 So we'll just get started with the retina and systemic inherited diseases. There's another version of this like on the Moran core that I gave in person a couple of years ago, but I kind of, I wasn't that happy with it. I kind of felt like it was like the Cirque Traverse at Snowbird. So a little bit like too intense. So I tried to turn this from a black diamond into a blue square, more like the looped loop in mineral basin where you can just like look down at the black diamonds, but you don't have to go down anything really scary. So hopefully that'll that'll help because I think you just can't learn it all at once. So it's better to just start from the high yield stuff. The stuff that really sticks out that would come up on a test question or in real life. So if you guys like see something like, oh, I saw this on a test, but it's not in your lecture. Let me know because that might be something to add in here. So I just talk about how not to memorize things because when you look at this table from your BCSE on the left here, it's like incredibly overwhelming. It's just like trying to remember the names or learning how to recognize all the little brown birds. If you're a birder, it's not a good way to learn anything. So the best way to learn things is to try to group things in three to five. Try to do repetition with increasing intervals and try to explain why things happen. So humans can remember like three to four things. That's why, you know, a phone number has things grouped into like three and four digits. Unfortunately, primary children slash IC did not recognize this human limitation and they made their FID numbers have however many digits. That is all at once not broken up. So every time I have to read the FID number out loud for a time out, I get kind of stressed. Another principle for how to memorize things is to gradually increase the intervals. So at first, you might only be able to remember it for a day. But after a couple of repetitions that you can remember it for two days, then a week, then month, and that's how you kind of get things into your long term memory. I have this picture of a dog here because this is how I taught my dog to remember that vacuum cleaners don't kill you by gradually increasing the interval between vacuuming. And humans remember stories. So you remember the Lorax really well and that kind of, you know, the emotions of the story and the characters a lot better than if you were to read, you know, an article about how many acres of coniferous forests were eliminated, et cetera. So trying to make a story, whether it's a patient's story or the story of how the body works and why I think will really help you memorize these like really high yield things that come up on tests because they affect the eyes and the rest of the body. So we're just going to do like four different like phenotypes, so four different categories of how the eyes or how the retinas look. One is a retinal degeneration. Another is fundus hypopigmentation. Another is a cherry red spot or vessel tortuosity kind of group those together. And the last is myopia combined with retinal detachment. So I'll start off with a case. This is a patient that I saw recently, an eight year old developmentally delayed female. She's had nice dagmas since she was little. They got a brain MRI to work her up when she was a couple of months old. That was normal. And but she's really had a lot of trouble seeing in the dark. And now, you know, she just can't see if there's a nightlight on. She used to have all the lights on. And recently she's also been feeling her way down the stairs and running into things. Her mom thinks that this could be due to her vision and her medical history. She's also congenitally deaf, but she can hear some with hearing aids, but she speaks sign language and she also had a history of hypotonia from when she was little and she has developmental delay globally. The mom said, I knew something was wrong at six months when she wouldn't sit up. But the pediatrician ignored me. I keep bringing her to all these doctors that no one will tell me what is wrong. Like, they're all these things wrong with her, but no one's put the picture together. So I asked her if she'd ever had genetic testing and she didn't know. But anyway, the reasons for that we could get into later. All right. And this is her fundus photos. I'm going to start calling on you guys, OK, in rotating order. George, what's abnormal quickly about the fundus photos? In the upper part. So in the fundus photos, I just see some speculated like bony lesions, like especially in the periphery. Yeah, they're bone spicules in here, those black things. And then there's also some sort of lesion over the macula itself. Yeah, it looks like a fairly like well demarcated area of RPE atrophy that's kind of like because this part is like paler than the rest. And then is this OCT normal? No, I would say it's not. Seems like overall pretty atrophic and especially like in the. In the RPE sort of can't really distinguish like outer retinal layers at all. Yeah, normally we have like the RPE and Brooks memory kind of right next to each other. And I think here there's still a little RPE left. But here it's the RPE is gone, but Brooks