all right um well thank you to MDF for having me and thank you all for joining here in person or online um let's get started I will be talking about my tonic distrophy type one or dm1 I will be talking about genetics about symptoms and a little bit about how to manage symptoms so first of all how many people live with myotonic DHE type 1 or dm1 um previously sorry oh okay uh previously we were um we thought that it's about one in 8,000 people in the US that have myotonic destrophy but a recent study um we learned that it's actually a lot more people that have myotonic distrophy and about one in 2,100 people carry the genetic mutation that causes tm1 that is about 140,000 just in the US and um that means that there are people with tm1 in the community that are not diagnosed underrecognized that may or may not have symptoms and do not know why they're having symptoms and what we'll be talking about is what symptoms do people with dm1 experience why does dm1 cause so many different symptoms and how can those symptoms be managed so let's get started with with what symptoms do people experience and I just want to start with a disclosure because myotonic distopy type one is extremely variable in fact it's one of the most variable diseases in medicine and that means that people can develop their first symptom anytime throughout a lifetime some people develop their first symptom at Birth some people in the first decade second decade third decade fourth decade and some people develop their first symptom at older age in their seventh decade so that's a huge variability in disease onset and severity in addition myotonic dropy is also very variable in terms of what type of symptoms people develop most conspicuously the muscle is involved um you see on the left hand side muscle weakness and myotonia for example and we'll talk about that um but in variable ways people may have other multisystemic symptoms such as involving the GI system cognition sleepiness some people have diabetes others do not um some people have weakness of the breathing muscles eye involvement with cataracts and that can vary so just bear in mind as we go through these slides that some of these symptoms May apply to you and some may not because the disease is so variable so now let's move to why does ton cause so many different symptoms and why does it infect so many different organ systems it's called muscular distrophy but it's not just a muscle disease in fact it can affect all types of tissue and to answer that question why that is we have to make it a little bit more complicated and go into the genetics and so the following slides will be a little harder um but we'll get through it and I do want to go through them because when we are in an exciting time in myotonic distopy as you heard from multiple people because we're about to um or at least we believe that we have therapeutic strategies to treat metonic destrophy and not just the symptoms but the really the root cause of the disease at the genetic level and that's why it's important to understand a little bit more about the genetics and about the mechanism of the disease because as more treatment trials are coming your way um it's important to understand where does it Target where at what level is the root cause of the disease being addressed and so let's start here with the genetics again it's a genetic disease and here you see the chromosomes that everyone inherits every one of us and we have 22 pairs one chromosome is inherited by Mom one chromosome is inherited by dad and myotonic destrophy is located on chromosome 19 and the gene is called dmpk Gene and that sits on chromosome 19 and you may see here that dm1 is right there the cause of dm1 and the type two myotonic destrophy which shares a lot of features of myotonic distrophy and there's a lot of commonalities um it is actually on a different gene on a different chromosome so there are distinct genetically distinct diseases they just share a lot of mechanistic and symptomatic uh features but just that to to understand that they're separate um so how is tuman inherited it's what we call autosomal dominant that means that as you can see here um there is an affected parent and that affected parent has one one copy of the of the myotonic DHE Gene that is abnormal and one copy of the myotonic DHE Gene that is normal now the the child um of that person has a 5050 chance of inheriting the abnormal copy of the mitony gene so this individual here in in green that is a affected by myotonic distopy has a 5050 chance of inheriting a myotonic distopy to a child and that is like flipping a coin and independ it it is independent of how many family members already have miton gy so for example if a couple has three children and two of them have myotonic ghy and one does not based on genetic testing if they have a fourth pregnancy a fourth child the chance is again 50/50 flipping a coin and that's what we call AAL dominant so now let's um zoom in a little bit on the chromosome on the miton jopy gene in called dmpk here in blue and take a huge magnifying class and focus in on the DNA the DNA is made out of building blocks that we call nucleotides and they come in a repetitive order so here you see ctg ctg ctg that's a repetitive code that we all carry nearby the DMP K Gene everyone has that code but what's different between people with and without myotonic distopy is that people without myotonic distopy usually have up to 37 of those