot, right? People that have sickle cell traits, right? They tend to actually get protection from plasmodium, fausiproma, maliria, right? It's just one of those strange associations to know for you exams.

And if you ever see hematuria in a person that has sickle cell disease, the thing you absolutely want to think about is renau-populary necrosis, renau-populary necrosis, renau-populary necrosis, right? And they remember, also, my life is in sickle cell disease going to be caused by someonella, right? Now, what if they give you a question about a child? And you're told that this child, you know, has a history of just chronic weakness, uh, office, you know, chronic muscle weakness, and then you're told that over the last, you know, past year, he has been having progressive shortness or progressively worsening shortness or breath. And they tell you that when you listen to his lungs, you can hear crackles, right? You can hear crackles. And they tell you that imaging shows bivine, echocardiography shows like bivine, chocolate dilation, right? And then we're told that again, he has a lot of proximal muscle weakness and you're told that he has very stoutly defined lower extremities. If you see something like this, what should you be thinking about? I hope you're saying divine. This sounds an awful lot like DMD, like the Shane muscular dystrophy, right? Remember, this is an excellent, recessive disorder. So it's highly likely to show up in males on your exams, highly likely to show up in males on your exams, right? Remember, what's the pathophase, right? It's a frame shift deletion guys.

As you see me emphasize the specific pathophysiology behind some of these genetic syndroms, make sure you know them for your exams. Right? So it's a, it's a single, it's a frame shift deletion, right? And that basically causes you to have like complete absence of dystrophy. You want to be able to compare this with beckers muscular dystrophy where it's more of an inframutation, right? So you'll form dystrophy that has partial function in beckers. You'll form no dystrophy whatsoever in the Shane's, right? And generally again, we're going to see the boys is going to, you know, they're going to start having symptoms very early in life. You have a lot of proximal weakness, which is indicative of my apathy, right? Remember, whenever you see proximal muscle weakness, you think of a myapathy and they're going to have gourd signs, right? You're going to basically use your arms to walk up the body for you to stand, you know, from like a seated position or from being on the ground, right? And the thing is, you know, what's the mechanism behind those stout limbs that I described in the vinaig that I gave? Well, it's this thing known as a caustodohypertrophy, right? So the thing is instead of muscle, like the muscles, their muscles can get replaced with fiber fatty tissue, like a lot of fiber tissue, a lot of fatty tissue, right?

And many times you're going to notice in the question stem that these people are going to have a very high creatine kinase, the ack is going to be elevated, right? Now, why did I talk about the crackles and what not? Well, this person has the elithid cardiomyopathy. Remember, the elithid cardiomyopathy is actually the most common cause of death in these people. In fact, our friends at the NBM Es can give you a question about a person that has de chez muscular dystrophy and ask which of the following screening tests should be conducted at this time? Pick the answer choice that talks about echocardiography because you want to screen them for the elithid cardiomyopathy that is characteristic of that disease, right? And then, what if they give you a question about a patient, right? And they tell you that this patient has had, has been seen a lot of inappropriate things in recent times. He's a 37 year old male. And then they ask, you know, he has been saying, you know, just very strange things. He has been having unusual, they tell you that his wife brought him to the physician because he has been having like unusual movements of his extremities. And, you know, that he's been having, that he has been very depressed, right? He has been very depressed, he has become very forgetful. If you see something like this, I hope you're thinking about haunting things, right? The thing is our friends at the NBM Es they recognize that it's super easy for many people to recognize haunting things.