membrane is still there. And we definitely don't see that, you know, we normally see that I SOS junction, a third line, you know, above the RPE Brooks. And then the other clue that things are atrophic, like you said, like thinned and is that there's a lot of hyper transmission. So we're just seeing the coroid right or the normal, especially in the middle where there's this atrophic lesion. And the optic nerves are elevated. I frequently see this in people with inherited retina conditions. I don't know if it's like a known thing, maybe pediatric neuropomologists could tell me sometime. And then this is her flicker. So basically it's a measure of cone function because you're stimulating the retina with bright flashes that are happening so quickly that the cones have time to recover, but the rods don't have time to recover. And the amplitude is just really small. So overall, it looks like in her center macula, things are not good. And that's where most of the cones are. And then this flicker is also indicating there's a problem with the cones. But these bone spicles out in the periphery, where most of the rods are and the fact that she can't see at night, indicate that she has a rod problem. So because rods help you with a vision in the dark. So what to do next, George, what do you think we should do? Genetic testing or RP or RP related sort of syndromes. Yeah, exactly. So so as you mentioned, RP or RP related syndromes, because some of them can affect things like not only causing a retinitis pigmentosa like appearance in the eyes, but they can affect hearing and development like she has. So that's our next phenotype. So some gross generalizations about the things that cause retinal degeneration and systemic problems is that they're almost always recessive because they tend to be like really pretty bad. So they wouldn't be passed down in an autosomal dominant fashion because many times like people don't make it to the age of reproducing because of all their health problems. The other explanation for why they're often recessive is that many times these are mutations in the proteins that are enzymes. So they're breaking things down. And a lot of times for enzymes, you just need a small amount of that enzyme to catalyze thousands of reactions. So usually having half of the amount of enzymes because you've got like a dominant mutation with one good, one bad copy, one good copy, usually that wouldn't cause disease. You'd have to have like no enzyme at all. And then the other gross generalization is that most of these diseases have severe neurological problems, whether it's like on the developmental delay spectrum or they can even cause like progressive degeneration and death where kids like lose their ability to walk, talk, swallow, etc. So I like to categorize these by like what causes them. And by the critical like organelles in the in the photoreceptors. So this is the picture here. What do you think are some categories of diseases by organelle? Can you let's see, let's call on. Is it OK to call on the med students? You think this is a med student appropriate question? Where are you, Nana? Chase is nodding. Yeah. OK. OK, OK, OK. So Ivan, I know this is like a really rough drawing, but what do you think this like where I drew this little blue guy with all the stripes inside? What do you think I organelle? I was trying to illustrate by that. Yeah, I'm not really sure. But I'm going to guess mitochondria maybe. Yes, OK, you interpreted my drawing correctly. And then Brianna, the the green and the orange are like little round organelles that like degrade things. Are those lysosomes? Yeah, one of them is lysosomes is very good. And then the other critical organelle is like the cilia, which is the is this the outer? The outer of the receptors actually are modified cilium. You know, normally cilia like our move around and like help things like swim along or move along in the body. But the I think just maybe how they evolved, they were cilia. And then the other thing that degrades things is proxosomes. So we have cilia, lysosomes, proxosomes and mitochondria. So the lysosomal conditions are called lysosomal storage disorders. And then the proxosome disorders are called proxosome biogenesis disorders. OK, excellent. Oh, forgive my mess ups in my animation. So these are the ciliopathies are sometimes called like retinol blank disorders, because they frequently affect like what other organ of the body? Anyone? Your canal, your canal. Say that again. I'm guessing an inner ear canal, like the cilia in the inner ear. I don't know. Oh, they do. You know, some of them do affect hearing. Yeah, that's true. They also affect the kidneys. I'm not sure where I like, are there cilias in the kidneys? But anyway, if anyone knows, they'll free to shout it out. So and they cause like kidney cysts or nephronotysis, which is kind of like, you know how there's like eye tices with the eye shrinks and turns white. It's just where the kidneys shrink and. OK, so and get scarred. I guess Nana is not able to. It's not that well. Is that like when you I can hear you, but then when you talk, I can't really like understand what you're saying. So weird. Sorry. It's OK. It's all good. OK. So can you guys name