From the NIH National Center for Biotechnology Information site, about halfway down the page, under "Mapping":
In a family with acetazolamide-responsive atypical myotonia congenita, Ptacek et al. (1992) found linkage to SCN4A; maximum lod score = 3.56 to 4.19 at theta = 0.0, depending on assumed penetrance varying from 0.7 to 1.0.
The abstract for the Ptacek, et al., study, "Linkage of Atypical Myotonia Congenita to a Sodium Channel Locus," is here.
Thursday, January 27, 2011
Tuesday, January 25, 2011
Part of Conversation with Dr. January at First Appointment
Me (kind of tearily): Ever since I got the genetic testing back, I've been so worried that I've given my son, this active, hiking-all-the-time kid, some crappy disease.
Him (kindly, but very firmly): Hold it right there. You didn't give him anything. If he's smart and good looking, you didn't give him that, and you didn't give him this. It's the luck of the draw. If you have some kind of original sin or guilt, you need to take those issues somewhere else to deal with.
It was exactly what I needed to hear, and my husband and I burst out laughing.
Him (kindly, but very firmly): Hold it right there. You didn't give him anything. If he's smart and good looking, you didn't give him that, and you didn't give him this. It's the luck of the draw. If you have some kind of original sin or guilt, you need to take those issues somewhere else to deal with.
It was exactly what I needed to hear, and my husband and I burst out laughing.
Monday, January 24, 2011
A Suspect! Myotonia Congenita, We Have a Few Questions for You.
The appointment today was wonderful. Dr. January at the University of Pennsylvania took me very seriously and believes he knows what the problem is. The physical exam he gave was the most thorough I've ever had, as was the medical history he took.
He's ordered a few blood tests, which he expects to be negative (and, in fact, I've had them more than once before and they have always been negative). He also ordered an EMG that he will perform (remember, this is at a premier EMG lab), and I'll have that in a couple of weeks.
The suspected culprit is myotonia congenita. [Edit: I had this wrong when I first wrote up this entry; I thought the doctor was talking about paramyotonia congenita, mostly because the gene almost always associated with myotonia congenita is CLCN1; SCN4A is associated with paramyotonia congenita. However, I just got a copy of the report today; right there in black and white, Dr. January says he suspects "myotonia congenita." I did a little digging and found a couple of studies saying atypical cases of myotonia congenita can be caused by mutations in SCN4A.]
I was very active as a child, teen, and young adult, but Dr. January didn't seem to be surprised or bothered by this. (I do recall the sensation of muscle tightness even as a child, but it didn't slow me down, and I didn't know it might be abnormal.)
The doctor also said that the symptoms of myotonia congenita can be managed, and that there are better drugs available to treat the muscle tightness than any I have tried.
The news that this disease can be managed is the best news of all. It was a tremendous relief to hear that even if my son is at risk for this disease, his quality of life will not necessarily be compromised even if he develops it.
I'll let you know the results of the EMG in a couple of weeks; I'm expecting to see something (after all, I've already had one abnormal EMG), but I'm not sure what. I also don't know if the kind of activity seen will make a difference diagnostically.
He's ordered a few blood tests, which he expects to be negative (and, in fact, I've had them more than once before and they have always been negative). He also ordered an EMG that he will perform (remember, this is at a premier EMG lab), and I'll have that in a couple of weeks.
The suspected culprit is myotonia congenita. [Edit: I had this wrong when I first wrote up this entry; I thought the doctor was talking about paramyotonia congenita, mostly because the gene almost always associated with myotonia congenita is CLCN1; SCN4A is associated with paramyotonia congenita. However, I just got a copy of the report today; right there in black and white, Dr. January says he suspects "myotonia congenita." I did a little digging and found a couple of studies saying atypical cases of myotonia congenita can be caused by mutations in SCN4A.]
I was very active as a child, teen, and young adult, but Dr. January didn't seem to be surprised or bothered by this. (I do recall the sensation of muscle tightness even as a child, but it didn't slow me down, and I didn't know it might be abnormal.)