So sometimes they like to ask surrogate details about haunting things, right? So like, for example, they can ask you which of the following would most likely be observed on brain imaging in this patient, right? You want to pick the answer that talks about like echocardiography, right? And you're actually going to have dilation of the frontal horns of the lateral ventricles. That's a very high youth thing to know. Dilation of the frontal horns of the lateral ventricles, dilation of the frontal horns of the lateral ventricles, right? So what's the deal with haunting things? Disease, I remember it's a trinocrythia repeat disorder. The here, the problem is in chromosome four, right? So the sumo dominant, you have these C.E.G. trinocrythia repeat, right? And some key things that they love to test with this is that, you know, you're going to have this issue of anticipation, right? So they can even ask you something about, because remember our friends at the MBM is the love prognosis prognosis prognosis these days on the US Emily exams. So they can ask you about the prognosis of his future offspring. Their prognosis is going to be worse. And they can ask you about the mechanism behind the worsening of the prognosis. You want to talk about, you want to pick an answer choice that talks about an expansion of the trinocrythia repeat, right? So that's the genetic principle of anticipation, right?

Basically as the expansion worsens, the thing that's going to happen to these person's kids is that you're going to have a worse disease. You're going to have earlier presentation in successive generations, right? Especially when you get it from your dad, right? Especially with paternal transmission. Just one of these kind of strange things you need to know for your, for your exams, right? So again, what's the pathophase? The pathophase here is that you pretty much have a gain of function mutation, right? And in the haunting gene. And as that happens, you're going to have the death of neurons in the codi and in the puttamin. So it's not only the codi that is messed up. Again, our friends at the NBA is no, hey, codi, codi, hydrophic, codi, hydrophic, codi, hydrophic, make sure you know these other strange things I'm talking about, like lots of neurons in the puttamin. That's pretty high up to know for your exams. Or, you know, almost like a hydrocephalus X-Vaco that we see with the frontal horns of the lateral ventricles, right? So again, remember, they're going to have choriform movements. They're going to have all these psychiatric problems. They can have like, they can make a haunting gene question like a depression question, right? A psychosis question and things like that. Right? And then they're going to have like progressive dementia. Keep that in the back of your mind for your exams. And we're going to manage it typically with tetrabency. Right?

Now, what if they give you a question about a child, right? You have this, you know, this child is coming for his three month appointment. You will be told that the mom had proprenate ocar, deliver the child at home. And this is her first physician visit, her first pediatrician visit. And you're told that the child has like this long narrow face, very large outward facing ears. So these large inverted ears, right? And then you're told that you can hear a holosis, stoic murmur at the at the fifth intercostal space in the left mechlavicular line. Well, if you see something like this, I really hope you're saying that divine. This sounds a lot for Lord like fragile X syndrome, right? fragile X syndrome. Remember, it's an it's a triglytheraepid disorder as well. It's a CGG triglytheraepid. It's excellent dominant, right? It's excellent dominant. That's pretty high yo to know for you exams. And the genetic mutation is in the FMR1 gene, right? But basically, what's the pathophys behind fragile X syndrome? Well, the thing that happens is you actually don't have a structural protein defect, right? You actually do not have a structural protein defect. The thing that happens is when you have this triglytheraepid issue, you're going to have hypermethylation and silencing of your genes. Remember, one of the ways we silence our genome is by methylation, right? So you pretty much have hypermethylation, you silence your genes. When that happens, then you're going to be in trouble.

You're going to be in trouble. You're going to be in trouble, right? You're going to be in trouble. And this is one thing that they like you to know with regards to epidemiology, right? So the thing is this is actually the second most common genetic cause of intellectual disability. It is the second most common genetic cause of intellectual disability in kids, but it is the most common heritable cause, right? So you maybe won't define what is the most common genetic cause of intellectual disability. It's going to be Down syndrome. Down syndrome is number one, but remember, Down syndrome is not heritable. It's not heritable. It's a genetic problem, but it's not heritable. But fragile X syndrome is a genetic problem and it is heritable. So fragile X syndrome is number two in terms of genetic causes of intellectual disability. After Down syndrome, but it's number one in terms of genetic syndrome causing intellectual disability that are heritable, that are heritable. Okay? This is a classic error that many people make on the exams. So sorry, let me just kind of say something, just an off-short point and then I'll come back. I promise to fragile X syndrome. For example, let's talk about brain cancer, right? In kids, the most common primary brain tumor in kids is a Pylocytic Astrocytoma, right? Number two is a Medulloblastoma. But Medulloblastoma is number one in terms of malignant primary brain tumors in kids because Medulloblastomas can spread.