repeats of those 30 of those ctg ctg repeats now in myotonic distrophy you have more than in blood cells on the DNA in blood cells people have more than 50 repeats of that those ctg ctg repeats and I just spoke about how variable myON dm1 is clinically it's also very variable genetically so people can have in their blood cells more than 50 that's diagnostic of myotonic dropy but people have a range of repeats so the repeat length can vary from 50 to over a thousand and why is this a problem if you have too many of those repeats on your DNA um at the DNA level we'll have to move on to the RNA level and just as a reminder the DNA is is kind of the template the code that gives rise to all the proteins that were made of and so the DNA gets transcribed into RNA which you see down in the blue box and the problem is that this extra repeat is transcribed into extra too much RNA repeats and they are just then cug C cug and so there's too many of them and so now you may ask now still I don't know what's the problem if you have too much DNA on there well um if we zoom in really closely on muscle tissue which you see on the left hand side here um and we take a close look and do extra staining what we can see is that that extra RNA those extra cug cug cug repeats they actually don't just float around in the cell in the nucleus no they stick together because there's so many of them they kind of build these clumps we call them toxic clumps um and they Clump together and when you stain for them they pop up like this you see that little red spot that's the c u expanded repeat now why is it Troublesome to have these clumps because the clumps itself don't cause problems yet but when we move on here there are important RNA binding proteins important proteins that float around in the nuclei of ourselves and those important proteins have really important jobs to do but and I will comment on what they do in a second but the issue is in dm1 is that these important RNA binding proteins they get stuck in those clumps they get trapped in those clumps and because they're trapped in there they can't function properly anymore and so what does these RNA binding proteins look like usually well in a healthy cell they would just float around in the nucleus and be available to do their job but in ionic gy or dm1 you see down there that they're stuck in the nucleus and they lose function now what do they usually do oh you give me one second so to prove here visually that they actually are stuck exactly in those clums when you merge those images so staining for the repeats staining for the important proteins the repeats are in red the proteins are in green and when you merge those pictures here's the proof um the the the clumps actually really trap those green proteins now what do these proteins usually do um why is it a problem that they not do not function properly anymore well they usually edit and splice rnas from numerous other genes so there are other genes that have nothing to do with myotonic DHE Gene but they are dependent on those RNA binding proteins to edit them and make them pretty and cut them so that they properly can be used is a template to form proteins that make up our body and so to give you an example what that actually means there is for example a chloride Channel RNA from a chloride Channel Gene and that RNA needs those proteins to be edited it's not happening properly and that's why myotonia occurs then there's a calcium channel RNA it's not properly edited anymore because the proteins are stuck there and so weakness occurs and then there is an insulin receptor RNA that's not properly spliced and edited anymore because the proteins aren't available they're stuck that causes diabetes similarly a sodium Channel RNA um isn't properly spliced anymore that causes irregular heartbeat and so on and so on um that is the cause why myotonic distopy causes so many different problems not just in the muscle but in other organ systems um I mentioned earlier that dm1 can cause symptoms at any age from birth to the sixth decade um and so we are interested to understand why does dm1 affect people in so different ways and specifically even within one family and to um by as a disclosure we don't have the answers but we have some ideas and I would like to introduce two concepts of why that is and the concepts are called anticipation and somatic instability and both uh both uh relate to the problem that this expanded repeat the ctg repeat is just incredibly unstable what does that mean let me see that okay what does that mean well if the repeat the genetic mutation is inherited from a parent to a child it has a tendency to grow bigger in size and to actually not just grow bigger a little bit but to have huge jumps um so in the germ line the repeat is unstable and it has a tendency to grow and what does that result in specifically when the disease is inherited through a mom there is a chance that this jump is is particularly big and so what you see here there's grandmother who is mildly affected by myotonic justop Fe type one and then her daughter is a little bit more affected and then the child has has the congenital form of myotonic distopy and throughout those Generations from generation to generation the repeat grew in size and the disease became more severe and that's what called anticipation now the other concept is that the repeat isn't just unstable from generation to generation but that it also is unstable in certain