Congenital Muscular Dystrophy and Congenital Myopathy

00:01 So let's think more closely about congenital muscular dystrophies and congenital myopathies and really focused on understanding the similarities and differences between these two causes of neonatal hypotonia.

00:13 The congenital muscular dystrophies are muscle dystrophies.

00:17 So there is a degeneration of the muscle that's present at/around birth.

00:23 Congenital muscular dystrophies are different from the other muscular dystrophies because they begin at birth.

00:28 Duchenne's, Becker's, Limb-girdle and the other muscular dystrophies that we've learned about present much later in life, in childhood or adolescence or even in adulthood.

00:37 And that's different from congenital muscular dystrophies.

00:41 They have a genetic cause, we're going to learn that the congenital muscular dystrophies are from similar proteins involved in the dystrophin glycoprotein complex that anchors the muscle to the extracellular matrix.

00:52 There is a degenerative etiology.

00:54 The muscle is degenerating and slowly dying and necrosing over time and so these conditions follow a progressive course.

01:01 The baby begins with some strength and slowly becomes a hypotonic and weaker and weaker over time and ultimately, many patients die from congenital muscular dystrophies.

01:12 In contrast, we see that congenital myopathies are also muscle disorders that are present at/around the time of birth.

01:19 These are different from the acquired myopathies that present in adulthood and are seen at the time of birth.

01:25 There is also a genetic cause.

01:28 But here patients follow a static course or very slowly progressive course over time.

01:33 There's not degeneration of the muscle or necrosis of the muscle or dying of the muscle.

01:37 The muscle just doesn't work because of the accumulation of certain proteins or byproducts or abnormal contents.

01:45 And this results in a dysfunctional muscle that does not degenerate over time.

01:51 Let's walk through each of these, the congenital muscular dystrophies and the congenital myopathies.

01:55 And first we'll focus on congenital muscular dystrophies.

01:58 There are five that I want you to be aware of.

02:01 The first is Merosin-deficient congenital muscular dystrophy, Fukuyama disease, Muscle-eye-brain desease, Walker-Warburg and Ullrich congenital muscular dystrophy.

02:13 All of these are congenital muscular dystrophies, they present with a hypotonic infant.

02:18 Patients have a progressive weakness over time, there's degeneration of the muscle and I want you to know the five names but not be invested into all the details of each individual condition.

02:29 With the other muscular dystrophies we talked about, abnormalities in the dystrophin glycoprotein complex.

02:36 This is that protein complex that sits in the cell membrane of the muscle, the sarcolemma.

02:41 It anchors the extracellular matrix to the internal muscle.

02:45 In this docking, this infrastructure, this side of skeleton that anchors the muscle in this way is critical for normal muscle function, loss of any of the proteins that are involved in this scaffolding results in a muscular dystrophy, degeneration of the muscle and varying degrees of inflammation.

03:02 With the congenital muscular dystrophies, we see abnormalities in a number of associated proteins.

03:08 Fukutin, POMT1 and a number of different proteins that are involved in these conditions, the congenital muscular dystrophies and different from the other muscular dystrophies, like Duchenne, Becker's and limb-girdle.

03:22 Let's think about some of the features of these individual congenital muscular dystrophies.

03:26 And we'll start first with muscle-eye-brain disease.

03:29 The abnormality is with a gene in the POMGnT1, as you can see here and that's something we can test for on genetic testing.

03:38 We'll look for mutations in that gene.

03:41 The clinical presentation with muscle-eye-brain disease includes severe muscle weakness, often with mental retardation epilepsy, patients can have neuronal migration disorders and ocular abnormalities and that complex points us to muscle-eye-brain disease.

03:55 When we see patients with severe hypotonia, mental retardation, epilepsy, we'll consider genetic testing to evaluate for this condition.

04:03 What about Fukuyama disease? This is a problem with the Fukutin protein that we saw on the last slide.

04:09 Patients again present with severe proximal and axial muscle weakness, floppy baby, mental retardation, epilepsy, again, neuronal migration disorders and ocular abnormalities can be seen.

04:21 And so you can see the similarities in these two presentations and the importance of genetic testing to screen for the individual genetic event that's giving rise to the disease.

04:30 Walker-Warburg is another one of these conditions again, abnormality and a similar gene to the muscle-eye-brain disease but a different area.

04:39 We see clinical features including severe muscle weakness, death in infancy this can be quite severe, absent psychomotor development, neuronal migration disorder and abnormalities and ocular abnormalities.

04:50 And then there are several other again congenital muscular dystrophies that can present with varying degrees of muscle weakness and other conditions and genetic testing is critical for evaluating the precise diagnosis.

05:05 What about the congenital myopathies? Again, these presented infancy just like congenital muscular dystrophies.

05:11 But they are myopathy, a muscle disorder that results from dysfunction of the muscle but not degeneration over time.

05:20 And there are four conditions, names that I'd like for you to know.

05:23 Nemaline-rod myopathy, centronuclear myopathy, central core myopathy, and myofibrillar myopathy.

05:33 The key things to know about these conditions they're congenital, they begin at the time or around the time of birth, can present with a very weak hypotonic infant with difficulty with feeding and sucking and insignificant motor weakness and loss of motor or absence of motor milestones.

05:50 They are static over time.

05:52 So there is dysfunction of the muscle, the muscle doesn't work and patients are weak, but that weakness really more stable are very slowly progressive over time which is different from the congenital muscular dystrophies.

06:04 There are structural abnormalities that occur in the muscle that build up in the cell, in the muscle cell and result in inclusions.

06:12 And those inclusions are what we see on histopathology and give each of these four conditions their name.

06:18 With central core myopathy, we see a central core that's that white area that you see on the histology, and that tips us off with a muscle biopsy that we're dealing with central core myopathy.

06:28 Centronuclear myopathy, here we can see this abnormal nuclear content within the muscle.

06:33 Nemaline-rod myopathy has this protein build up within the muscle that we see on this gomori trichrome stain which is a very characteristic stain to show this problem.

06:44 And then myofibrillar myopathy, we see these fibilliar contents within the muscle.

06:48 And again, we don't need to know all the details of each of these conditions but that they're evaluated and diagnosed really histopathologically based on these findings present within a hypotonic infant with a static course over time.

07:00 And treatment for nearly all of these conditions, congenital muscular dystrophies and congenital myopathies is primarily supportive.