They can spread through CSF pathways from the brain to the spinal cord, right? So just going to keep that in mind. All right. Now, classic things you're going to see with a fragile X syndrome, right? You're going to see a long narrow face, right? Large outward facing ears. Sometimes you may see them use the term everted ears, right? And many times these kids will have a, especially after the heat puberty, they're going to have macros or kitties, and they're going to have very big testicles. So the thing is those big testicles, you may not see those early in life, but as the heat puberty, you're going to see those big testicles, right? And then that memory, described as the memory of my trova, my trova of prolapse, right? Very, very common in kids that have very, very common in kids that have a fragile X syndrome, right? And remember, you can also see this whole generic anticipation problem, right? Especially when you get the mutant X chromosome from mommy, from mommy, from mommy, from mommy, okay? So remember what I said about haunting things. I said that haunting things, generic anticipation tends to be more pronounced when you get the defective gene from your dad. But for fragile X syndrome, the problem tends to be more pronounced in terms of anticipation when you get the bud gene from your mom. That's pretty high you to know for your exams, right? So mom for fragile X dad for haunting things, mom for fragile X dad for haunting things, okay?

That's really high you to know for purposes of your exams. And then remember, poor dad have a fragile X can also have a lot of gird, right? That's actually one of the most common GI disorders in those folks. And then what if they give you a question about a child, right? And they tell you, actually, like, you know, they give you a question about a person that has a, uh, Marfan syndrome, right? And then they ask about what is the most likely cause of mortality in this patient, right? What is the most common likely cause of mortality in this patient? I really hope that you're going to pick an answer that talks about like erotic, something related to the erotic, right? The thing is, Marfan's is something that is probably in every on key deck known to mankind, right? Probably in every on key deck known to mankind. But the thing is for purposes of the USMLE exams, we really do expect you to know a lot of surrogate things about Marfan syndrome, right? So remember, you know, the heart problems are the things that basically kill these people, right? You know, they have like dilation of the erotic roots, they can have erotic dissection, right? They can have mitral valve prolapse, right? Remember, what's the other disorder we've talked about so far that has MVP? It's going to be what? Fragellex syndrome. It's going to be fragile, fragile X syndrome, right?

In fact, because of all these heart problems that these people with Marfan's can get, we tend to get echocardiograms on these people freely frequently, right? Fully, freely frequently. So I didn't know that for your test. So what's the pathophase behind for Marfan syndrome? Remember, it's going to be a Fibrillian 1 mutation, right? It's going to be an FBN1 mutation, chromosome 15, right? It's a rosomal dominant, right? So the thing is when you have this defect in Fibrillian 1, elastic fibers are not going to form very well. You're not going to form good elastic fibers, right? And then you're going to have increased TGF beta signaling, increased TGF beta signaling. Again, the USMLE is they know that you know most of what you need to know about Marfan's, right? So again, they start going after these offshoot points, right? So again, they can give you a question about Marfan's. You're reading the question, you know that this is a definite Marfan's question. And then the right answer ends up being increased TGF beta signaling, or the right answer ends up being impaired elastic fiber formation, right? The thing is many questions on the USMLE's days, these days don't have direct answers. The answers that they promote, answer choices that describe things instead of give you direct things like, oh, like you read the question, you see the answer that says Marfan's. No, those things that become a rare and rare on the USMLE exams.