tissues body tissues throughout a person's life so what that means is that the repeat grows in size in some body tissues throughout life and it grows in different tissues at different rates so for example all of or a lot of you may have had their blood tested for the mutation for the dm1 mutation in fact blood cells in blood cells the repeat doesn't grow a lot it's fairly stable that may not come as a surprise to you because there isn't really myotonic distrophy symptoms related to blood cells there isn't really a problem with blood cells however in the tissues depicted down here on the bottom the muscle tissue the heart and the Brain in some people there the repeats grow a lot in size throughout a lifetime and we think that that is triggering off the disease or worsening the disease throughout a lifetime now let's shift gears from that and talk about a little bit how symptoms can be managed I would like to um just um say upfront that I I learn a lot from you and I learn a lot from my patients I see in clinic and what I always hear is that it's with living with a rare disease even though I told you it's a common rare disease um finding a team of therapists and doctors familiar with the condition is hard depending on where you live in the United States it's even harder and so the alternative is to find a team of therapists or doctors that are willing to learn about it which is the most important thing in general because I still learn um and I will learn uh moving forward so it's extremely important that people are willing to learn from you and through care guidelines because there are care guidelines that MDF uh put out and um that you can alert your doctors or your team to and that also sometimes means have your doctor reach out to an expert have a phone call have them have a phone call things like that and if they're willing to do that I I think that's that's worth a lot and so with that I'll move on to some of the symptoms that you're well familiar with um but one of the symptoms that often is the first symptom in um reported by people with dm1 is the myotonia and the myotonia is the delayed relaxation of um the delayed relaxation of the muscle so making a tight Fist and then opening it it gets stuck and I have a video here here I'm not sure I really need to show it because you probably all know but I can't show it because I can't click on it so we have to skip the video but you know you know how that looks like um and I just wanted to I I um actually this video demonstrates the warm-up phenomenon which you are all familiar with in the cold weather it's it's worse in the warm weather it's better um and so the more um and the more you use your hands the less uh pronounced the munia is the delayed Rel like ation so to the point that people tell me well I would try to get into my house in the winter in the winter it was snowy outside and I couldn't turn the door knob because the hand was stuck and usually that person is able to do it but just in the cold weather um it was impossible which can be quite um difficult so how we can actually treat myotonia with medications and that these myotonia medications treat the symptom um so they relieve the symptoms and choices are maxatin and roline important is when you bring that up to your doctor that they check an EKG first because those are medications that can have an impact on the heart rhythm and so you want to make sure that it's safe for you and your particular situation to to be on those medications but for some people um and I usually ask my patients how much is myON an issue is it bothersome and if it impacts work for example I have a patient who is a nurse in an in an emergency department she has to do all these little caps and and do IVs and so that was really important that the myotonia was treated others may not feel that's a big issue in their activities so it depends on on the individual whether we treat or not and then moving on to muscle weakness so BM1 causes weakness preferentially in certain muscle groups and those are depicted here in red which are usually called distal which means it's those muscles are a little bit further away from the trunk so the hands the forearms and the lower leg and then as the disease progresses other muscle groups um nearby the the P the the hips and the shoulders can be affected too a muscle that's often early on affected also as the neck flexors so for example lying in the bed and lifting the head from the bed can be difficult um or for example in the car and then or or in the on the plane when there are turbulences that can impact the stability of the head or I have a patient who went on a boat ride and it was hard because it was Rocky and the neck you know she had trouble um stabilizing her neck so that's the neck strength um facial weakness can occur as you know that the droopy eyelets can occur and then um weakness in in facial muscles um and then importantly there can be involvement of the breathing muscles so the diaphragm and um the expiratory breathing muscles and we'll talk a little bit about that in just a second now what to do about this I think I really hope that this talk will be different in a couple years and I will be telling you different things or someone else will be telling you different things how to manage muscle weakness and what kind of treatments are available because again we are living in a time where we think that mopy will be um therapeutically tractable soon but at the