[tri-med] Re: testing of cells results/Karen

I am so grateful for your response. I ma begginnig to understand some of
this finally. Your email was not to long. There is never to much info when
it comes to my kids. I will be calling my genetic docotr on monday, but with
this I will have the ability to ask better questions. I do realize the
outcome is often the same with full or mosiacism. Our sons severe
abnormalities tell us his chances are low of survival no matter the defiante
diagnosis but I just want to know.

Here is someof the info you asked for:

They tested amnio fluid not blood

FINAL CYTOGENETIC ANALYSIS:
47, XY, +18    (5 cells)

Cytogenetic analysis of cultured amniotic fluid at 400-450 band resolution
showed a male karyotype with an extra chromosome 18. This finding is
diagnostic of Trisomy 18 syndrome.

My understanding is that in the FISH test they tested 100 cells. I do not
know if that makes any difference. Also I live in Canada not the US so I do
not know if how they do things here is different then there.
The flask thing I have not clue about but will ask the doctor when I call.
I thought testing 5 cells from the full amnio (cultured) results seemed
small but I thought it was becasue the FISH test they did 100. Should they
be testing more cultured cells??
I am alittle nervous about asking for retesting here becasue medical is very
different then in the states(I am an american living in canada).
Thanks for all your help and time
Sandi


----- Original Message -----
From: "Karen Schuler" <karens@xxxxxxxxxxxxxxxx>
To: <tri-med@xxxxxxxxxxxxx>
Sent: Sunday, March 24, 2002 12:27 PM
Subject: [tri-med] Re: testing of cells results


