Genetic Testing
 

I am posting the following link to a news article on yahoo. I have been involved in some work on pursuing a genetic etiology for my situation, I just want people to know that the test mentioned in this article is not it. There are far more disease specific tests. Many genetic diseases are diagnosed by genetic testing. When I first saw they were offering these genome wide tests I was excited, but after I saw they only identified some common diseases, my enthusiasm for them went down the drain. This article is quite correct, save your money...these tests are not the answer. Medical genealogy accomplishes a lot. I have done one and got some very interesting information, however it is extremely time consuming and you do need to really educate yourself. It isn't easy.

There are many hereditary neuropathies and myopathies that include peripheral neuropathy as a component. These tests will not help with identifying those. Even your ethnicity may be very vague on some of these tests, so be careful with your dollars. Website below.

http://news.yahoo.com/s/nm/20071130/...nes_testing_dc

Hi Cy

So, you might have bad genes, eh? Too bad your folks stayed on the farm for 400 years....not to mention it was one quarter of your ancestry....too bad the other 50% has some weirdo disease too...but lucky you, one test rules them all out!! It is ok that your great great granfather is also your great great uncle and your great great aunt is also your great great grandmother, and five lines of blood descend from one man....it happens. Look at the bright side.....You might find out you are your own twin!!:p

Uh, only problem, when it all does come back negative, you are back to 'idiopathic' which, even though you have biopsies indicating your axons are falling apart in a length dependent pattern and matters are getting worse....there is no way to treat it and no real cause...hmmm.:confused:

Oh my God, then to make matters worse, you are talking to YOURSELF!!!:eek:

It has to be all in your head.

OK, so this is the place to talk genes, phenotypes, haplotypes, etiology, all kinds of -opathies....and any questions as to what regions and populations may carry what genes...Population genetics, genetic epidemiology....this will get interesting.

Keep your sense of humor if you come in here---be ready to laugh at yourself---and potentially dishonor the family:D Be ready to get clinical!

Yes
 

Now we are going at it,and your it,I mean if i get the family history
out,and the genectic testing I had done in St. Louis.my son's was
was done at Mayo,and Daughters at Hopkins..And brothers in Mi.
Some had insurance pay most was research..I can go back to Great
Great Grandparents,there studies were written down by complaints,
and what they were complaining about..I think if we could keep it
in one area it would be interesting..

But I'm not first,my 91 yr old Aunt is going through many tests,and
if I don't fall on her she will be staying with us..Now on my husband's
family they went way back,but it's scary how many of his and my
family had he same medical problems...My family my Grandparents Irish,
my husband's Parents escaped from Russia...Well hush Sue, Really
I would love this,honest. Hugs to all Sue

LOL, I don't know how much of the same symptoms my family had on that one side.....but way too many of them had the same name!!

That was so funny about the names,I hope people here take a interest
in this.. Take care all Sue

My story
 

I'll bite! Firstly, let me tell you my story, abbreviated version -- I actually started out with hyperreflexia and slurred speech in my late 20's. And those symptoms, coupled with my family history and progressive neurologic problems, prompted my neurologist to send me for an MRI of the brain to capture the atrophy and he also ordered the "Complete Ataxia Evaluation" profile of tests from Athena Labs in early 2006. The profile only tested for a handful of possible types of SCAs (Spino-Cerebellar Ataxia), and to no surprise, my results came back negative for SCA1, 2,3,6, 7, 8, 10, 14, 17, DRPLA, FRDA1, and AOA1. That is why we were given the "SCA, type unknown " diagnosis -- ours is clearly autosomal dominant, that much we know, but not much more...And so here is my game plan -- I will continue with the gene testing as more tests become commercially available, under the discretion of my Ataxia specialist. Yes, I know it's a very expensive outlet for research that may or may not ever capture and reveal our faulty gene, but I'm determined to continue to pursue any type of medical research that I can, mostly for future generations. According to my specialist, ours is a rare type, possibly the next SCA yet to join the ranks of obtaining its very own number...We'll see.

Thanks for sharing your story Color. What you have been thru is truly scary and I admire your willingness to continue with the testing. What you are doing will benefit a lot of people. We need more people like you on this planet....and it would be a :grouphug:

You can see by the slow start on this thread, how difficult a topic this is for people. :eek:

I think people are confused by just the word genetics, let alone all the autosomal dominant, sex linked, autosomal recessive stuff.:confused: I still have trouble drawing a Punnit Square..I think I spelled that wrong.