some ciliopathies that affect that cause like a retinitis pigmentosa kind of phenotype? I asked them, so you left a clue here of a brain picture where the brain stem looks like a molar tooth. Oh, I see. Thankfully, OK. Oh, OK, Nana's coming. Saving the day with his mnemonics, so jabs. Jubeir, Alstra, Bartet, Vidal and Senior Loken. Very good. Excellent. Thanks, Nana. So. All right. So I put just three of those on here thinking that maybe these are like the most high yield ones for you to memorize, like Usher syndrome, like George said, there's cilia in the inner ear, so that causes like hearing loss and retinitis pigmentosa. It doesn't usually affect like other parts of the body. And then jubeir syndrome, that's where you look at this brain stem and it looks like a molar tooth. They also tend to sometimes have ocular colobomas. And then the classic thing with Bartet Vidal is an obese kid with polydactyly. So these are the ones that really like stuck out in my mind as like maybe the most easy to remember, flash most testable. Nana's sharing more. Oh, Usher syndrome and ciliopathy have been classified separately in the BCSE. So they're saying that Usher is not a ciliopathy. Yeah, I'm not sure why. OK, OK, well. Thank you. Thank you for keeping us straight, Nana. Appreciate that. OK, so lysosomal storage disorder. So as we mentioned, lysosomes degrade things. So when you don't degrade things, things build up inside the cells and then they start all that trash building up inside the cells, make this kind of toxic. So what are some lysosomal storage disorders that cause like a retinitis pigmentosa type of issue? OK, Nana says, Fabry, question mark. So Fabry is a lysosomal storage disorder that does affect the retina. But interestingly, some of the lysosomal storage disorders cause like a retinitis pigmentosa type of phenotype. And then others cause like a cherry red spot and, you know, vascular tortuosity. I'm sure some researcher could explain to you why or someone with a deeper biochemical understanding could explain to you why. But so the ones that cause a retinitis pigmentosa like phenotype are the neuronal seroid lipofutinoses. It's also called baton disease and also the mucopolar saccharidoses. So Hunter, Hurler, Shea and San Filippo. So all these cause like retinitis pigmentosa. So I think hopefully Brianna, do you know what the inheritance of Hunter disease is? Hunter syndrome? I definitely used to, but I don't. I can't recall now. It's OK, Ivan. Excellent. OK, yeah. So excellent because I have this like mnemonic where like it's like the hunter drawing the bow or something. So what do you think the rest of these are? Brianna, what inheritance do you think they are? If you're going for a pattern, are they all excellent? They're mostly autosomal recessive. So the one that like stands out, they tend to like pick the ones that like stand out to be on tests. So like whatever is different, they tend to like test that more. And the way it might come up on a test might be kind of tricky. Like they might say, oh, this got like passed down through the family, the patients like, you know, only passes. It's only passed on through the woman in the family and only men get it. You know, so that might be like a way that it might show up on the test. So the rest are autosomal recessive because they tend to be like severe enough, especially like Shea and Hurler and neuronal steroid lipophusinosis that like people might die before they can reproduce or at least be severely disabled by that time in their life. So and the obviously the things that are building up are the oh, I have a typo here, but the muco polysaccharidosis, glycosamino glycans are building up those large carbohydrate sugars and then the steroid. Something or another like lipofusion, I guess, is like, you know, a build up of, you know, lipid crash. So that is what's building up in bad disease. So what are some I think we talked about like the neurodegeneration and death that can occur with these diseases? What are some other like ocular things that can come up with the muco polysaccharidosis? Anybody? OK, corneal haze, very good. And so the front of the eye can be affected by corneal haze as well as glaucoma, especially in hurler or shea. How about like in the back of the eye? It doesn't cause cataracts. I haven't heard of it causing nice diagnosis, I guess it would depend how early in life it started. But it causes optic atrophy. Or edema, so that's the key thing to remember. And then how about the rest of the body for the muco polysaccharidosis? Don't try to talk, Nana. It's not working. Maybe get closer to your mic when you're done eating. OK. OK. So the key things like about like hunter, hurler, shea, sanfilippo is that those like carbohydrates, those like glycosaminoglycans large, negatively charged long chains of carbohydrates are like building up in the face. So they cause coarse species. And then they also build up like in the liver and the spleen cause a petal splenomegaly. OK, excellent. You guys have been really great about participating. Thank you. And they can also just cause like developmental delay. So it might not necessarily be on the on the milder spectrum. You know, they can just be developmentally