Now, remember, what are some classic findings in these folks, right? You're going to have like very tall stature, they're going to have a ductile right, you know, with your, with your digits, they're going to have vectors, these deformities, right? So they can actually give you a restrictive long disease question in a person that has a Marfan syndrome, right? Because the thing is when they have those vectors deformities, one thing that can happen is that it can actually make your chest wall, you know, you know, they can have chest wall problems that makes it hard for the lungs to expand, right? And if the lungs cannot expand, you're going to have a restrictive picture of long disease. So typically that's going to be associated with a normal DLC, right? And a normal A grade in, because the lungs don't have any problems. It's just the area around the lungs, the lungs can not seem to expand very well. So that's why they have restrictive disease. That's why they have restrictive disease, right? And again, remember, for people that have a Marfan's, again, don't forget the, the heart problems, right? The mitral valve prolapse, the uric road dilation, the uric dissection, right? And remember, these people will typically have an upward lens dislocation, right? So it's going to be super-otemporal, right? Super-otemporal, right? Contrast this with a person that has a downward dislocation of the lens, which we find in a homocystinory, right?

Again, that open out in Marfan's versus down and in in a homocystinory. Again, they may use, again, usual terms, right? Like for like Marfan's, they can say super-otemporal, right? So just going to keep that in mind. You see the terms super-otemporal, think of Marfan's syndrome, right? Now, what if they give you a question about a child that has, you know, the tell you that he's joined some very mobile, right? And that this child, you know, he's parents have restricted him from playing because he tends to get a very significant, very significant injuries that are very difficult to heal whenever he plays with his friends outside, right? And they tell you that all that this child has very, or physical exam, the child has like soft, velvety skin. If you see something like this, what are you thinking about? Well, I'd really hope you're thinking about a Elasdanlos syndrome, Elasdanlos syndrome, right? So remember, Elasdanlos syndrome, there's two types, right? There's the vascular type and then there's the classical type, right? So what's the pathophys? And these are both autosomodominant, you got to know that for your exams. So what's the pathophys here? Well, the pathophys here for the vascular type is that you have a type three collagen problem, right? So the musician is going to be in a C-O-L-3-A1, C-O-L-3-A1, right? When you have that vascular type, you're going to have like very fragile arteries, you're going to have very fragile organs, right?

So the thing is, these people actually have a super high risk of like rupture of arteries, right? Or they can have like bowel rupture, they can have like urine rupture, right? So like for example, if a person has Elasdanlos, it's probably not a bad idea for those people to do a scheduled C section instead of going into labor. You don't want those people to go into labor because the uterus can literally explode, right? That's not a good thing, right? Or if you see like severe, sodium onset abdomen opening, a person that has a histroveralusdanlos and then they tell you about free-earned diaphragm, right? Or the person has like signs of periodo 90s and you know, bowel rigidity and things like that. You probably want to think about the person having some kind of bowel rupture, right? So they can have like a teor rupture, right? That's what can cause them to have like urinary dissection. They have like a teor rupture, they have a urinary rupture, so kind of keep that in mind. And then the classical type is a C-O-L-5-A1 mutation. So guys, be careful, right? So C-O-L-3-A1 is the vascular type. That's a type three collagen issue. C-O-L-3-A1. The classical type is C-O-L-5-A1, right? That's the one that gives you like the hyperextensible skin, the joint hypermobility, the easy bruising and things like that, right? And the thing is, again, they may try to stay away from the word hyperextensible skin on your exams.

Instead, they may tell you that the person has very soft skin, very velvety skin. If you see something like that, you really want to think about a person having a Elas Danlos syndrome, right? So the thing is, these people, they have ones that are very difficult to heal, right? And many times when he heals, you're going to have like these, almost like sometimes on exams he may describe it as a cigarette paper scar, a cigarette paper scar, right? So one thing I just want to mention here before I move to the next disorder is, please, do not conflict Elas Danlos syndrome with morphans. This is a common error people make on the exams, right? Many people think that morphans is a collagen problem. No, morphans is not a collagen problem, right? morphans is more of a fibrilline. It's a connective tissue scaffolding problem. It's a connective tissue scaffolding problem, right? Elas Danlos on the other hand is an actual bona fide collagen problem, an actual bona fide collagen problem. Right? Now, what if they give you a question about a patient, right? And you're told that this patient, you know, is brought to his four-year-old boy, he's brought to the emergency room by his parents because he has been clutching his left, you know, his left low extremity for the last, you know, like four hours, and then you're told that all that they do a skeletal survey and they determine that all this child does have a fracture.