I think people also are afraid of hereditary and genetic neurological diagoses, because they fear having a disease they can't treat (even tho many of the neuropathies are untreatable because we really don't know the cause.):(:mad:

Some people see genetic diseases as :o somehow disgracing the family. (In my family we do that well enough without any diseases.:D)

I think people are afraid of a lot of different things....discrimination, passing things on to their kids, telling family members if something is discovered etc. You have gone thru a lot of this testing and these issues, bravely.

This is where I hope people can come and get personal stories, information, and courage.....plus a few laughs....(I am in this thread...it is part of my genetic make-up)

Thanks for sharing your experience.:hug:

Gratitude and Acceptance
 

Dear Cyclelops,
Thanks so much for the understanding and support -- it's taken me a long, long time to even figure out that my mother's side of the family had an actual faulty gene to explain all of their problems in the first place. Yes, the concept of genetic testing is quite subjective and personal -- oddly enough however, I felt just the opposite of what you stated re: genetic diseases disgracing the family. You see, as a kid and young adult, I was always ashamed of my "crippled" relatives, basically because they were what they were, period, and that there was no explanation or personal drive to research whatsoever. The thought of it being possibly genetic never even dawned on them -- be it lack of medical knowledge in the past, concern for future generations, personal interest, money, whatever. But thanks to major medical breakthroughs in the past decade re: Ataxia (I'm referring to the disease, not just the symptom here -- FYI, and that is why the 'A' is capitalized), the sky's the limit.

And so I truly believe that things are so much more comprehensible and acceptable, from both a personal and public point of view, when you at least have an inkling as to what's going on down under... ;)

Thanks for listening! :hug:

Megan
 

I have enjoyed the posts in this thread. It's very late here and I definitely can't write anything at all humourous as I'm so tired, but briefly......

.....having one autosomal recessive condition (two mutations) and carrier status (one proven mutation) for another condition I have experienced first hand that whole family mentality of innuendo. One of these conditions is now out in the open in the family and the other one is still definitely hush, hush!

It never ceases to amaze me the lack of recognition of the fact that everyone in the human race carries about five to six mutations and even the 'perfect specimens' do as well....so why does it threaten people so much? Maybe it is just too confronting.

Which brings me to Mitochondrial mutations and genetic testing. Has anyone had mutation testing (DNA) done for Mitochondrial conditions as a cause for their neuropathy?

mitochondrial testing
 

Hi Megan,
-just a quick response (and further question) re: mitochondrial testing. I had a simple blood test for this -- to check serum lactate level. The results came back as normal, so my neuro didn't pursue his hunch any further. Is this the first step?

Thanks.

Thanks for both of your posts, it is sooo good to talk to folks who have an understanding and acceptance of the dynamics that occur with hereditary diseases.

I just had a muscle biopsy. I assume they will be looking at mitochondria. They are looking for abnormal proteins that are associated with myopathies that come with neuropathies. Some are passed thru maternal mitochondria, other myopathies are not sex linked at all, and quite a few are autosomal dominant.

I am not sure if it will be fruitful or just a dead end. All other causes for my substantial small fiber neuropathy have been exhausted at this point. If this comes back negative, then, I simply have to wait for additional pathology to manifest, or simply accept that they can find no cause.

It is wonderful that both of you undertook the journey to explore the brave new world of genetics. It will so much help the next generation, and save them so much suffering, going undiagnosed, misdiagnosed etc.

My concern is for my children. I do not want them to suffer for decades with misdiagnosis and self doubt. So if I carry a mutation, I want to know. What my grown kids do with that information is up to them. Some of it depends on what it is they find.

I do know my husband's family carries the BRCA2 gene, and just thinking about that is a bit scary. But I think a lot of people carry that gene, it is good to know it is there, and good to know that our daughters need to be vigilant.

And yes, I do think that all families carry genetic abberations and that is life.

Hla B27
 

This is an interesting thread. I myself know that I carry the HLA B27 Gene. http://en.wikipedia.org/wiki/HLA-B27 I don't have enough family left to check the link very far. I do know that my paternal grandmother, and my father also carry this gene and suffered the damage from it. My Dad has Rheumatoid Arthritis and I suspect my grandmother did too. She died when I was in my early 20's. But I remember her as being very crippled up and sickly. Her autopsy revealed she had cancer of the bone. That is three generations of defective gene. I don't know if my son carries this gene, he refuses to be tested and I didn't find out about my own in time to check his.