delayed and have like a normal lifespan and not get progressively worse and die. So OK. So then there's proxosomes. And they tend to be problems with the proxosomes forming. That's what biogenesis means. And the proxosomes degrade lipids, although the lysosomes degrade lipids and many other things, proxosomes are like specific to degrading lipids. Anyone name any proxosome biogenesis disorders? OK, very good, very good. So Zellweger and Neonatal Adrenal Lucidistrophy, Refsum, thanks, Nana, for filling that out. So there's kind of like they're not all referred to that as a Zellweger spectrum disorders, that there's just a recognition that these are caused by mutations in the same gene and that there's just like a range of how they present. And there's generally speaking, either develop a delay or neurodegeneration death and increased fatty acids in the blood because the body is not degrading it. And there's also like adult refsum disease, which is not a severe. And what's the one characteristic finding of that? It's ichthyosis. So like a scaly dry skin. So, Chase, do you have a guess for like what's the inheritance of the Zellweger spectrum disorders? I feel like I don't know. Well, I mean, if they're all grouped together, I feel like the Adrenal Lucidistrophy was x-linked. They're actually they're actually autosomal recessive. OK. Yeah. Because, yeah. Anyway, that's the best. Whenever you're not sure, go with the autosomal recessive for these like things that are really bad. But yeah, all right. So next we're going on. Thank you for being willing to put a guess out there, Chase. Really appreciate everyone is willing to participate. So the mitochondrial disorders are next. So what do mitochondria do? They provide energy or ATP. So along with that, there are some systemic findings. Anyone have any guess like if you don't have enough ATP, what might happen or for your eye kind of what might happen? So ATP provides energy without it, like your muscles really don't work too well. So you might have weakness. They also have hearing loss. I think that maybe the years take a lot of energy, just like the retina does. And then classic on pathology is like ragged red fibers. And then with the eyes, like the key muscles are the ones that lift the eyelids and the ones that move the eyes around. So they get chronic progressive external apothalmal plegia, which is where like you get progressive ptosis, like the eyelids are grouping and then they can't like move their eyes to the side. So those are the characteristic things. Anyone other than Nana, no any names for these? OK, well, so there's curnsayer. I think that's like the most like well-known of these. What's like a really important thing to know about like with curnsayer in terms of like their survivability? They're like cardiac abnormality. Like they don't get block. Yes, they get heart block. Very good. And then the other two are like kind of easy to remember because like they have like their their name basically describes what's happening. So there's mitochondrial encephalopathy. So the brain's like not working to all and then lactic acidosis because the muscles are not getting ATP. So they're requiring lactic acid to work and then stroke and then maternally inherited diabetes and darkness. OK, you guys are doing great. Really, the the retinal degenerations are like the biggest block of them and you have survived thus far. So thank you. So this kiddo ended up having Zellweiger spectrum disorder. It's kind of was difficult to tell the parents that, you know, she probably will be like severely disabled. And depending on where she falls in that spectrum, she may progressively like lose her her functioning and potentially even like die in her teens or her 20s. So Emily Spoth, our genetic counselor, felt that like with her presenting late, you know, not being diagnosed late until late. That, you know, that was like a good prognostic factor, but also like, you know, her did not had genetic testing due to like family not following up. And maybe she could have been diagnosed like a few years earlier, at least. OK, does she have the characteristic face? Yeah, she her I'm not sure what the characteristic face is for Zellweiger spectrum disorders, but it definitely wasn't typical. Hypertealer. Oh, yeah, she had hypertealerism. You know so much, Nana. You're really impressing me. OK, my students, once you get it, once you get to this point in in a residency, you'll know as much as Nana. I'm looking forward to that. OK, all right. So in a large forehead, yeah, yeah, I'd say that. OK, so we did retinal degenerations. The other phenotypes, fundus hypopigmentation, cherry red spot, and that's the tortuosity and myopia retinal detachment excellence. We're making good progress. So this is a five month old who got just brought to the ophthalmology clinic because he wasn't tracking, I don't know why, but we weren't able to export the photos that day. So you can see me and Glen hovering over in the reflection of the screen, taking a picture here. Chase, do you know what this finding is called? Where this part is like kind of white around the fovea and then the middle is darker. Going off of what the categorization was, maybe cherry red