And then they tell you that this is, this child has had a multiple similar presentations in the past as well for, you know, fractures. And then they will try to throw you a smoke screen answer to kind of mess you up about picking something with a colon CPS or whatever child protective services. But the thing is, in addition to that, they will give you some stuff in the question that talks about like the person having like blue scleror or whatever, right? Whenever he sees something like, and then they can tell you that the child, you know, that the child seems oblivious when he's called by the physician or whatever. Whenever he sees something, and you know, they can even tell you something about like dental imperfections on a physical exam. Whenever he sees something like this, think of osteogenesis imperfecta, right? Think of osteogenesis imperfecta. If you notice for this, for this podcast, I'm trying to hit on the important high old things, but I'm also trying to emphasize some of the unusual things that you may not see mentioned in many resources was kind of high to know for your exam. So let's talk because this is another collagen issue, right? So osteogenesis imperfecta. So remember, it's a COL-1 A1 mutation or COL-1 A2 mutation. So it was a more dominant, right? So remember, we talked about Elastanlo's vascular kind, that's COL-3 A1. That's the vascular type, classical type, COL-5 A1. Okay, now look at this. Osteogenesis imperfecta, COL-1 A1, right?

It's a type 1 collagen problem. I'm like, Elastanlo's, that's a type 3 and type 5 collagen problem. So COL-1 A1 here or COL-1 A2, so the problem here is that type 1 collagen is not made properly. So you literally have defective type 1 collagen synthesis, right? And the thing is, basically, most of these kids is more like just a quantitative reduction in how much type 1 collagen they're making, right? Most is not that they have like no type 1 collagen at all. If you have no type 1 collagen at all, that's really bad, right? So most times they will have type 1 collagen. They're just not making a none for it. They're just not making a none for it, right? So you're going to see like a lot of fractures, minimal trauma, right? And they will try to get you thinking about child abuse, but it's not child abuse, right? So just be careful about that, right? Now, because remember, type 1 collagen is found in bones, right? So you're going to have a lot of fractures with minimal trauma, right? And then remember, blue sclery, blue sclery, blue sclery with this stuff, right? So now what's the mechanism behind the blue sclery? Because again, they can give you, they can say, which of the following most likely explains the ocular finding in this patient. Again, the USML is these days, they have very big on pathophysiology. Remember, the blue sclery is because the person's sclery is very thin, right? It's very thin, right? To make your sclery, you do need type 1 collagen for that, right?

But if you don't have enough type 1 collagen, your sclery is going to be very thin. So the stuff that's underneath the sclery that normally you should not be able to see, you end up seeing, right? That very thin sclery is going to make it very easy to see that on the line coroid. So it's enhanced visibility of the underlying coroid layer that is the mechanism behind the blue sclery in a person that has osteogenesis imperfecta, right? And remember, these people that have OI, right, they can have hearing loss, right? So keep that in mind because remember, your middle ear ossicles are literally bones, your maliosy or ecaz incas and your steepies, right? And remember, they can also have issues with their teeth, right? They can tell you some story on your exams about dental imperfections. If you see this, think about osteogenesis imperfecta. Think about osteogenesis imperfector. In fact, sometimes on exams, they call this a dintinogenesis imperfecta dintinogenesis imperfecta, right? And then just real quick, closely related to the soda, I'll talk about this and then I'll wrap up this podcast. I think I'll probably do a part two of this. I think this stuff is kind of high out for the exams, right? Again, you know, you're going to see these things tested, especially on the multi-systems processes and disorders because, you know, it's just a disparate series of things, right? But e-controplegia is the thing you don't want to mess up with osteogenesis imperfecta, right?