moment we don't have FDA approved treatments to um change muscle strength or the trajectory um so at the moment what we encourage is don't become too sedentary physical activity exercise there are numerous papers out there demonstrating that moving is important moving exercise is safe um and keep what you have in terms of your muscle strength by being active I do recognize that's a challenge not just because you know there's weakness how do you exercise some people cannot do what they used to do what they enjoyed doing because of weakness and then there's sleepiness and apathy and things like that that interfere with the ability to be active but anything is better than nothing and um you know I usually have that conversation with all of my patients um it's important to come up with an individual strategy so talk to your therapist about what's good for you also pick an activity that you're willing to continue doing that is somewhat fun or incorporate into um a routine or regimen if you look if you watch a show regularly maybe do it while you're doing something active things like that um the other things that can um that are important to address in the clinic is avoiding Falls because if you break a bone um that's a setback and that makes you more sedentary and lose muscle strength and bulk so we don't want that so sometimes is ATI devices are necessary and I will go through some of the next slides um um indicating what that can look like so here you see a graph this graph is made out of data from over 929 people with dm1 we uh the National Registry house in Rochester collects data and has collected data over the last 20 years from people with um with dm1 and through annual surveys so every year there's a survey sent out and we ask people are you using ankle brace have you started using an ankle brace are you using a wheelchair um we ask about Milestones of of uh disease progression basically and um all of all of these people fill it out and or a lot of these people fill it out and send it back and we're extremely thankful because that gives us an opportunity to learn from you how the how you experience the disease and when people actually need those assistant devices or use those assistant devices so so just there's a lot of data a lot of effort in just that one graph um on the X on the x axis you see h on the y- axis you see the probability of using a certain device so zero on the bottom means no one is using an ankle brace one on the top means everyone is using an ankle brace and so as you can see as people get older the risk of needing an ankle brace increases you also see that the solid line and that's what I'm highlighting here is dm1 and you see that not everyone is using an angle brace throughout their lifetime but some people are and so at age 50 for example it's about 15% that need use an ankle brace and the risk um to use an ankle brace up at age 60 is about 25% similarly when we look at Walker use um utilizing that data um we see again that's the same graph same you know y AIS is the probability um the risk of needing a walker on the x-axis is the age so at age 50 the risk of needing a walker is about um again 15% and at age 60 it goes up to about 35% of needing a walker now um the last graph um in that fashion is wheelchair use here so for example the the risk of needing a wheelchair for people with DM up to age 60 is about 20% and that's what we learn from from the registry and that helps us when I have a new patient in the clinic um I I understand that the answer the the disease is very variable it's extremely variable isn't always satisfying um and we're a little bit stuck with that but this kind of data helps us give a a ballpark of what the risks can look like um so now let's shift gears and talk about other symptoms heart disease as I mentioned you would think that muscle disease heart muscle muscle the heart has muscle it's probably the muscle no it actually isn't most most commonly dm1 affects not the muscle but the electrical wiring in the heart and that means the nerve goes to the heart and then travels um through electrical wiring through the heart and then activates the heart muscle and so that electrical wiring that transmit the signal um for the heart is impacted and so what can happen is that there's slowed transmission or even the transmission is totally stopped and so that is called different or varying degrees of heart block what kind of symptoms do you have when you have heart block um you may have no symptoms you can be what we call asymptomatic um people can have symptoms such as dizziness um or when there's irregular heart rhythm heart chest pain palpitations things like that but again it can be associated with no symptoms or sometimes people have trouble when they sleep and so there are no symptoms when when you sleep um what is necessary is to have an EKG every year um no matter how old everyone should have an EKG every year and I have had um the experience that people told me yes I went to see a primary care physician or even a cardiologist and they told me my EKG is fine and they said I don't have to come back and that's not true so you have to have an EKG every year because if the EKG is fine that's great but um it's possible that those conduction problems can occur later in life or throughout a lifetime so it's important to keep monitoring that and it's recommended that if you have symptoms if the EKG is abnormal or when you're on the older side um