spot. Yeah, cherry red spot. Yeah, very good. Excellent. So this area looks kind of like red because the area around it is all whites and you can't see the coroid below. Like normally you can see the coroid through the retina. So and the coroid's kind of reddish. We've got a lot of blood in it. What other conditions can cause a cherry red spot other than the inherited disorders affecting the retina and the rest of the body? The area. George. Oh, yes. Yes, Brianna, a way to go. Yes. So a retinal artery occlusion. So with the retinal artery occlusion, like because the retinal arteries supply the inner part of the retina, whereas the coroid supplies the outer part of the retina. When you have like ischemia of the retinal arteries, then the inner retina tends to be like what swells and turns white. And then you get this cherry red spot appearance too, because in the fovea, there's not that much inner retina. So you can see the foveal pit pretty well. Okay, excellent. So and then what can we tell already about this child's prognosis prior to like getting any additional testing? This patient's doctor, Dr. Jardine was already trying to mentally like prepare the parents for what the diagnosis might be. So we can already tell that they're probably going to fall into that neurodegeneration and early death category. So all right. Well, Dr. Jardine had that conversation, not me. So some gross generalizations again, recessive is definitely the way to go for most of these, most likely, and then the neurological problems. So as we talked about when Nana brought up Fabry disease before, is that these are also lysosomal storage disorders, but instead of having a buildup of like osominal glycans or steroids, it's a buildup of sphingolipids. So they're the sphingolipidosis and then there's also the trinucleotide repeat disorders. So I think in med school, you learn about these things. I've since forgotten a lot, but there's like cerebral sides, ganglion side, sphingomyelin, but I think they basically are a lot involved in the brain. So that's why you really get that neurodegeneration. And so what are the diseases that cause cherry red spots? Neem and pick. Neem and pick. Tasex. Tasex. Tasex, good. One more. Can Gauche, oh wait, no. Yep, yep. Okay. Gauche's disease? Gauche's disease, or I don't know how to pronounce it, but so yes, very good, excellent job. You guys are impressing me. So Gauche also causes like these peripheral white spots and the brain is really not too bad. And then what was the one disease that caused the retinal vessel tortuosity? That's a lysosomal storage disorder that Nana brought up previously. It's Fabri disease. And what else does Fabri disease cause other than retinal vessel tortuosity? There's a problem with vessels elsewhere in the body. Are there kidney issues? I'm not sure if they have kidney issues. Someone Google it and let me know. But they get this angio-keratoma corporis diffusum. So potentially like on O-caps, or on boards, they might like show you a picture of the skin with you like red elevated lesions. And also corneal overtressalata is a classic finding. What other like inherited disorders cause like elevated skin things? And I think like what general category? Angio-phycomatosis or? Yeah, they are the phycomatosis. So the phycomatosis are another thing that like you should spend a lot of time memorizing. They often affect the skin as well as the eyes and show up on tests like quite frequently cause it's the kind of thing where, oh, like if I see a ERM in like a 12 year old, like this could be kind of blanking. What is it called? I'm totally blanking. Oh my goodness. What is it? Congel hammer toe, one of the red on RP. But what is the disorder, the phycomatosis that it goes along with? There's a type one and a type two. Okay. Yes, neurofibromatosis. Thank you. I was having a brain block. Thank you, thank you. So they're, you know, these are like frequently tested things. So, all right, excellent. And then Fabry is one of those that's excellent. So basically most of these disorders that we've been over so far all are all recessive, except for like which one do we discuss that was excellent? Hunter. Yeah, Hunter. And yeah, I think that was the only one. So Hunter and Fabry, remember those. Or there's different inheritance. Okay. And then there's a trinucleotide repeat disorders. What is like an example of a trinucleotide repeat disorder that doesn't affect the eyes that like we all learn about in med school? Huntington. Huntington, very good. Excellent, yeah. So what is the inheritance of Huntington's and other trinucleotide repeat disorders? Doesn't it like more likely to affect you a younger age, depending on like if your dad gave it to you or something like that, like it's your father. If your parent, yeah, if your parent gave it to you, like do you need two parents to have Huntington's nor to have Huntington's? No. Okay, so that makes it autosomal. Autosomal or recessive or dominant. Autosomal dominant, yeah. So yeah, so just having like one parent past that, you know, CAG repeat on to you is enough to like have it. So that's autosomal dominant disorder. And then the ones that affect the eyes, so I guess I only put one on here. I'm excited to cut