Yes, this is Abby questioning her diagnosis yet again. How do people with seronegative MG ever banish the specter of adult-onset congenital myasthenic syndromes?

I am the second of eight children. I know some forms of CMS are recessive. None of my siblings have symptoms...or do they? I have one sister who has been dragging herself around as long as I've known her. She's 39.

Besides testing negative for antibodies, I have little or no ocular symptoms. I also don't respond to Mestinon. I am thinking Dok-7. But, my first symptoms hit two years ago, when I was 43, which is unheard of (I read that symptoms can appear as late as age 30, but that even that is rare).

On the other hand, my overwhelming memory of childhood is being tired. I remember walking home from school every day, just dragging my feet. I looked up the distance: it was only half a mile. I spent long hours lying in bed reading.

I'm poking around on the internet, of course. I'm also taking a good look at my siblings. If one drooping eyelid in the family appears, that's going to change everything.

Abby
currently on Imuran, which my doctor is sure is going to send me into remission soon.

The honest answer is that there is no way to know. Genetic testing for CMS is still in its early days. Probably only a small part of the possible mutations are currently known and can be diagnosed.
It is also possible to have both. (genetic and autoimmune).
In fact it is probably not that rare to have antibodies directed against an abnormal protein.
I myself missed a diagnosis of a rare congenital disease when I attributed it to the antibodies I found in my patients blood. When I was on sick leave, her daughter came to consult one of my colleagues with similar symptoms. This made him brilliantly search (and find) a genetic component.

statistically it is much more likely to have sero-negative MG than adult onset CMS. Also, autoimmune MG is a potentially treatable disease in which remission is possible, whereas CMS can only be treated with symptomatic and supportive care.

Clearly, having antibodies makes those decisions much easier for both the physician and the patient.

I am relatively new to all this and in the process of getting my son diagnosed, but if you suspect DOK 7, the answer is a blood test away. They have identified the gene, and I believe you either have that mutation, or you don't. In poking around the internet, I also found a study from 2008 where they found that 2/3 of those who test seronegative are not seronegative at all...they just have low titre antibodies...in other words, the test just isn't sensitive to find the antibodies. In 2/3 of those in the study, they tested for the immunoglobulin in the endplate itself..and found it. I sit here in utter disbelief of how little is known about these diseases. At this point, they are suspecting that my son may have limb girdle CMS...the publication disclosing the identification of this gene was in February 2011. The science on this is in its infancy, and THAT is very frustrating.

Thank you Alice and sdmama.

One advantage I have is that I have seven siblings. But I did the math, and if my parents both had a recessive gene, the odds of having seven unaffected children aren't ridiculously low (about 13%).

My neurologist is so confident that the Imuran will make a big difference in as little as six months--which is this fall!--that if I don't improve, I think he will be open to doing some genetic testing.

I am not so confident in the Imuran, because I can't remember ever reading here about someone who went into remission on Imuran alone. But I'm certainly willing to try it, especially because I am worried about getting other autoimmune diseases later in life (like lupus, rheumatoid arthritis, or MS). I don't have any evidence that taking Imuran could prevent these diseases in someone who's prone to them, but it seems like a reasonable conjecture.

Abby

Abby, I think I've asked this before but have you looked at your childhood photos? Have you taken photos of yourself now? Keep the lighting, angle and distance from your face the same each time. I know you say that you don't have ptosis but are you sure? I thought ptosis was my normal growing up so I didn't notice it, not that I knew what ptosis even was until 2000.

What about asking your family members if you could take pics of them or if they could do it and forward them on to you? Ask for head shots. Do you have photoshop or any other software that could isolate the eyes and eyebrows?

I wish I could upload a pdf I have about CMS but it's too large.

Like Alice said, you can have CMS, MG or CMS and MG. They have not come close to uncovering all of the CMS's because they can be completely missed! And there are dominant CMS's with a lack of acetylcholine too, so it's possible your family has a dominant gene.