greater than 40 um to consult a cardiologist in general a bottom line the threshold to see a cardiologist should be low so an ultrasound of the Heart is also recommended but less frequent so usually not every year unless it's indicated and your cardiologist once recommends it um the treatment for these heart issues the heart block is Pacemaker and in rare instance this is a defibrillators indicated the pacemaker kind of picks up that work and then Paces your heart um if there is a problem um with uh with the transmission of the electrical signal and in the registry what we learned is that um as people age the risk of needing a pacemaker increases and that's about 25% uh for people up to age 60 and then increases after that so it's important to so again as you can see not everyone needs a pacemaker but um a decent fraction of people do and so it's important to keep monitoring now I will transition to something that's incredibly important um particularly in my experience in younger folks excessive daytime sleepiness um excessive daytime sleepiness means not just being tired but either having a huge sleep requirement you know sleeping hours and hours more than everyone else or not feeling rested in the morning or take having to take naps uh during the day or um falling as sleep in situations where other people may not fall asleep and that does not refer to you know after lunch having had a big meal no it's more you know in situations where it's really um excessive and I know from from from people that this and in some studies too um that this can be quite impactful on people's lives I do appreciate and recognize that is specifically in younger folks in their 20s who are trying to have a job have a career go to school or even in teenager years um and then had to stop had to stop their their their their wishes and dreams because of excessive daytime sleepiness and sometimes it occurs that at the time they didn't even have a diagnosis of myotonic DHE and so you know um it was it must be even more struggling if there is no real cause for that and no explanation but excessive daytime sleepiness when I talk about that in clinic I usually try to highlight three possible causes in the setting of The one and one problem that can contribute to excessive daytime sleepness is sleep apnea sleep apnea Central or obstructive now let me say a couple words about that because sleep apnea is well familiar in the community right A lot of people have sleep apnea in the community and usually you know risk factors for sleep apnea in the community is if you if they're overweight short neck things like that but that's different in myotonic distopy um if you have weakness of these muscles here in the neck and they relax in everyone when we sleep and those weak muscles relax even a little more um in patients with dm1 then sometimes it's hard for the air to go out and and be expelled um so that can cause obstruction obstructive sleep apnea now Central sleep apnea refers to when the Sleep Center in the brain is not regulating the breathing properly and that happens in dm1 as well because dm1 can have effects on the brain and specifically the Sleep Centers so sleep apnea is uh important to think about when someone has excessive daytime sleepiness the other possible contributor is weak breathing muscles and I'll just comment on that a little bit so um the weak breathing muscles the breathing muscle is the diaphragm and when we breathe in the diaphragm moves down when we breathe out the diaphragm moves up so when we sit gravity helps us because it pulls down the diaphragm now when we lie down flat in the bed the diaphragm doesn't help doesn't have help of the gravity anymore and has to work harder to go down and up for in breathing in and breathing out so often times when people have weakness of the diaphragm because that is a muscle um it can cause problems first at night when asleep because the diaphragm just gets tired of doing all this work um and so that can cause headaches in the morning or being really groggy in the morning or shortness of breath when lying flat um when these other muscles here are involved also it can be Troublesome to cough or you know clear sputum um if people have frequent respiratory infections it's also important to look for that and I'll talk about how to how to assess the breathing muscles in just a second but weak breathing muscles if you don't breathe well at night if the diaphragm has to work hard and is not breathing off the CO2 um sufficiently at night it causes you still sleep but the sleep is not as restorative and so people can be tired during the day um and then the last cause of contributor to excessive daytime sleepiness related to dm1 is just the effects of dm1 on the brain and sleep and the sleep centers so there are people who have no sleep apnea and totally strong breathing muscles but they are still sleepy during the day and that is because there is just um the the dmpk gene is also causing these expanded repeats and the expanded RNA and those toxic clumps they do occur in the brain as well not in everyone but again in some people and so that by itself um can cause the sleepiness so some people have a combination of one cause both all three um it varies but it's important in clinic to tease those out and how do we tease those out well we recommend spirometry so where you take a little device um and you breathe in real strong um and you breathe out and then it measures how much air