back. There's only one on here. And it's a myotonic dystrophy and it causes some like classic eye findings like this pattern dystrophy and a Christmas tree cataract. And then it also causes chronic progressive external aphthalmoplegia. Do you guys remember where chronic progressive external aphthalmoplegia came up previously in this lecture? In Ceres. Yeah, Ceres. Yeah, and what kind of, and then what kind of retina problem did Ceres have? Like which class was that? Which category? Which we don't type. It was a life. It was just like three minutes. Mitochondria. No, it's mitochondria, thank you. Yeah, it's a mitochondrial. And then what are the eyes, what do the retinas look like in Ceres? So they look like retinitis pigmentosa. Cause like basically everything that we went over prior to now was like a retinitis pigmentosa, retinal degeneration type of thing, rod, colon problem. So current Ceres had that plus the chronic progressive external aphthalmoplegia. The other thing that myotonic dystrophy shares with, that is heart block. And when these people try to like, with myotonic dystrophy try to grab onto something they have trouble like letting go. So that's like really like characteristic thing of this disorder. Okay, got you guys are doing really great. So this kiddo got diagnosed with Tay-Sachs disease and eventually like, cause when you're five months old, like it's hard to tell someone's developmentally delay, but eventually you got diagnosed with global development of delay and then he started having seizures. And then the family decided to go with hospice and like avoid any life prolonging measures, but they're trying to do whatever they can to make his quality of life good. So that right now is just taking seizure medications. Okay, so we went through retinal degenerations and cherry red spot slash muscle tortuosity. And next we just have fundus hypopigmentation and myopia plus RD. So this is a 10 year old male with a history of nystagmus. His best corrected vision is 2100. I would love to have like a better case of this disease. So if any of you guys like come across one where the fundus photos weren't taken in like 2005 in black and white, I would really appreciate that. So please let me know. And I guess George, what's abnormal on this, on this fundus autofluorescence here? I would say maybe it's missing like the typical like pigmentation that you'd expect. Yeah, normally in the fovea, there's like this black spot because of the macular pigment blocking the lipofusion in the RPE from it's like absorbs it so it doesn't get captured by the camera. So this person is like missing the normal type of autofluorescence of the fovea. And then when you do an OCT, you can see that they have no fovea as well. So, and you can kind of see when you look at this like photo of their eye that their eyes are very blue, their eyelashes are very white. And you can kind of see it like a red reflex through their iris, which is called iris translumination. Anyone want to say what they think this is? Ocular albinism. Yes, this is albinism. There is like ocular which like only affects the eye, not the skin and hair and then ocular cutaneous albinism. I'm thinking that based on this hair color and skin color that this might be like a ocular cutaneous albinism. Okay, now to inheritance. So ocular and ocular cutaneous albinism have like different inheritance. So this is another case. Well, I guess what the two inheritances are. What are the two options? What the two things have come up mostly so far? Auto-cell and recessive and X-linked. Yeah, auto-cell and recessive and X-linked. I need to look at the next page to see which one is which. Okay, let's go to the next page. Okay, well, let's go back. Well, we'll go back to that. Okay, what are other causes of like fundus hypopigmentation? There's algeal and then wardenberg. So those are just things to like keep in mind. Every ophthalmology resident gets very familiar with algeal syndrome because they get like a million inpatient consults because like some kid is having what kind of problem and then they want you to look for what kind of problem in the eyes. Is it posterior embryotoxin? Yeah, posterior embryotoxin. So what is posterior embryotoxin? Like a thickened decimation, I think? Maybe one of you could not explain it better but there's like this white line near the limbus and I think it's, yeah, some issue with the corneal endothelium but I think isn't some layer like growing more anteriorly on the corneal than normal? I don't know. Waiting for Nana to explain it. But, okay. And then, okay, it does represent an anterior protrude, a posterior protrusion of decimates. Okay, all right. So Nana and George are on the same page there. So, and then anyone remember anything about Wardenburg? So they have like a white forelock and they have like iris heterochromia. So they're two irises are different colors. Okay. Now we're gonna, and Horner's? No. No. Okay. I was trying to talk but, okay. They both have heterochromia. Oh, alligial and Wardenburg? Okay. Waldenburg? No. Okay. I don't know. Whatever. Oh. Okay. In general, Horner's and Wardenburg both cause iris heterochromia. Ah, yes. Okay. Okay. No, I don't know where you're coming from. Okay. Thank