Mosaic Klinefelter's

[Serenation]

Hi does any have any experience with mosaic dna. I've been told all my life by doctors and endo's that I have klinefelter's though my DNA tests done from blood cells show otherwise. I have like 95% of the klinefelters symptoms and was diagnosed with androgen deficiency in my late 20's when it had become quite obvious that I was not just a late bloomer. I was having real trouble trying to pass as male and being bullied and discriminated against constantly for not being normal in a rural town.

It was at that point I had my hormones balanced to female as that is the gender I always felt, I did not want the recommended testosterone shots.

so 12 years later Here I am, still wondering if I have brain tumours, mosaicism or some other explanation. I am finally getting an MRI done next week to see if tumours are present.

I'm not fully educated on whether there is a single good reason to know other than to stop me wondering, it will have no effect on the choices I made. On the bright side I'll officially know which sub section of the forum I'm meant to post in.

[HughE]

Serenation,
If your gene test came back normal, then it's probably not Klinefelters, but just a case of your doctor trying to fob you off with the first diagnosis he could come up with that remotely fit your symptoms. Many of us do have signs of hypogonadism and can physically look quite a lot like Klinefelters patients, even prior to starting any HRT.

Do you want to have children at some future date? If so, then I'd suggest going to a fertility doctor and find out whether you're actually suffering from secondary hypogonadism. If so, with the appropriate treatment it's very likely you can produce some viable sperm that can be frozen and stored for future use. Once you start on transgender HRT, even without an orchie it'll be much harder to do that.

As to what caused your condition, did your mother experience any problems during her pregnancy with you that resulted in her being given intramuscular injections? If so, then it's quite likely that your mother was given synthetic female hormones (estrogens and/or progestins), drugs which, based on my own experiences and what I've seen over the last 3 years of the effects of a drug called DES, can cause a range of intersex-related disorders including gender dysphoria and transsexuality.

If you're interested, here's some further reading:
https://www.susans.org/forums/index.php/topic,157142.0.html
https://www.susans.org/forums/index.php/topic,84224.0.html
https://www.susans.org/forums/index.php/topic,157295.0.html
https://www.susans.org/forums/index.php/topic,159978.0.html

[MileyOrnot]

Usually you only check two cells when testing for Klinefelter Syndrome because it's cheaper.  They need to examine at least 20 cells to determine Mosaic Klinefelter.  Is that the test you had?

http://www.genome.gov/19519068

How is Klinefelter syndrome diagnosed?

A chromosomal analysis (karyotype) is used to confirm the diagnosis. In this procedure, a small blood sample is drawn. White blood cells are then separated from the sample, mixed with tissue culture medium, incubated, and checked for chromosomal abnormalities, such as an extra X chromosome.

The chromosome analysis looks at a number of cells, usually at least 20, which allows for the diagnosis of genetic conditions in both the full and mosaic state. In some cases, low-level mosaicism may be missed. However, if mosaicism is suspected (based on hormone levels, sperm counts, or physical characteristics), additional cells can be analyzed from within the same blood draw.

[Serenation]

Thanks HughE, it was suggested I had klinefelters from around 8 doctors including specialists that run Australasia's largest trans services. Not just a random GP. I transitioned 12 years ago, so even if there was a possibility of having children back then there certainly is not now.

My mother did not have any hormones while pregnant, though hormone imbalances runs in my family both sides. I'll spending some time now reading the links you provided thank you.

MileyOrnot thanks for posting I had 15 blood cells tested. This is where it gets confusing as there is contradictory information online. Your link says only blood cells need testing, others say you can have xy blood and xxy skin cells etc, there are people who have different dna in each eye.

"In other individuals, it is more difficult to diagnose mosaicism.  For example, a blood test would not be able to diagnose mosaicism if the chromosome change is only located in the skin cells.  In cases like this, additional testing may be needed to detect mosaicism.  Usually, this would involve examination of other tissues of the body, such as the skin.  A geneticist can help determine whether this type of additional testing is appropriate." - http://www.chromosome18.org/WhatisaChromosome18Abnormality/TheConditions/Mosaicism/tabid/490/Default.aspx

[Alexis Paige]

Have you ever heard of androgen insensitivity syndrome?

It is a condition that hase multiple grades that vary from appearing completely female from birth but with 46XY chromosomes to completely male but with decreased fertility. For a number of grades there is genital ambiguity, but not all.  Further  grade 1 or 2, where you would probably fall, has very little known about it.

It is very hard to diagnose though.  Common symptoms would be under masculization during puberty, infertility, average to slightly elevated testosterone,  lh, and estradiol levels. Because of this it can be hard to diagnose. There is another specific genetic test to look for mutations to the ar gene that can be done, but studies have shown that between 27-70% of people with partial ais, the mid to lower grades, will not be detected by that test.

If it is this you may never know for sure. That's where I am.  I have a similar story to yours,  but I've only recently started hrt. I also had to actively work to be read as male.  In fact, my body feminized during puberty to the point where I passed as female 100% without hormones. I've even had multiple doctors think I'm intersex in some way, but never give a confirmed diagnosis. 