>
> ----- Original Message -----
> From: "Aaron & Sandi"
> > My question is does this mean the other 18% of cells are normal??? and
do
> not contain an extra 18
>
> You can ask almost anything here and someone will have some experience,
but
> you really need to speak with your geneticist as well. I can give you some
> answers, and lots of questions for your geneticist.
>
> The answer is maybe this is a case of mosaicism for trisomy 18 and
probably
> not for the sex. What you really need to find out though is what the
> g-banding or cultured results show.
>
> The result that you have given is the result of a FISH test (maybe a SKYE
> but I would guess a FISH). Although they are widely used these days they
are
> still considered either experimental or at risk of innacuracy and so any
> results from a FISH test must be confirmed with a cultured karyotype. I
will
> explain why in a minute.
>
> The cultured karyotype ALWAYS takes precedence over the FISH. So if the
> cultured karyotype says 100% of cells showed T-18 they will consider the
> result full T-18. If the cultured cells showed even 1 "normal" cell they
> will consider it mosaicism.
>
> They may redo the test, and they may suggest other testing to confirm the
> results, eg if this prenatal they can either redo the amnio, do a PUBS (or
> cordocentesis - very high risk to the baby though). If this is after birth
> they may repeat the blood test and suggest a skin biopsy.
>
> With the results that you have there are a lot more questions I would need
> to know to give any real answers, and these are probably best answered by
> your geneticist anyway. (For example what sort of probe was used, how many
> cells were studied, what medium was studied, how many flasks etc) But in
> general terms
>
> 99% of the cells showing both an X and Y chromsome is pretty much
definitive
> that the baby is a boy - 1% not showing both X and Y is simply statistical
> variation. The signal in the cell or cells not showing both the X and Y
> probably just "faded" very quickly.
>
> 20% of the cells not showing an additional 18th chromosome is not so clear
> cut. It may be statistical variation it may be mosaicism.
>
> Personally I would be leaning towards mosaicism.
>
> If it were me I would be asking for a repeat test to confirm either way
> (depending on risk factors and your own personal feelings) and I would
> definitely not be judging anything about this baby except the babies exact
> medical status.
>
> My own personal experience (that is talking to lots of other mums with a
> prenatal diagnosis of mosaicism) tells me that mosaicism percentages via
> amnio are usually higher than after birth. eg IF (big IF here) this IS
> mosaicism and its 80% in an amnio then the number of T-18 cells detected
> after birth, in blood will be much less. I would guess somewhere around
50%.
>
> Percentage of course does not mean that the baby will not have problems,
> statistics on survival with mosaicism are really not much better than with
> "full" T-18 and that life wont be hard. But it does mean that its easier
to
> argue with the doctors about quality of life and the prognosis
> developmentally is usually "better".
>
> Although we like to think of cytogenetic tests as being is infallible this
> is not the case. Doctors can and do make mistakes. Test results are not
> always 100% accurate.
>
> With a FISH test the chromosomes are prepared and then painted with a
> "paint". A probe is then added to the cells that matches to the cells that
> they are testing for - in this case 18th chromosomes. The probe ONLY picks
> up signals from the chromosome, or part of the chromosome that it is meant
> to. For example an 18th chromosome probe will not show you that there is
an
> extra 17th chromosome (or missing 17th chromosome). This is why the
doctors
> MUST know what they are looking for.
>
> There is a rapid test FISH probe that is done. It detects 18, 13, 21 and X
> chromosome problems - but this is fairly new and still only looks
> specifically at these chromosomes no other. (each chromosome comes up in a
> different colour - very pretty)
>
> A FISH probe cannot show you if the signal is part of a chromosome and
other
> finer detail. This is one reason why it must always be confirmed by a
> cultured karyotype. So for example a FISH test will not show you if the
> problem is a partial trisomy 18 unless they are looking for a very
specific
> break point, but thats a different type of probe all together.
>
> The glowing light that they read to count may not "take" to a few cells
and
> it also fades fairly quickly, this is the usual reason why FISH tests will
> show a false mosaicism result. Under normal circumstances you would expect
> any sample to lose the signal from a few cells, as with the X and Y. This
is
> statistical margin of error.
>
> Losing 20% or there abouts of signals (especially when you only lost 1%
off
> the sex cells) is getting a little high. It may be statistical variation -
> it may be true mosaicism. You will need to discuss this with your doctor
and
> the lab as to what they accept as statistical error. There are NO
universal
> standards for this, each lab makes their own rules.
>
> Also what you were told by the doctor can depend on what sort of doctor
told
> you. Obstetricians for example often have little or no knowledge on the
ins
> and outs of genetics. Many wouldnt know the difference between full,
mosaic
> or partial if it turned around and bit them!!!!
>
> This signal is seen as a pretty coloured glowing light. The doctor must
then
> manually count how many signals that they see - in this case 82% of the
> cells that they looked at had 3 signals instead of two from an 18th
> chromosome.
>
> There was another family on the list (HI!!!) for whom I had this
discussion
> with my favourite and world respected cytogeneticist (a cytogeneticist is
> the person who literally does the chromosome test). She was happy to
accept
> up to 5% as a margin of error in most cases (in 500 cells), but would
still
> report it. However she didnt like the standards for the lab I was asking
her
> to give a second opinion on. She would give them at least 10% probably
> higher on the margin of error before asking for a retest. Additionally the
> cultured karyotype showed full trisomy 18 (only 20 cells).
>
> The second opinion verdict, even though the FISH showed mosaicism of 11%
> (that is 11% of cells had a normal 18th chromosome signal) that we needed
to
> consider that the child had full T-18. Retest was not possible as the
child
> had passed away.
>
> Now that is probably a longer and more complicated answer than you were
> asking for - sorry. And I noticed after glancing at a few mails that we
now
> have a resident lab person on board that may give us both some better
> insight.
>
> But the bottom line from where I am sitting is that yes this may be a case
> of mosaism but it may not be.
> If you have the results I would love to know - what the medium was that
they
> tested (eg is this blood or amnio). How many cells did they test? (eg 5,
20,
> 100, 500) How many flasks did they test? (eg if they tested more than one
> batch of cells from the same sample - this equates with something called
> mosaicism grade)
>
> And of course what were the results of the cultured karyotype? How many
> cells did they sample? Were the cells that they tested fragile? or
different
> in anyway?
>
> BTW cultured karyotypes can also be wrong - ask Alex about that one. His
> original test after birth showed 100% normal cells - second test showed
60%
> of cells with an extra 18th chromosome. Third test showed 80% of cells
with
> an extra 18th chromosome. FISH test on skin showed no cells with an extra
> 18th chromosome but we havent repeated that one, it hurts and leaves a
> scar..........
>
> When people ask me, a mother with experience of mosaicism and who went
> through the wrong result route, and also as someone who has spoken with
lots
> of cytogeneticists and geneticists about mosaicism but who is NOT a
doctor.
> I always recommend that families ask for a minimum of 100 cells to be
tested
> by a regular cultured karyotype from at least 2 different flasks. With
FISH
> testing I recommend that they screen at least 500 cells at a reputable
lab.
>
> If there is any doubt about the test results I would always go with the
> "better" result (better than going with the wrong result) until it is
proven
> otherwise. Remember you also have the right to ask for the test to be
> redone. I have seen way to many errors in genetic tests to be comfortable
> with just accepting that these tests are 100% reliable. They are most of
the
> time - please dont get me wrong, but there are so many factors involved
and
> they can and do make mistakes.
>
> I guess in some ways I have never gotten over the fact that a mum here in
> Australia had an amnio that showed T-13. Like the vast majority of people
> she went ahead and interrupted the pregnancy. Unfortunately the autopsy
> showed no physical signs of T-13 and neither did the culture done at the
> autopsy.......................
>
> Man must not allow the clock and the calendar to blind him to the fact
that
> each moment of his life is a miracle and a mystery.
> - H. G. Wells
>
> Keep Looking for Rainbows!!!
> Karen, Mum to Alex (7, T-18 mosaic)
> Sydney, Australia
> http://members.optushome.com.au/karens
> http://www.trisomyonline.org
>
>                   Building ___ooOOoo__ Rainbows
>                        www.trisomyonline.org
>                   Families Helping Families On-line
>

                  Building ___ooOOoo__ Rainbows
                       www.trisomyonline.org
                  Families Helping Families On-line

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