fits into your lungs and how strong your muscles are um in in breathing in and breathing out and we do that sitting and lying down and most people that I see in clinic haven't had it lying down down and I just explained why we do that the lying down test because lying down we take away gravity and if there's a little bit of weakness of the diaphragm we can pick it up when someone is doing the test lying down because again gravity doesn't help and so that's what we recommend for the sleep apnea um and this the issues with breathing overnight we recommend the sleep study um preferably inpatient your doctors May order a pulse oximeter little little thing that you clip on your finger when you're at home at night that is good for sleep apnea and the general population out there but it's not as good for people with myotonic Dy because dm1 sleep issues are more complex and so an inpatient study is really uh important now why are we doing these things and why is it important to tease those out well because there is a treatment for the Sleep uh for the sleep apnea and there's a treatment for the weak breathing muscles and that involves non-invasive ventilation so wearing a mask at night that helps your diaphragm um breathe breathe in and breathe out now I do recognize it's hard to tolerate that sometimes and I hear from my patients that have tried and tried and it's hard to tolerate and some um are unable to tolerate it one thing I would like to mention though because I've heard so many different stories um sometimes it's worthwhile to keep trying for a little while try different masks make sure you have a provider who is willing to go that road down with you and not just say oh you didn't tolerate done okay you didn't tolerate it so there's not nothing we can do it's good if you have someone on your side who who keeps working on this because I have had patients who've tried for a little while and they actually were able to find a regimen settings a device there are numerous devices out there um and there's new ones coming on the market all the time that we're able to find the right match and make it work for them and that's important it may or may not make you feel better during the day but treating it is important because it can have other impacts on um Health um um in general if you don't breathe well overnight and if you have untreated sleep apnea so it's important to pay attention to that now if you still if you have nonivasive ventilation and you still feel tired during the day or you actually don't have sleep apnea and you don't have weak breathing muscles but you're sleepy then medications can help if they are safe in your situation and those are stimulants now how many people actually use those non-invasive ventilation the mask at night when we look at the registry data it was about 20% of people with dm1 using devices up to age 50 um we are not asking who had it prescribed and wasn't able to tolerate so that's actually the people able to use it now let's shift to GI symptoms there is an extra talk on this um and I I um would recommend um attending those GI talks because um there aren't a lot of people out there in the community that are um or GI Physicians that are really familiar with with uh dm1 it's it's it can be difficult um G GI symptoms can affect any the GI tract anywhere from the mouth swallowing all the way down to the spincter um symptoms can impact can involve difficulty swallowing abdominal pain constipation bloating diarrhea either or both or alternating there is um people with dm1 have gall stones and oftentimes have their gallbladder removed earlier than other people um in you know general population um and so I do recognize GI symptoms can be incredibly um disabling you can go outside with hand weakness but some of my patients cannot go outside if they have a bad day of GI symptoms um that that can be really impactful on on on lives and we recognize that um the good part is that GI symptoms have are due to impact affected smooth muscle so so the muscle in our Limbs and in our breathing muscles that's um SK muscle and mangopy also causes problems with smooth muscle and the smooth muscle is again in the GI tract in some other organs like the female organs as well and so um again I hope that this part of the talk will be different in a couple years we don't know for sure but hopefully um these the smooth muscle will also be therapeutically tractable um when we have therapies a Target getting the root cause of the disease now um how to monitor for these GI symptoms again it can be frustrating but consult a GI specialist and again have a GI specialist that's willing to learn with you and go along that road um with you even though they might not be familiar with myotonic distopy at the beginning um myotonic distopy Foundation has put out care guidelines and there's a long list of things in the care guidelines also listed down here some of them what to try and my experience is people always need to do trial and arrow because one regimen may not work for another person and the other way around and some people have develop have found even supplements and certain um you know over-the-counter things that help them and then also identify try to identify food triggers um that may you make you feel worse so again recognizing um they have a lot of impact they're they can be difficult to treat um and the therapies that are listed down there they're all non-specific so we don't have a dm1 