The doctor also said that the symptoms of myotonia congenita can be managed, and that there are better drugs available to treat the muscle tightness than any I have tried.
The news that this disease can be managed is the best news of all. It was a tremendous relief to hear that even if my son is at risk for this disease, his quality of life will not necessarily be compromised even if he develops it.
I'll let you know the results of the EMG in a couple of weeks; I'm expecting to see something (after all, I've already had one abnormal EMG), but I'm not sure what. I also don't know if the kind of activity seen will make a difference diagnostically.
Saturday, January 22, 2011
Specialists' Specialists
My neurologist looked at the results of my genetic testing and suggested I see a specialist he really respects. I'll call her Doctor Very Busy. Unfortunately, according to Doctor Very Busy's receptionist, I could only get on the waiting list for an appointment.
My general practitioner was doing his own research at the same time, at came up with two names. The first name was that of a specialist who could see me in June. I'll call him Doctor June for now, but I'll change his name in a bit. The second name was that of Doctor Very Busy. Turns out I wasn't even on the waiting list to see Doctor Very Busy - because there is no waiting list. Doctor Very Busy has decided to limit her practice to ALS patients. So my general practitioner asked to whom Doctor Very Busy recommended patients she couldn't see go, and was given a name. My amazing general practitioner got me a February appointment with the recommended doctor, so I'll call that doctor Doctor February.
Earlier this week, I got a phone call from Doctor June's receptionist. Doctor June had an opening; could I come in on Monday? Yay! Doctor June is now Doctor January. And Doctor January heads one of the most prestigious neuromuscular research centers in the country.
I'm quite excited; I really do think I am getting close to a real answer now. (Remember, CFS is a syndrome, so it doesn't explain anything causative - an underlying disorder, such as a genetic disorder, can cause the physical symptoms that get labeled CFS.) I'm also a bit nervous. "Important" doesn't begin to describe the significance of at least one of these upcoming appointments.
My general practitioner was doing his own research at the same time, at came up with two names. The first name was that of a specialist who could see me in June. I'll call him Doctor June for now, but I'll change his name in a bit. The second name was that of Doctor Very Busy. Turns out I wasn't even on the waiting list to see Doctor Very Busy - because there is no waiting list. Doctor Very Busy has decided to limit her practice to ALS patients. So my general practitioner asked to whom Doctor Very Busy recommended patients she couldn't see go, and was given a name. My amazing general practitioner got me a February appointment with the recommended doctor, so I'll call that doctor Doctor February.
Earlier this week, I got a phone call from Doctor June's receptionist. Doctor June had an opening; could I come in on Monday? Yay! Doctor June is now Doctor January. And Doctor January heads one of the most prestigious neuromuscular research centers in the country.
I'm quite excited; I really do think I am getting close to a real answer now. (Remember, CFS is a syndrome, so it doesn't explain anything causative - an underlying disorder, such as a genetic disorder, can cause the physical symptoms that get labeled CFS.) I'm also a bit nervous. "Important" doesn't begin to describe the significance of at least one of these upcoming appointments.
Wednesday, November 3, 2010
Test Result Details, Etc.
Sequence variant in the SCN4A gene at transition A > G, nucleotide position IVS19+10.
From the report: "Since this type of sequence variant is similar to those observed in disease-associated mutations and benign polymorphisms, the nature of the variation prohibits definitive interpretation."
Forty other variants in the SCN4A gene have been linked to a variety of muscular disorders. Also, disease-associated mutations of the gene have a high penetrance, which means that carriers of the mutations have a high likelihood of developing the associated diseases.
But again, the report basically says that there isn't enough known about the variant I have to determine whether it is associated with disease or not.
Soooo . . . 40 other variants in this gene are known to cause muscle disease, I'm sitting here with the same darn symptoms, and the lab can't say, "Yes, this is a problem"?
However, the lab does say that "careful reconciliation of this molecular data with this individual's clinical and family history is highly recommended. Athena strongly recommends genetic counseling for this individual and his or her family members, and consideration of testing for family members."