you. No, thank you very much. Okay. I really appreciate that. Okay. And then, so since I don't remember which diseases inherited which way, we'll click on the fill in the blanks here. So the ocular albinism is X-linked and then the ocular cutaneous is also more recessive. And then there are other variants on albinism that like are frequently tested because they affect other parts of the body, Chediakigashi and Hermanski Poodlock. So those are definitely worth memorizing. So what are the key eye findings of albinism in general? We talked about iris heterochromia, foveal hypoplasia. Our patient had nice stagmus. A lot of times these, because they're foveas are not well developed, they don't fixate that wall, so they have nice stagmus. Anything else? Okay. Oh, and oh, the visual growth potential is asymmetric because they have like abnormal wiring of their optic nerves. So a decreased visual acuity, usually the visual acuity is not normal. And then systemic findings of albinism. What are the key two things that like occur systemically that are most prominent in Chediakigashi and Hermanski Poodlock? So like if you saw someone with albinism and you want to think about like, oh, do we need to worry about these other conditions? Should we get genetic testing for them? Lots of infection, you know? Yeah, infection and bleeding. So both these disorders are characterized by those. And the P in Poodlock should help you remember that Hermanski Poodlock also has platelets, pulmonary fibrosis and it's more common in Puerto Rico, but it can also occur in other countries. Oh, yes, okay, very good. Oh, a blonde fundus. That's something I didn't even put on there because I was like so obvious to me that I forgot to say. So when you, what we mean by a blonde fundus is like people that are like very like light skins, their retinal pigment epithelium also tends to be really like lightly pigmented. So you can see their choroidal blood vessels really well. So like if we go back to this picture, it's like, wow, we can really see like every single blood vessel in their choroid versus this is like more of a normal fundus, not, I don't know, normal, but more typical fundus pigmentation where it's kind of hard to see the choroidal blood vessels. I have to say, I did a med school in New Jersey and I didn't like do any away rotations elsewhere. And when I first came to Utah and I was intern, I like asked Trent Richards, my senior resident, I was like, what is wrong with this person's eye? Cause their eye, inside their eye looked like this. And he was like, you looked and looked, he was like, he couldn't figure out like what was abnormal about the person's redness. But then eventually we just realized it never like seen the inside of a blonde person's eye before. So since I did med school in New Jersey. So anyway, if you are like just really lightly pigmented, like a lot of Utahns are, this can be normal. And sometimes the question comes up like, is this normal or is this like albinism? And that's where we just involve our experts like Erica works, I'm not an expert on that. Okay, let's, we'll keep going here. Okay, so retinal detachments in adult. Oh, yeah, we're on our last category. We're almost at the end. The end is in sight. Amazing. We do one more lecture though. But I don't know, maybe we should skip it. Okay, biopia and retinal attachments. So this kid with thick glasses and retinal attachments. So this is like what retinal attachments often look like in adults. This is actually an adult retinal attachment. But I thought I would show you a picture of like a retinal attachment in a kid. She's a teenager. She's had really thick glasses since she was age four. So four is like a really atypical age for needing thick glasses. And she, they figured out she needed glasses cause she was like holding things really close when she was in preschool. And she's never been quite 2020, but her optometrist said, like, you know what? I can't get your vision to be any better than 2070 in the right eye and 2125 in the left eye. So this right eye on this picture, on these like big circles, these are actually like macro cysts in the retina. I'll show you my drawing of it. So basically she had like an inferior retinal detachment and she had these like big macro cysts. So when you have a retinal detachment for a long time, the retina just starts like falling apart from itself and then it makes these macro cysts. She also had like a hole in a attach retina. You can see up here. But basically she'd had like some little holes right over here and then the fluid had like trickled down following Linkov's roles and just like kind of filled up her eye from the bottom to the top. And then her vision just went down and then she's got a little sub retinal fluid on her OCT scan. I just sigh because I did not do well. It was 2070 before I operated and now it's like hand motions with hypotiny oil in the front of the eye, band carotopathy anyway. So this left eye did better. It used to be her worst eye but now it's her better eye. She had a chronic detachment and you can see these like weird pigmentary changes here. Those are like demarcation lines. So when the retinal detachment is there for a while, the retinal at their