gii treatment these treatments that are out there are really used for anyone who has these kind of GI symptoms for whatever cause a word on anesthesia surgery just make sure your doctors know about it there is um MDF has the anesthesia guidelines online that have been around for a long time and it's just one sheet so the the short version so just take that sheet with you give it to your anesthesiologist and make sure they're willing to look at it um and bottom line is that dm1 uh people with dm1 can be more sensitive to sedating medications more sensitive to opioids for example um that can worsen uh GI symptoms of course uh constipation but they can also make people more groggy or affect the breathing and then if you're in a cold o the mitonia can get worse and then just make sure your heart is checked out um before having a a procedure generally speaking I say it's good before having a surgery it's good to have team of doctors that are willing to learn about my tonic jopy but it's also good to know your breathing status do I have weakness of my breathing muscles or not and what does my heart look like um what does my EKG look like those are the important aspects uh a word on cancer because there is an increased risk um for cancer um including melanoma and um some some OB uh cancers such as of the uterus thyroid cancer colon cancer um but I'm not here to um you know that shouldn't scare you um because the risk is of course when we look at this if we looked at the cancer risk in the general population you would see it go up with age because there is just an increased risk of cancer for for everyone but when studies were done it did show that there's a slight increase um in dm1 and the mechanism there are some hypothesis of why but we don't know exactly why yet but bottom line is that when we asked in the registry uh for example um people um 24% of people for example reported up to age 60 that they had some type of cancer diagnosis in their lives and what does it mean no you do not need scans from head to toe um what it means is you should follow with ag appropriate cancer screening so basically what should everyone should be doing I would just encourage you particularly to do which means see a dermatologist every year I do recommend that for for everyone but just see a dermatologist every year to make sure there aren't any um uh uh suspicious moles or so um and then follow up with your OBGYN and you can discuss a thyroid ultrasound with your doctor um the caveat is we don't know how to screen for thyroid cancer there is no screening for thyroid cancer um the risk of having ultrasounds of the thyroid is that something is something is found like an abnormality and then you have a host of medical appointments and tests and it may turn out to be nothing and there's all that what's associated with it um that's the risk basically um but that's something to discuss with your doctors whether you should have whether you know a thyroid ultrasound should be done and then I do recommend you know if you have it done every three years and then you're you're good um I want to end that was a lot um and again a lot of symptoms a lot of problems that can occur but I want to end on this note because I'm told you that it's a that it's not useless to go through these slides because really um I hope that uh uh and I I uh it's a disclosure that it's a hope but I do I do strongly believe that we'll have a little bit of different talks in the next couple years and that the symptom management hopefully will morph into to uh a different conversation about targeted treatments that's what we envision for the future and that's what we are all working towards too um and so what are the strategies how how do we want to tackle this not just treating symptoms but really tackling the root cause and so approaches that you will hear about are targeting the DNA itself really going into the DNA and and cutting out that that Gene or cutting out the repeats that's difficult to do and this is not coming to the clinic anytime soon because it's difficult to do and it will take a little bit more work but that's one approach the other approach that is actively being tested and that you will hear about is um tackling it at the RNA level so not making permanent changes to your DNA but really for example cleaning up those clumps out of the nuclei um and releasing those proteins by cleaning out those those uh clumps and so that's what's being done right now and being tested um in in the research centers in people now the last approach would be for example to not just clean out the clumps but just releasing those proteins that are trapped in the clumps because if we release the proteins then they can float around and add it and supplies all these rnas again and hopefully reverse symptoms or improve or stabilize symptoms and so releasing those proteins from the clumps is another approach that you may hear about in the future and with that I want to um U close and thank you for your attention and uh take questions you call the question you pick up oh yeah I was wondering if they know why um it's usually worse quote unquote worse when it's passed through the maternal line rather than the paternal line um yeah so that's a great question so question is why is it wor why why is the jump in the repeats right why is the growth of the repeat worse when it's from Mom to a child uh rather than from a father to a child so that's intergenerational jump