I understand wanting an answer to why your body isn't standard. It's not as a reason to justify being trans. It's because there is obviously something different about you but you don't know what it is. Its for peace of mind from being a mystery.

I guess I'm really posting to let you know, if you never get an answer your not alone in always having to wonder.

Edit: I guess because I'm feeling insecure that people will think I'm exaggerating,  here is a pic: http://i.imgur.com/g5tJMld.jpg?1
This is me basically without hrt,  1 week of estrogen. I don't pad because I grew breasts and developed that waist to hip curve during puberty. I also don't tuck because its to small to be noticed.

[Umiko]

is there a certain doctor that tests for this? i was reading into it since i was hearing about it a lot and it could possible explain why i hit puberty so late though when i got my hormone panal back it showed a somewhat low but in the average range counts o.o

[Serenation]

Thanks Alexis I have read some about the AIS the levels and some of them did certainly fit for me. I agree that it has nothing to do with me being trans. Nice to know someone else understands why I'm pursuing these tests.

I was around 5 when I started to question my gender so I consider this a separate issue to me being trans.  It wasn't till I didnt get secondary sex characteristics that I knew there was something physically wrong with me. Some people still mistake me for a teenager girl and Im 40. Same story with me is that I struggled passing for male, HRT gave me boobs and made me my mental state much much better (yey for balanced hormones) but no major changes other than that.

Umiko you can read about Androgen defficiency here http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Androgen_deficiency If your in the lower range of normal, I guess it's still normal, the minimum range for male testosterone is 250 from memory and the range for female is 15-75 from memory.

Being tested for klinefelter's itself is just a blood test or even mouth swab (?) that you GP can organise, depending on your country it may or may not be free (I paid around 300 dollars for dna tests)

[Umiko]

i have really good insurance and my GP is in internal medicine so my test are usually paid for in full. can an endo do this test to? i see one this wednesday for further testing

[Serenation]

i have really good insurance and my GP is in internal medicine so my test are usually paid for in full. can an endo do this test to? i see one this wednesday for further testing

Yes your endo is the perfect person to ask! that's who a GP would refer you to.

[Umiko]

awesome. i'll ask for them to do the test and hopefully rule it out though

[HughE]

Thanks HughE, it was suggested I had klinefelters from around 8 doctors including specialists that run Australasia's largest trans services. Not just a random GP. I transitioned 12 years ago, so even if there was a possibility of having children back then there certainly is not now.

My mother did not have any hormones while pregnant, though hormone imbalances runs in my family both sides. I'll spending some time now reading the links you provided thank you.

MileyOrnot thanks for posting I had 15 blood cells tested. This is where it gets confusing as there is contradictory information online. Your link says only blood cells need testing, others say you can have xy blood and xxy skin cells etc, there are people who have different dna in each eye.

"In other individuals, it is more difficult to diagnose mosaicism.  For example, a blood test would not be able to diagnose mosaicism if the chromosome change is only located in the skin cells.  In cases like this, additional testing may be needed to detect mosaicism.  Usually, this would involve examination of other tissues of the body, such as the skin.  A geneticist can help determine whether this type of additional testing is appropriate." - http://www.chromosome18.org/WhatisaChromosome18Abnormality/TheConditions/Mosaicism/tabid/490/Default.aspx

I don't see how they could make a definitive diagnosis of Klinefelter's if all your genetic testing came back negative for the condition. More likely all 8 doctors were just going along with the initial diagnosis because it meant less work for them, and because they didn't want to discredit their colleague. A lot of the time, doctors act more like a secret society whose first loyalty is to each other and to maintaining the good name of medicine!

[Serenation]

They never officially diagnosed it, they just said stuff like I'm pretty sure you have klinefelters, you look like you have klinefelters, we think you have klinefelters, it was after I brought them the DNA test that they said ok you don't have klinefelters (the specialists in Australia were not familiar with the mosaic variant) and said well it can also be a benign tumour affecting the pituitary gland.

I'll check off as many boxes as I can. Not only for myself but to help with research if it's something uncommon.

[Sydney_NYC]

They never officially diagnosed it, they just said stuff like I'm pretty sure you have klinefelters, you look like you have klinefelters, we think you have klinefelters, it was after I brought them the DNA test that they said ok you don't have klinefelters (the specialists in Australia were not familiar with the mosaic variant) ......

I had the same experience. My HRT doctor brought it up. (She handles many MtF patients.) She told me that with the mosaic variety, it can be difficult to detect because some parts of the body are XY and others are XXY and there is no way to know which part has which variant. She did said that it doesn't make any difference with HRT as she will be monitoring hormones and it anything, it helps and certainly doesn't hurt, so way spend the money on testing unless you just want to know.

[Ms Grace]

...it can be difficult to detect because some parts of the body are XY and others are XXY and there is no way to know which part has which variant...

Well that's weird... how does it even work?