E-controplegia is also the zoom out dominant just like OI, right? And it arises from an FGFR3 mutation, FGFR3 mutation, right? So the thing is here, you have again a function mutation, right? So FGFR3 is constitutively activated. It is what? Constitutively activated. And when that happens, your condro sites are going to be proliferating like crazy. Your condro sites, right? Your cartilage forming cells are going to be proliferating like crazy. So the thing that's going to happen here is this child is going to have like very short limbs, right? But you'll have a normal size trunk, right? In fact, sometimes on exams, you may see this term, rhizomelic dwarfism, rhizomelic rhizomelic dwarfism, right? And you'll have like, you know, they'll have a, you know, macrosephalides, they'll have frontal bossing and things like that, right? So macrosephalides, frontal bossing, right? And the thing is most cases that we see here as spontaneous mutation, right? As spontaneous mutations. And because our friends at the NBM is they like risk factors on the exams, they can ask you about the most likely risk factor, think of increasing paternal age, right? So increasing paternal age is a high yield risk factor for this stuff. On like Down syndrome rates, increasing maternal age, that is a big time risk factor, right? And remember, these people that have a condroplizia, they're going to have normal intelligence, they're going to have a completely normal lifespan, right?

It's not a lethal skeletal dysplasia, they're going to have a completely normal age completely, so completely completely normal lifespan, completely normal intelligence. Also kind of, Marfan syndrome also, they also have completely normal intelligence, but they have Marfan's, they do not have reduced intelligence, they don't have intellectual disability like we find in people that have a homocysteinuria, for example, I remember homocysteinurus or those are more recessive, or like Marfan's that is autozomo dominant. All right, so I'm going to go ahead and stop here. Again, if you like the way I teach, you like the way I make integrations, you're going to absolutely love my classes. They study in the third week of this month, right? I made a separate podcast, right? Describe those, you know, the two and a half hour test taking strategies class, four hour biostatistics class, one hour CCS cases class, five hour social sciences, quality improvement, healthcare systems, hospital medicine class, and then I have a three hour last minute review for step two and step three, and the 20 hour pretty comprehensive review for step two and step three. So if you're interested in any of these classes, just shoot me an email, I can give you some more information. Also, four one on one tutoring and I help with errors, applications, more interviews, personal, students, and things like that. And then I have these podcasts on Apple Google on Spotify. I also have a You Tube channel.

You can check out where I post the videos that I make. And then I also have another website called divineinterventionlifelessens.com. Many of you know my Christ follower, so every week I post like one podcast where from a biblical perspective, I do address a life lesson. It's actually an Apple podcast associated with that called the divine intervention life lessons podcast. So thank you for listening to me today. I will see you God willing episode 662 to continue this series. Would have a wonderful day. God bless you and bye for now. Thank you.

A frameshift deletion, leading to a complete absence of dystrophin protein.

Staphylococcus aureus (Gram-positive cocci).

Marfan's involves defective Fibrillin-1 (a connective tissue scaffolding protein), while EDS is a bona fide collagen defect.

The caudate nucleus and the putamen.

For Fragile X, anticipation tends to be more pronounced when inheriting the defective gene from the mother (maternal transmission).

Vaso-occlusive crisis leading to intestinal infarction.

Hypermethylation and subsequent silencing of genes (though it's a trinucleotide repeat disorder, the resulting pathology involves gene silencing).

Type I collagen ($COL1 A1$ or $COL1 A2$).

Cardiomyopathy; screen using echocardiography.

Superotemporal lens dislocation (due to impaired elastic fiber formation); contrast with the downward/inferior dislocation seen in homocystinuria.

$COL3 A1$ mutation; this leads to Type III collagen defects and extreme arterial fragility.

Huntington's Disease (CAG repeat expansion).

Hypermethylation and subsequent silencing of genes (though it's a trinucleotide repeat disorder, the resulting pathology involves gene silencing).

Type I collagen ($COL1 A1$ or $COL1 A2$).

Cardiomyopathy; screen using echocardiography.

Superotemporal lens dislocation (due to impaired elastic fiber formation); contrast with the downward/inferior dislocation seen in homocystinuria.

$COL3 A1$ mutation; this leads to Type III collagen defects and extreme arterial fragility.

Huntington's Disease (CAG repeat expansion).