edge, the retinal pigment epithelium tends to like make some changes that can be hypo or hyperpigmentation, hyperpigmented. And then eventually the retinal detachment might progress, pass it and make like a new line. But in this case, the retinal detachment had like progressed all the way to like here. So all the way past those. And then she's got some like fibrotic bands, sub retinal bands here. And then you can see that her maculose detached on the OCT shallowly. So when the detachments are shallow, you know, they can be compatible with like pretty reasonable vision, you know, like 20, 70. So that's just the example of like a chronic detachment like in a kid. So they don't all look like that. But definitely the things that made me think, okay, there could be some syndrome going on was the fact that she'd had glasses since she was age four and she has these detachments. So I thought I would show you this video. I better share a different screen. So can you see my YouTube? Yes. So you can see here, there's like this membrane in the vitreous. And this is one thing that they, you can see in stickler syndrome is that the stickler vitreous, I would say, it's not as like black and white as people make it out to be in terms of like optically empty, but in general, it's abnormal. So it can have this membranous appearance. It can look like the vitreous of a 80 year old where instead of being like really like uniformly like scattering the light, it can have like denser fibers and then less dense areas. Let me go back to sharing my other screen. So her vitreous actually had that membranous appearance in both eyes. So then I was thinking, okay, likely to have what disease? Stickler. Yep, stickler syndrome, very good, excellent. So with the myopia and retinal detachment disorders, they're gonna be an exception to our general rules for the inheritance for these disorders. Generally speaking, these conditions that cause myopia and retinal detachment are problems with extracellular matrix proteins, structural proteins, for which having half the amount is not enough. It's not like an enzyme, like a lysosomal enzyme that causes, you know, a lysosomal storage disorder where having half of an enzyme is enough to do the job. You know, if you don't have enough bricks to build your house, you're gonna have, if you have half the amount of bricks, it's not gonna work. So what are, other than stickler syndrome, what are some other diseases that cause myopia and retinal detachment? Okay, Wagner syndrome, good. Okay, so I did, I skipped what I did there. And no block, just in the name of like, let's get the most highly tested ones on here, but those are other diseases that cause like these same phenotypes. And what are the genes that cause stickler syndrome? There are the collagen genes. So like call to A1. I don't, and call 11A1. I guess that's as far as I would go with like, the memorizing of the genes that cause stickler syndrome. Don't get too crazy. And then, so I also put Marfan syndrome and while Marchesani on here, because these can cause myopia and retinal detachment as well. So, but I would say that probably in Marfan syndrome, like the retinal detachment is not as prevalent as stickler or as young. So, but if you see, yeah. Okay, and what gene is mutated in Marfan syndrome? The FBN1 gene. Yes, very good. So FBN1, and that encodes fibrillin. Fibrillin, oh, so the collagen are major, are what make up the vitreous of the eye and then the fibrillin make up what part of the eye? That's kind of like a ligament that holds the lens in place. That when it's broken, the zonules, yes. So the fibrillin makes up the zonules. That's why when you have Marfans, you might get ectopia lentis. So, we have ectopia lentis. We talked about stickler. Oh, and the other systemic findings for stickler are PR robot, meaning like, well, I think this is something that the residents also get really familiar with, even though they've tried to shunt all the NICU consults to the peds attendings. I think you still see them. So what is PR robot? So PR robot is like when the face is not developing properly. I forget what's like the, it's like a constellation of things that all come together when things are not developing well in the lower face together. So you get like a small jaw and then the tongue sticks out. So that's like glossoptosis maxillar hypoplasia. No, that's the cheeks. But then the mid-face is kind of flat because the cheeks don't develop that well either. And then you get like cleft lip and cleft palate. So many times like when there's babies in the NICU that have like all those problems with their lower face, they might have like problems breathing, problems feeding because of that small jaw that then they might console ophthalmology and ask us to retinoscope them to see if they have like the congenital myopia. But I wonder if these days they should just like genetically test them. I don't know, it would be more high yield than rena-stoping them because you can have stickler syndrome without early onset high myopia. And then I think you guys know about Marfan syndrome while Marchesani syndrome. So I'm not gonna go into detail about the systemic findings there. Okay, we got to the end. You did amazing.