So since you're questioning things . . . are you sure it's a lack of acetylcholine and not too much of it?

Did your doctors look for a R-CMAP? It's where there's an extra muscle potential on an EMG. Some doctors might think it's feedback or not know what it is.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2924514/

I think that you should consider going to Mayo Rochester or UC Davis. They are the only ones who can tell you for sure. They will usually only see patients who have a positive SFEMG, which you do have.

Giving someone who does have a CMS Imuran would obviously be the wrong thing to do! I would want to know for sure and I did want to know for sure! I do have antibodies but that does not rule out the possibility of my having CMS and MG.

I don't have anything brilliant to say other than it's obvious that you need to know the absolute truth. Who doesn't want that? You may never get it but if you don't at least try to, I'm pretty sure it will vex you.

I hope you do figure all of this out.



Annie


http://www.congenitalmyasthenicsyndr...dromes2004.pdf

Attached Files

CMS2005.pdf (193.8 KB, 94 views)

My eyelids look the same as each other, but the distance between my pupil and my eyelid is smaller on the left eye. I noticed that months ago because I was looking for ptosis. But it seems constant--I mean since I noticed it, it's the same every time I check it, whether my eyes are feeling strained or not, or whether I'm in the middle of a weak or strong period (I am, by the way, feeling very strong these past few days! I have been doing wonderful things. I know my strength could go away tomorrow, so I am trying to remember that as long as it lasts, it's a gift.)

We had a family reunion a couple of weeks ago. All seven of my siblings came. I was checking eyelids!

I will poke around on FaceBook and through some old albums.

As far as I know, Mestinon doesn't help me or harm me. If I take too much, I get twitchy. But it doesn't seem to make me either weaker or stronger. So I have no basis for thinking either that I have too much acetylcholine or that I have too little.

I don't know...I know that the doctor who did my first two SFEMGs (and regular EMGs) was the local (= Rhode Island) expert on diagnosing neuromuscular diseases; and that the doctor in Boston that _he_ sent me to was considered even more of an expert....

I am going to give the Imuran a year, because in light of my history and my family's history of autoimmune diseases--and the fact that I came down with MG right after a big Graves' relapse--I think it's a reasonable risk. After a year, I will push for Mayo. I think that after a year's trial, my current neuro will be glad to refer me.

Thanks for the PDF! It helps my peace of mind to collect information, even if nothing medical comes of it. I feel much more in control when I'm up to speed.

Abby

The chances of that are vanishingly small. I have seven siblings. The eight of us have a total of 34 children. If there were a dominant gene, even if its expression is unusually mild, one of those children would certainly have some weird neurological problems! Even the possibility that I have a de novo dominant mutation is slim, since I have seven kids myself.

Abby

An image came to me of a few of us sitting in a room with a bunch of doctors and scientists and grilling them for hours. How fun would that be?

I think your plan sounds sensible. Might a muscle biopsy be something to do in the meantime? What's one more scar?

Heck, I don't mind. But my neurologist--this was back while they were still trying to diagnose me--said he's really reluctant to do a muscle biopsy, because they often come back confusing, and people get diagnosed with conditions they don't actually have. From what I've read since--anecdotally, mostly here--that seems to be the case.

OK, so I have been looking through FaceBook albums of my siblings for droopy eyelids, and I discovered SEVEN photos of one nephew, age one and a half, with a droopy right eyelid. The first one was so pronounced that I thought it must have just been a fluke of the camera, but then I found the others. There are also dozens in which his eyes are symmetrical. As far as I know, there are no health concerns about him--didn't have trouble eating, didn't walk late, nothing like that. He seemed like a normal toddler to me when I saw him recently. He is my brother's son. My brother has always been energetic, and he works construction.

I am just barely wise enough not to call my sister-in-law and bring up CMS (just barely), but I will certainly be paying attention.

Abby

And here's what I think Mayo might do . . . they might say that you have "familial ptosis," that it's benign and that you don't need any treatment. They like to undiagnose adults.