Myopathy Junction and Dystrophinopathies

00:01 To put things into perspective where are we at this point? We are at the myopathies, look here we are.

00:07 So we've come out of the anterior horn, the motor. We've walked through the peripheral neuropathies, we walked through the numerous conjunction disease and now we're looking at myopathies.

00:16 Skeletal muscle disorders, myopathy.

00:19 Myopathy is nonspecific, what does it mean? It just means disease of the skeletal muscle.

00:24 You be very, very specific about the definition here please, versus dystrophy.

00:29 We're getting into muscular dystrophy, what does that mean to you? Hereditary. Under hereditary we’ll then walk into obviously Duchenne, and we’ll also look at Becker muscular dystrophy.

00:40 And I will, tell you though it doesn’t always have to be or have to be associated with the dystrophin gene.

00:46 It could be, and that’s where our focus shall be but to be technical it doesn’t have to be but hereditary is important.

00:54 Myositis, what does that mean? It means that the muscle is undergoing inflammatory process. Allow the name to speak to you, itis.

01:02 Skeletal muscle disorders, we've walked through muscular dystrophy, channelopathies are important for us.

01:09 Mitochondrial myopathy for the MELAS if you haven’t, it’s okay. I’ll walk you through it.

01:14 Distal myopathies, inflammatory myopathies, and finally we end by looking at our endocrine drug and toxic myopathies just a few words there.

01:22 Let’s begin.

01:24 Under muscular dystrophy we’ll take a look at dystrophinopathies.

01:29 Under dystrophinopathies we have Duchenne, DMD, muscular dystrophy. We’ll talk about that in great detail.

01:35 Becker muscular dystrophy, we’ll talk about that in great detail.

01:39 These are dystrophies, what does that mean to you? Hereditary.

01:43 Limb-Girdle muscular dystrophy has taken on quite a bit of prominence, so therefore I must discuss it.

01:49 And finally myotonic dystrophy as rare as it may be, once again, it appears, trust me, only words in the boards so good stuff to come, let’s go.

02:01 Under dystrophinopathies, how do we begin in general? Proximal weakness including neck flexors.

02:07 Usually will spare the ocular and bulbar.

02:11 Pseudohypertrophy of the calves, what the heck does that even mean? It means that you're going to develop or accumulate look and think about where you are, your lovely calves, okay.

02:23 It looks big. Oh, that’s sexy! But what's going on? It’s not muscle, its pseudo hypertrophy.

02:29 What the heck is filling it up? Fibral fat, okay, fiber fatty changes.

02:34 Pseudohypertrophy, it’s a lot worse than we think. I'm being a little silly there but seriously, this is no joke for the patient.

02:42 Gower’s sign. With this dystrophinopathies especially Duchenne, we have a patient that is not even able to get up by himself and so therefore they have to then do the what? Climb up their legs, they have to climb up their legs or with using their arms, it's called Gower’s sign.

03:01 And relentlessly progressive, so we have to talk about that dystrophin gene won't we, because it is the anchor for your skeletal muscle.

03:10 Associated cardiomyopathy, that is a huge point. At some point in time if you lose your dystrophin, not only are you going to lose the ability to conduct yourself in your skeletal muscle but the heart muscle is also going to be affected. So you'll have cardiomyopathy, no doubt.

03:26 And unfortunately, respiratory insufficiency may lead to ultimately the death to your patient, but cardiomyopathy is right up there, isn't it? Under dystrophinopathies, so both DMD or the Duchenne and Becker muscular dystrophy are due to different mutations of the dystrophin gene, that’s the only thing that they have in common, is that clear? The only thing that they have in common is that it’s a defect in the dystrophin gene, it’s on the X chromosome. X-linked recessive.

04:01 Labs, marked elevated creatinine kinase as you can imagine because the muscles are involved and can be diagnosed with genetic testing to forego the muscle biopsy, that’s important.

04:13 If you're suspecting, high suspicion of your dystrophinopathy, either Duchenne or Becker, then you can forego the muscle biopsy which is always nice but genetically it will tell you what's going on X-linked recessive but then, please understand, Duchenne will be more or less your frame shift type of mutation that you talked about in genetics so there's absolutely no dystrophin, there's absolutely no dystrophin so therefore with Duchenne your patient’s going to present extremely young, by the time your patient is 15, 18, 20, he is already, why it’s say he? Take a look at the inheritance pattern. X-linked recessive, right? The male has one X, and if that X is deceased boom, the man has it or the young adult has it, and by the time he is 18 or 20, wheelchair bound.

05:10 Treatment, management is going to be supportive only. And if you take a look at the Mendelian type of inheritance in the schematic you'll notice here that X-linked recessive we have the male is going to be affected quite a bit.

05:24 In order for the female obviously, both excess have to be affected and then you can be a trait obviously in a female.