My defective gene is probably pretty common but the Sjogren's and it's damage isn't. That is one of the reasons that I left my DNA all over the labs at Mayo. Perhaps future generations will benefit from my history.

Billye

And, of course--
 

--there is the controversy now in gluten/celiac circles as to whether thaat conditon can manifest in those who have other than the human leukocyte antigen (HLA) DQ2 or DQ8 genetic subtype. (There's some evidence that some people who tend more towards neurological manifestations of gluten sensitivity, such as ataxia or neuropathy, are more likely to be subtype DQ1; apparently there are even a few biopsy-proven celiacs with that type, according to some of the work of Dr. Hadjivassiliou and colleagues).

I know Liza Jane has some knowledge of mitchondrial disorders--perhaps she'll chime in.

It is a very interesting area--made all the more confusing by the idea of genetic predisposition then being expressed (or not expressed) by environmental factors turning certian genes on or off. Much of what we know now will certainly go through revision and reparadigmization over the next decades.

Thanks for sharing your stories and expertise. There is so much out there. What surprised me was how many of these diseases are known, as are the patterns of inheritance. There is a lot out there we do not know, but there are many diseases, with set gene loci and patterns that we hear little about. Hearing what people do know, helps.

I did not think that much about heredity until lately. I knew it was a possibility, but just never thought that there were so many identified diseases, with known patterns of inheritance, that contained small fiber neuropathy!

It is good to have a thread where folks can share this stuff if they want to, and if they don't want to deal with it, they don't have to click on the thread.

Heh, heh...I knew I would end up here...again.:p

I just got back my muscle biopsy reports...I have some mild myopathy...not enough to account for weakness, but then again, I haven't complained of weakness there....I have been grousing about my feet, hands, neck and back.

Where was this mild but surprising myopathy??

The bicep...the old Popeye muscle. (Shoulda eaten that spinach)

They did the bicep muscle because it is the farthest away from any neurologically damaged tissue...and they found mild, but surprising, myopathy in the bicep. It is neurologically induced. Meaning, the muscle is deteriorating due to a lack of innervation, likely small fiber, highly likely hereditary, likely autosomal dominant.

They are proceeding with more study on the sample to rule out Anterior Horn Diseases, which cause the same look in the muscle cell...but are fairly confident it is a hereditary neuropathy producing a myopathy....and not just that, but it also produces changes in any organ that is not getting proper innervation, such as skin, muscle, endocrine and or exocrine glands.

Mitochondria are fine....cute little buggers....so probably that rules out any mitochondrial DNA stuff from mom...of course there are other genes from mom but....I have a hunch where this came from...but can't say right now, 'ya hey dare---you betcha-- I have a hunch'. But I could be surprised, in time.

There is no sign of inflammation. I sometimes wonder if my body is capable of getting inflammed!!! I know now, that my kids will never have to go thru the 'it's in your head' thing.

I am tossed into that black hole which will eventually spew out a lot of new constellations of diseases.:eek: Maybe in this lifetime...maybe not...but I have contributed to the advancement of science, albeit nebulous at this time. I wish I could hang my hat on a star and say, bingo, this is this specific disease, but, we are beyond idiopathic, to hereditary, we are beyond small fiber neuropathy, which it IS, but on to documenting more and more sequlae to small fiber neuropathy, and perhaps a new name for an old disease or a new disease category within a huge galaxy of what we call PN.

Beam me up Scottie!:D

Now that I have a bit more info....I want to share a few disease categories that every one should at least glance over.

Hereditary Distal Myopathies
Adult onset myopathies
Adult onset muscular dystrophies
Myotonic Dystrophy Type 1 and Type 2 (PROMM)

There are some ethnic pockets of higher incidence.

Maybe one of the folks that has been thru genetic testing would like to share their experience and definition of terms, such as dominant, recessive, sex linked, penetrance, anticipation. I get too wordy.

That said, I do want to reiterate....we are no where near finding a gene locus for me....I simply switched categories from idiopathic to hereditary, clarified it is not inflammatory...it is still the same disease, still nameless, but not faceless. This entity has faces now, and it may, possibly have lineages and names....then again it may not.

This is the third biopsy I have had: epidermal nerve fiber density shows small fiber from normal to severe loss depending on location...(the muscle biopsy done on me was very close to an area that showed normal innervation)

A muscle biopsy which shows mild myopathy, thought to be of neurogenic origin, with abnormal angular fibers...again mild.