SCN4A gene variants can be both inherited and sporadic. Inherited forms are autosomal dominant, which means a child who has just one parent with the defective gene has a 50% chance of having it as well. My symptoms go back many years; I may have had mild symptoms even before I had my son.
For more information about the gene itself and the kinds of problems its mutations can cause, check out the SCN4A page at the National Institutes of Health US National Library of Medicine.
From the report: "Since this type of sequence variant is similar to those observed in disease-associated mutations and benign polymorphisms, the nature of the variation prohibits definitive interpretation."
Forty other variants in the SCN4A gene have been linked to a variety of muscular disorders. Also, disease-associated mutations of the gene have a high penetrance, which means that carriers of the mutations have a high likelihood of developing the associated diseases.
But again, the report basically says that there isn't enough known about the variant I have to determine whether it is associated with disease or not.
Soooo . . . 40 other variants in this gene are known to cause muscle disease, I'm sitting here with the same darn symptoms, and the lab can't say, "Yes, this is a problem"?
However, the lab does say that "careful reconciliation of this molecular data with this individual's clinical and family history is highly recommended. Athena strongly recommends genetic counseling for this individual and his or her family members, and consideration of testing for family members."
SCN4A gene variants can be both inherited and sporadic. Inherited forms are autosomal dominant, which means a child who has just one parent with the defective gene has a 50% chance of having it as well. My symptoms go back many years; I may have had mild symptoms even before I had my son.
For more information about the gene itself and the kinds of problems its mutations can cause, check out the SCN4A page at the National Institutes of Health US National Library of Medicine.
Monday, November 1, 2010
Test Oddity
I called today to get the results of the Athena Complete Myotonia Workup that the last neurologist ordered. (He originally ordered it instead of the VGKC antibodies test, but then added the VGKC to the order.)
All of the standard components that indicate myotonia were normal. However (boy, it feels good to have a "however" - it feels good to have anything resembling a clue at this point), there was one component of the test that was strange. One of my sodium channel results was odd. Evidently, there is an aberration in my DNA sequencing relating to this one sodium channel.
The neurologist who left me the message with my results (who is filling in right now for the one who ordered the tests) said that the channel in question was not known to cause problems and was not commonly tested [update 11/04/10: clearly, I misunderstood this bit; the gene, SCN4A, is sequenced because it has many variants that are known to cause problems; this variant is one whose significance is unknown], and that the clinical significance of this result is unknown. But that sounds a whole lot better to me than "clinically insignificant," which seems to be the go-to phrase for test result hiccups.
I do have to wonder why this component was even part of the test if this sodium channel is not known to cause problems and no one knows what aberrant results might mean. In other words, why test for something that means nothing? Surely it must mean something to someone.
I missed the neurologist's call by about five minutes, so I called back immediately and left a message asking him to call me back. Hasn't happened yet, so I'll post when I know more.
All of the standard components that indicate myotonia were normal. However (boy, it feels good to have a "however" - it feels good to have anything resembling a clue at this point), there was one component of the test that was strange. One of my sodium channel results was odd. Evidently, there is an aberration in my DNA sequencing relating to this one sodium channel.
The neurologist who left me the message with my results (who is filling in right now for the one who ordered the tests) said that the channel in question was not known to cause problems and was not commonly tested [update 11/04/10: clearly, I misunderstood this bit; the gene, SCN4A, is sequenced because it has many variants that are known to cause problems; this variant is one whose significance is unknown], and that the clinical significance of this result is unknown. But that sounds a whole lot better to me than "clinically insignificant," which seems to be the go-to phrase for test result hiccups.
I do have to wonder why this component was even part of the test if this sodium channel is not known to cause problems and no one knows what aberrant results might mean. In other words, why test for something that means nothing? Surely it must mean something to someone.
I missed the neurologist's call by about five minutes, so I called back immediately and left a message asking him to call me back. Hasn't happened yet, so I'll post when I know more.
Friday, October 8, 2010
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