[Serenation]

I had the same experience. My HRT doctor brought it up. (She handles many MtF patients.) She told me that with the mosaic variety, it can be difficult to detect because some parts of the body are XY and others are XXY and there is no way to know which part has which variant. She did said that it doesn't make any difference with HRT as she will be monitoring hormones and it anything, it helps and certainly doesn't hurt, so way spend the money on testing unless you just want to know.

Hi Sydney. Happy to know some Docs are versed in it. Yeah I'm still curious to know, but there will be a financial limit. it is more than likely something else that will show up in the MRI.

Ms Grace at is basic form it's errors on cell duplication, can read about it here.http://en.wikipedia.org/wiki/Mosaic_(genetics) Interesting that someone has different colour eyes, now I'm thinking about puppies, I think different colour eyes is quite common in Alaskan Malamutes

[Sydney_NYC]

Hi Sydney. Happy to know some Docs are versed in it. Yeah I'm still curious to know, but there will be a financial limit. it is more than likely something else that will show up in the MRI.

Ms Grace at is basic form it's errors on cell duplication, can read about it here.http://en.wikipedia.org/wiki/Mosaic_(genetics) Interesting that someone has different colour eyes, now I'm thinking about puppies, I think different colour eyes is quite common in Alaskan Malamutes

That's exactly how mosaic works. It will not show up on and MRI unfortunately (unless they can see different shaped lungs or kidneys.) My wife's aunt was mosaic, she had different color eyes. For me, I have two different shaped feet. There have been variations to where some individuals have different color skin patches across their body. Sometimes it's just more evident than others. Side note: All calico cats are mosaic and female. If they appear male, they are intersexed.

[Serenation]

Thats pretty interesting about the cats, and I hope your feet are not so different that it's difficult to buy shoes.

Some causes for Androgen Deficiency

Testes – medical problems that affect the testes can prevent sufficient testosterone production. Some of these conditions are present from birth (for example, Klinefelter's syndrome, a genetic disorder where there is an extra sex chromosome in the body's cells). Other conditions may occur at various stages of a boy's or a man's life, such as undescended testes, loss of testes due to trauma or 'twisting off' of the blood supply (torsion), complications following mumps, and the side effects of chemotherapy or radiotherapy.

Pituitary gland – the most common condition that affects the pituitary gland and leads to low testosterone levels is the presence of a benign tumour (adenoma). The tumour may interfere with the function of the pituitary gland, or it may produce a hormone that stops the production of the gonadotrophins, the hormones needed to signal the testes to produce testosterone.

Hypothalamus – particular conditions, such as tumours or congenital abnormalities, can prevent the hypothalamus from prompting the pituitary gland to release hormones. This will inhibit testosterone production by the testes. This is a rare cause of androgen deficiency.

The MRI is to check for the last two.

[Sydney_NYC]

Thats pretty interesting about the cats, and I hope your feet are not so different that it's difficult to buy shoes.

Fortunately they are the same shoe size in length, but my left one is a little wider than the right one.

[JLT1]

HI,

People with Klinefelter's Syndrome typically have most of their karyotype being 47, XXY and about 20% have higher order mosaicism such as 48,XXXY or 49, XXXXY.  Typically, the higher order the mosaicism, the more the brain (e.g. speech) is affected.   The key point to this post is the people with "most" of the karyotype being 47,XXY.  There are other types of mosaics btw...

My favorite article on this, what I'm about to describe, was published in the Journal "Lancet", (p 494, 1965, Letters to the Editor, Lonsdale).  While that article focused on a hermaphrodite I don't want to address that focus.  I want to focus on the genetics explained in that article because that concept could have broad applicability to those identified with Klinefelter's and perhaps even some who have not been diagnosed with Klinefelter's. 
In the article, the patient had the following karyotype: of 64 cells analyzed, 49 were 46,XX, 8 were 46,XY and 7 were 47,XXY.  It was hypothesized that "this mosaicism could perhaps result from an initial XXY zygote with posteriorly a double mitotic loss of an X and a Y chromosome." This double mitotic loss would occur during embryogenesis. I have also seen this same explanation for other distributions in other journal articles and in one genetic textbook and I have seen several other papers on people with a similar profile in their karyotype (e.g. and more : Exp Mol Pathol. 1999 Sep;67(1):50-, although they did not include an explanation).  I also noted more than one article that talked about the fact that the  karyotype of different tissues could be different.
On the basis of my rather limited knowledge of genetics, I hypothesize that individuals identified as having Klinefelter's could in fact have organs that are predominantly 46,XX or 46,XY or 47,XXY and be a more or less typical female or male.  However, they could something like 46,XY in the body and 46,XX in the brain.

When they tested me they took six 1" skin samples (two on upper back, two just below my breasts and two on my arms).  They analysed a lot of blood cells.  They ran DNA and Karyotype of all samples.  Anyone can do the karyotype analysis, I have a list of labs that can do the mixed DNA analysis if that is needed as well.  (Not all labs can do that).


Hugs,

Jen

[Serenation]

Hugs thanks Jen that was very indepth, also makes it pretty clear it's highly possible that people who have it will never be diagnosed. All i know so far that I have 15 blood cells that are XY

I'll update this little journey of knowledge as I go, MRI scan in 3 days.