A labial biopsy which should chronic changes without inflammation, read by Mayo as consistent with Sjogren's. 'Consistent' with is their way of saying...we can't call it that, but there is something wrong and we find this kind of thing in Sjogren's.

Again, I had NO lymphocytic infiltration, which some folks on here do have on their labial biopsies. That is important to note...as lymphocytes indicate inflammation. My gland is simply not getting innervated properly and works quite well at times. This also applies to my eyes...and it is possible that I am sleeping with my eyes slightly open due to the neurogenic myopathy condition I have....Sleeping with eyes open is called nocturnal lagopathalmos. My eyes do dry out during the night something awful....during the day they are usually OK unless something is blowing on them. I can wear contact lenses at times.

I don't know all that much about mitochondrial conditions...my experience with mitochondrial DNA is more ethnologically based...just that you can trace ancient, really ancient ancestry thru DNA passed thru mitochondria from mother to daughter. This is mostly ancestral stuff...I don't even know how much they can do for recent stuff. The original Eve stuff.....

It is disconcerting to think you have some genetic crud, and you are suffering and they don't know where it is coming from, yet...but the 'yet' is important. Everything starts with a 'yet'....from uncertainty comes certainty...which then gets blown apart by yet a new theory, which needs testing. I have kids, so I do have some real concerns....humor is the way I deal with stuff. When I was stuck in a crashed car, pinned under a truck with propane cylinders in the bay....I got to cracking jokes...(once they had my kids out....I was in no mood to be humorous when those kids were in that car and at the time, all I heard was some one say they smelled gas....I had no idea there really was GAS!!!)....there are times, there are things you just may not escape. That was one of those times....I didn't know there was propane in the back bay of that truck that hit me, and could not figure out why they needed 3 fire departments....

My humor is never, ever meant to demean any one's pain or suffering. Pain and suffering sucks...and as I said, I do my share of moping. Life can be so ironic at times, I have no choice but to see the humor in it....it is hard tho, and I hurt bad and I am scared about my loss of function and mortified at the thought I may have passed this on, and they do not know what it is yet, but we know we have lost people, early on, in my family. If they do not know what to test for, well, we can't really figure out for sure which side it is coming down on....one is very populous...the other side, there are fewer of us, and man, I do not know if they do find something, how I would ever locate them. I don't even know if people WANT this info. For me it beats having the ubiquitous fibromyalgia...which again, I contend is a symptom which needs to be followed up on....For me this finding narrows the small fiber neuropathy focus....from wide angle to zoom.

I am mortified about 'anticipation'....those of you who have done any genetic reading know about that.

My doc, whom I regard as some 'archangel'...and I do not say that much about docs....he is human, he grumps at me now and then, but not much...has gone with me on this. I have had several very, very good docs, who went way beyond the call of duty....recently. I know he is frustrated and would like to get to the bottom of this too, as it is an enigma, and I am tenacious...and he has the staff and tools...and he is tremendously compassionate, infinitely intelligent, and well, nice. I have had some tremendously patient, intelligent minds work on this, from the pathology to the surgery to the case coordination.

I am not dying, and I can't lose sight that these docs take care of people every day, who get very bad news...and need a cure immediately. At times I feel too lucky to have these wonderful docs, yet, I have had my share of heartache too, and hope for some consideration.

When you get into these new categories they do not want to narrow things too fast, and give the wrong diagnosis, when a new disease or entity could be hiding over the hedge....it takes patience, which I have little of.

I went thru almost a 2 decade drought of real duds...we have all been there...remember, when it was in your head???

I forgot, I actually had 4 biopsies...I forgot the fat aspiration for amyloidosis, which was negative...thank heavens.

There are a few hereditary diseases that jump right out at docs....then there are the less frequent ones, then the rarer ones, then the huge mess of idiopathic oddities from which these docs try to glean similar tissue types...then I imagine similar gene mutation loci.

That jump from tissue type to gene can't be a leap of faith based on clinical findings....it boils down to misplaced adenine, guanine, cytosine, thymine...and in RNA uracil.....somewhere amongst millions of pairs, there are the mismatches, the repetitions. Picky, picky work done by very smart people who can deal with all that monotony and highly detailed work.

And yes, we all carry some mutations...that is evolution.

No one is perfect...not yet!! (Hopefully never:eek:)