why is it bigger um there are certain theories about that we don't know definitively but there might be um some relationship to how the gene is methylated in that area um or how the repeat is stabilized in that area but it's not not definitive um I would also I I one thing I just noted I didn't mention um the G the the sex of the child doesn't matters so it's the maternal transmission but it doesn't it which which has a risk of you know having that congenital form um of myotonic distopy but it doesn't matter whether the child is a boy or a girl does that make sense yeah okay oh maybe this side yeah yeah I have a few questions um they're basically yes or no questions um now is the muscle weakness is it wasting or just weakness um it can be both and so what happens is that there's weakness um often well let's let me take a step back so um for because it can affect people throughout a Lifetime right so in in the adult onset so beyond age 10 usually um there's weakness and then it can result in muscle wasting as well muscle wasting just means you know the muscle shrinks um and gets smaller and what we don't know though um and and that happens in some people more than others what we don't know though is that reversible or not that we will learn in the future can it be that muscle that is uh that is shrunk and wasted can that recover theoretically I would say yes but we will learn that in myotonic distopy and also um now I can't bend my fingers anymore is that that arthritis or is that part of myotonic distrophy so I can't tell if you have arthritis that's always in general you know anyone with with dm1 can have other medical problems s too right so sometimes I learn that um some do or some people doctors uh I have to you know pay attention to not do that either just chalk up everything to my tusy no it's important to really think about someone holistically and make sure other medical problems are being addressed and not everything is just you know chocked up to my Tong but the what you describe the weakness of the fingers that's very typical of myotonic G orm1 and in fact the finger flexors these muscles so when you make a fist it's hard to make the fist all together that's typical for myong and those muscles here are often affected first and early um so I would say it sounds like that's what's happening but yeah then another question um kidney function does myy have anything to do with kidney function um so good question so typic so to our knowledge the kidney isn't really uh having trouble from my iic distopy typically not but the way we measure kidney function is by measuring creatine kise so an enzyme that comes from the muscle so that can be low in myotonic distopy and so the measurement of kidney function sometimes can be more difficult in myotonic distopy because it's the measurement is is something that is related to muscle but um K if if someone comes to me and has kidney problems um I would look very broadly and not chalk it up to my tonic Dy and also I wanted to say that Aqua therapy really worked for me y so that's a good one and I also want to know about have you heard about crispy I'm sorry crispy it's yeah um so the the the hot words are always crisper which is more of a methodology um or you know method how to do how to how to um manipulate genes and um it's used widely um and then gene therapy so so gene therapy is usually um Reserve that term is usually reserved for treatments that Target directly the DNA on the DNA level like cutting out things replacing genes things like that um we don't the the current me methodologies that are being tested in clinical trials are not gene therapy but we I call them genetic therapy because they are targeting the RNA so gene therapy may be something I we do think gene therapy will be something we'll learn about in the future in myotonic distopy um but it's not not ready yet it's not entering clinical trials in the near future and near future I mean you know the next one or two years that's that's uh my perspective on it yeah excuse me yep um given that there are a number of people who walk around with this disease without knowing it it I've always wondered it's possible you could end up in a relationship with someone else with a disease neither would you neither of you would know it and I wonder what the math of of inheritance would be and I wonder whether the betting would be that the symptoms would be different than if only one parent had it and you had an affected child yes so there are reports um sorry there are reports on uh having two abnormal copies uh of that's what you're referring to right chances are low but um Can Happen and there are case reports of having two abnormal copies and to our knowledge it doesn't make a huge difference um but um what what I would say though to your point there are people walking around and they can't do Family Planning because uh because they don't know I do think that um specifically as therapies become available it's extremely important to do better ASC containment of the genetic mutation in the general population so to test more to test broadly to test more not just because then people can maybe if they want to consider that in their family planning um but also to if if therapies are available the question will be when should we treat uh if someone has is Midway through their disease course or early on or even before someone develops symptoms and that makes it extremely important to to test early yes