We will take a look at Myotonic Dystrophy.
I’d like to separate Myotonic Dystrophy
from your DMD and BMD
for the fact that it’s a completely
different type of pathogenesis.
Biochemically, we’re talking about
trinucleotide expansion disease.
Some of the common ones that you should
know include CAG mutations
and that then of course gives
you Huntington disease,
GAA trinucleotide gives you
CGG should be thinking Fragile X.
So here we have myotonic dystrophy.
This is CTG trinucleotide issues.
Now what’s going on with CTG, with the fact
that you have a mutation taking place
in which myotonin-1 is not present,
and if you don’t have myotonin,
what is or what are the
you can expect in your patient?
One other thing that I wish to bring
to your attention is that there is
something called myotonin protein kinase
known as DMPK mutation.
So some recent developments that you want
to make sure that you keep in mind,
not to worry, these are things that we
will go through as we walk through
The first thing is weakness with
sustained involuntary contraction
and refers to the myotonia.
Its atrophy of type I muscle fibers.
What are these again, please?
? Are these the endurance
or these the fast-twitch,
and hence, I went through the
review rather quickly with you.
I read slowly type I read
because it’s a slow-enduring muscle.
Is that clear?
Type II is the fast, keep that out
of the picture right now
and may be elicited by percussion. Now you
take a look at the picture here,
percussion of your thenar eminence;
therefore, then giving you sustained grip.
That’s your myotonia that
you’re referring to.
Genetics. How does auto-dominant
mutation, would be specifically
your chromosome 19 and I need
you to focus on myotonin
protein kinase called or
abbreviated as DMPK
dystrophy myotonin protein kinase.
Know that please, commit that to memory.
It’s a trinucleotide issue so therefore
what does that mean to you?
At any time that you have
a trinucleotide pathology,
you are thinking about the term
anticipation, aren’t you?
The pattern of anticipation meaning that with
every subsequent generation and progeny,
the onset of the disease gets a little
bit earlier and earlier and earlier.
Here we have CTG greater than 30,
you start worrying about your
patient having myotonic.
Signs and symptoms.
Late childhood. Gait abnormalities,
for example, weakness of the
foot with dorsiflexion;
the grip myotonia that I just showed you,
the thenar type I muscle fibers;
cataracts—take the C in CTG—cataract;
take the T in CTG
and the patient may have to wear a toupee
because your patient is balding;
and there might be issues
with the genitals—G;
CTG—if that helps you;
cardiomyopathy, and Hatchet facies—I’ll
show you a picture coming up.
In other words, what happens
with Hatchet facies
is it represents the fact that
the temporal regions
will then be exposed in myotonic dystrophy.
Make sure you know the signs and symptoms
well to make your life a little bit easier.
T—toupee, balding, and then G—genital
issues with testicular atrophy.
Do not forget about the thenar eminence
percussion causing grip and so.
Here’s a child that was born with myotonic
dystrophy, autosomal dominant.
I want you to focus upon the frontal
temporal baldness that is
already setting in in this baby.
And here’s a typical picture
of myotonic dystrophy.
The topic is ion channel myopathy.
What does this mean? Remember,
you must have an action potential
at the neuromuscular junction
so that you could have presynaptically
release your acetylcholine binding to
acetylcholine receptors which technically
is _______ sodium channel
and that sodium channel brings in or
influxes sodium bringing about then
depolarization may then result
in end plate potential.
You may then reach your threshold and
you have an action potential.
My point is, what if some of
these ions are diseased?
Well, if you can’t even properly
bring in sodium, for example,
how in the world are you supposed
to elicit an action potential?
If you can’t have an action potential,
you can’t even have a twitch.
Here we are. Ion channel myopathies.
Inherited autosomal dominant
and we’re learning more and more and
more about these ion channels.
They’re have been a couple of baseball
players, that for whatever reason,
they were complaining of fatigue and
tiredness, and the management
thought that the athletes were lazy.
Then upon further examination came to
find out that it was an ion
channel myopathy taking place.
Relapsing episodes of hypotonic paralysis
and episodes are usually
induced by vigorous exercise.
So imagine you are the baseball player and
you are trying to move from home, you know,
to first base after a bat,
and so obviously quite a
bit of exercise in that instance,
and if all of a sudden the ion
channels do not wish to participate,
and let’s say, contribute to your running,
then for the most part, you are
in a state of hypertonia.
Etiology. Well defective sodium channels
channels one possible cause. Remember you
do have other ion channels,
but the one that you want to
know for sure is one in which
the sodium channels are not working.
The patient may present with hyperkalemia,
now not only usually when you have
a sodium channel issue, you should
also be worried that the potassium
channels may be playing a role.
As far as potassium is concerned, you know
that it maintains resting membrane potential,
so therefore, if there’s an
ion __________ myopathy,
and it results in either
hypo- or hyperkalemia,
you completely skew your
resting membrane potential.
So for example, remind me again,
say that you have hyperkalemia,
and what would that do to your
resting membrane potential?
Now it would cause resting membrane
potential to depolarize,
getting closer to threshold.
But in the process ________
it also effects the sodium
channel, doesn’t it?
So now what happens is—now quickly here,
I’m just going to walk you through
some physio _____ here,
highly recommend that you take
a look the sodium channel
in great detail and physiology, where we
have the M gate and the H gate
if you remember.
So during depolarization, what then
happens with the H gate or activation gate
will close. If the sodium channel
is once and for all closed.
You will never have influx and therefore
you have muscle fatigue, won’t you?
Now keep in mind that some
of your ions or ion channels
during action potential all
need to be working in synchrony
so that you can get
proper muscle contraction.
Ion channel myopathy.
Here we have thyrotoxic myopathy.
Take a look at the patient here.
Oh my goodness, I’m about
to take my boards.
No, no, no. That is not what
this patient is doing.
What’s happening to this
patient is exophthalmos
secondary to Graves’.
So we have thyrotoxic myopathy.
So begin with proximal weakness
precede onset with signs and
symptoms of thyroid dysfunction.
So if it is Graves’ then you’re looking at
a patient who has heat intolerance,
eating food but is not gaining weight,
palpitations, and so forth,
pretibial mixed edema, exophthalmos.
This is exactly what we’re
seeing and therefore causing
exorbital hypertrophy causing
orbital movement out,
but in addition, the muscles
might be severely affected
__________ so on and so forth.
Thyrotoxic period paralysis—weakness
some myofiber necrosis
is what you’re looking for
and interstitial lymphocyte infiltration.
Interstitial lymphocyte infiltration
s what you’re referring to.
Thyrotoxic period paralysis
weakness with hypokalemia. Keep that
in mind, please. Important.
With ethanol, what it may do,
for mechanisms that are beyond pathology,
is rhabdomyolysis with muscle pain,
and eventually may leading to renal
failure as well. Ethanol myopathy.