Hello, I stumbled upon this board as part of my recent research. I've been down an unbelievably long and frustrating health journey as I imagine many of you have, which has left me unable to work at a young age still without clear answers or treatments.

Just last week I got a genetic test back that indicated I have a mutation on my SCN4A Val781Ile, which is associated with ayptical myotnia, and myotonia congenita, myanthesia congenita, but the lab said it was uncertain it was causing my symptoms.

The problem is my disabling symptoms are:
severe visin problems (double vision, blurry vision, light sensitivity)
cognitive problems / headaches

I do have some other more classic symptoms like periodic weakness which is sometimes severe, and pain, which I see echoed on this board a lot, but my top symptoms are not a clear-cut match.

Does anyone else have this experience of having atypical myotonia symptoms, or just lots of extra symptoms that aren't known in the literature? If this mutation really was causing my symptoms it would be pretty much the biggest breakthrough in my life.

And unfortunately I was the one who insisted I get this genetic test, so I'm in the same boat as many of you where I realize no one knows anything about this, to the point where they can help me figure out if this mutation is causing my symptoms.

Thanks for an input! Oh I should just reinforce I do NOT have what I would call muscle rigidity, I do have weakness, and lots of pain. That's why I really am not sure what to make of this.

Type of Myotonia: Ayptical myotonia or paramyotonia

That's a tough mutation to correlate with symptoms. At least one researcher felt that it was benign. Dr. Lehmann-Horn who is a prominant sodium channel researcher lists it as non-pathogenic in his article on Hyperkalemic Periodic Paralysis Type I.
HyperKPP Type I
It is possible that it is a benign mutation as far as causing periodic paralysis or myotonia, and your symptoms are caused by another condition.

What you describe sounds very much like myasthenia gravis. Have you been tested for that? The literature used to say it was painless, but newer studies are contradicting that:

Pain Often Overlooked in Myasthenia Gravis Patients

As you mentioned, there is a congenital form associated with SCN4A mutations. Yours is not specifically mentioned, but since it is a possibility, I would ask for testing.
Congenital Myasthenic Syndrome

This is what Gene Reviews says about the pattern of inheritance:

"This condition is most commonly inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

"Rarely, this condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family."


Let me know what you think -

Jan

Type of Myotonia: Thomsen's

Country: US

Wow, it seems like I've come to the right spot. Thanks Jan for your expertise. It's amazing that you know more about this than my doctor. Your help is much appreciated!

I found that study indicating that particular SCN4A mutation is likely benign, but then I found some newer studies indicating it may not be:
http://www.ncbi.nlm.nih.gov/pubmed/18046642
http://europepmc.org/abstract/MED/15583983

Regarding congenital myasthenic syndrome, it fits in a way because it can cause for example double vision but i have severe vision problems beyond just double vision, neuropathies, and so on, really more resembling MS on paper than anything else (from testing I have ruled out MS).

But even myasthenic syndrome is a fatigueable weakness, and that isn't too apparent with me. I suppose it is in my eyes, but when I have bouts of weakness they are totally intractible and unresponsive to anything. Those bouts of weakness sometimes make it hard to shave, eat, etc. And a couple of times I got to the point where I couldn't move my arms or legs at all, but that is rare.

I read Joe's post as well indicating it is possible it is causing sensory neuropathies but there just isn't enough research on it yet. That would be sad if that's the case because I'm so sick of fighting an uphill battle having to deal with something that no one knows about and to convince my doctors how disabled I am from my symptoms.

So my hunch is that it is a major causal factor if not the major causal factor in my symptoms. Part of that is because I have so exhaustively ruled out other pathologies that it makes this a lot more likely.

But the question is how to prove that it is, and then deciding whether it is an ayptical manifestation of mc, pmc, or congenital myasthenic syndrome, or if it is a different clinical entity that hasn't been researched enough yet.

Thanks for your informative response, and I will try to get in touch with you as well Joe!

Type of Myotonia: Ayptical myotonia or paramyotonia

Hi, lou
I am also disabled by way of an SCN4a "benign" snp. I was forced to diagnose myself after Neurologists accused me of lying about my symptoms.
I got the requisition from Athena Diagnostics over the internet and filled it out myself. My GP who openly professed no knowledge of neurology signed it (I am sure just to humor me).

There are ancillary conditions that are associated with some sodium channel gene defects. The severity of the ancillary condition is NOT related to the severity myotonic muscle disease.

There are so few people affected that it is suggested (with a question mark)that sensory neuropathy is connected to some sodium channel defects.
A long standing sensory neuropathy often affects the eyes.

Email Jan and have her give you my email address. I can share many documents that my research has found, and give you some suggestions on testing.
Thanks, Joe

Type of Myotonia: SCN4a

Country: US

Hi, lou
I checked the LOVD (Leiden Open Variation Database).
The SCN4a (xxDNA change)p.Val781Ile defect has been reported once
as producing hypokalemic periodic paralysis.

The database lists a number of DNA changes that produce the same amino acid change.
Thanks, Joe

chromium.liacs.nl/LOVD2/variants.php?select_db=SCN4A&action=view_all&order=Variant%2FDNA%2CASC&hide_col=&show_col=&limit=250

That string deliberately does not produce a link but if you copy it into your address bar with or without "http://" as appropriate it should take you to
the right place.

Type of Myotonia: SCN4a

Country: US