Can an amnio be wrong?

[Louloumay89]

Bit of background: I had an amnio and microarray due to my baby's heart problems that were found on the 20 week scan. Results came back clear.

Baby is now 6 weeks. She was born at a low birth weight and has hearing loss in both ears.

Pediatrician suggested she has a blood test in case of a genetic cause. I told her I'd already had an amnio and she replied maybe the results were wrong - i.e my DNA was tested instead of the baby's.

I feel absolutely floored. Has anyone heard of this before? She said she'd discuss it with a colleague in genetics before she refers dd for a blood test (poor dd has had so many procedures recently).

Genetics is a masssssive thing, we had a Microrrary done after ds was born which was 'normal' but after several more tests they did discover a rear genetic condition that wasn't picked up.

Thank you. I think I naviely thought we could discount genetics but it sounds like a blood test may be the next thing.

An amino test shouldn’t be wrong but like any medical procedures mistakes can occur and if there are concerns it’s best to double check. Hope all goes well x

I thought an Amnio only checks for a few specific genetic anomalies. There could be a zillion more that weren't checked for. As the parent of a child with a rare genetic disease, I am constantly overwhelmed by how much I don't know or understand about genetics (and I even studied Biology at University and have two Professors of Biochemistry parents to consult with).

@sofiaames An amnio does typically check for the 3 main trisomies only yes but the OP stated they had a microarray which examines the entire genome and should detect any genetic abnormalities.

You are right, but....Having just had a big fight with ds' insurance company about updating his genetic testing, I have recently learned that microarray does not give the whole picture because it only looks at deletions (I hope I got this right) and that you also need to do Whole Exome testing which looks at genes that are out of order. My analogy is (please tell me if this is off)....Microarray is like running spell check and Whole Exome testing is like getting a friend who can spell to double check for things like "there" and "their" that wouldn't get picked up in spell check.

Ugh. Ds has mitochondrial disease and they didn't even know that mitochondria had dna when I was at university. I really need to do a refresher course.

Microarray testing only tests for the set of abnomalities 'dotted' on that individual array pattern.
Exome sequencing is the coding sequence only
Some functional mutations are in the non coding (introns)
Whole genome sequencing gets the lot but takes an age and is more expensive.

@sofiaames Yes you are correct it wouldn’t pick up if the genes were in the wrong order. It picks up duplicated or missing genes.

There is a big misunderstanding here.

A microarray is not a whole genome sequencing. It doesn't look at mutation inside a single gene. Duplication (two copies of the same gene) or deletion (gene is missing), yes, but even for those, it might be missed in the mosaic forms.

Only genetic testing, for a specific gene can give you an answer, but you need to know before hand which gene you want to look at.
You cannot do a whole genome sequencing to look for a genetic defect. It is still a massive task costing a fortune.

So it is not that the amnio was wrong, but more that the microarray didn't pick the specific gene mutation/deletion/duplication/splicing and so on.

The prenatal consultant should have given you a better explanation of what that test could and could not detect. Let me try to explain it to you in very simple terms.

Consider a big wall with 20.000 books (the number of genes in the human body) . You can count the books, notice if one is missing or if you have a double copy of one of these, but unless you pick up the book and open it, you cannot know if there was a misprint, say the first chapter missing, or page 123 is printed upside down, or if there is a spelling error in the last chapter.

Microarray is the person counting the books. It can detect if the whole Romance section is missing or if you have two bibles, or if someone took the Atlas away but it doesn't open the books, nor go through all the pages, line by line, word by word for every single book. That can only be done with a genetic test, for a very specific gene.

I have a genetic disease called NF1, which is the name of the gene. There are more than 4000 mutation types (and counting) and no way of connecting the mutation to the severity of the cases. A microarray can only detect whole gene deletion in NF1, so 5% of all the case, not any of the other variants. a microarray wouldn't have picked my genetic disease.

Back to you and what happens next: Bases on symptoms present (heart, hearing, ....) and as important symptoms absent, the geneticist will have a list of possible genetic issues and when requesting the genetic testing, he/she will require it for those specific genes.

Good thing is there are massive advance in genetic management and even genetic correction in a not so far future. Genes are no longer destiny, epigenetics, the environment in which genes are expressed and silences can be modified.

Go one step at the time and if you need more info on genetics, genes, mutation, just ask, it has been my day by day for years now.

KingIrving thank you!!!!! for that most excellent analogy. I have been trying to get my ds' geneticist and my parents to explain this and have spent hours listening to sophisticated genetic explanations that have left me none the wiser. One of the big problems is that most doctors study little to no genetics in medical school. That is changing, but not fast enough!

Whole Exome testing is becoming much cheaper and more possible and only takes 4 months these days so there is actually an expectation that it will get paid for by insurance which is why we are trying to get it done for ds now. When he had his original testing 5 years ago, it was not available. Lineagen in Salt Lake City Utah are doing this type of testing.

Good luck with the insurance.

I had a look at the company you mentions and they don't do a genome sequencing of all genes but only those genetic variants that are associated with disorders of childhood development and recommend san additional list for tricky ones that cause cancers or chronic diseases. Funnily enough, in this list NF1 is not present, but NF2 is.

So for someone like the OP's child with a heart defect or hearing loss, the whole sequencing is still far away. Technology is changing, it takes so many datas , it is a huge task.

Another thought: try to let go just a little bit: with four little ones it can’t be only you and you all the time.

I have triplets and prepared myself mentally in pregnancy already that it was better for others (nurses, doctors, DH, MIL, etc) to give love and care to my DC in parallel to me than me trying to do it all.

Apart from all the technical information a friend of mine was told that her foetus had all kinds of health problems, including water on the brain, and then three weeks later it turned out that the laboratory has done the test wrongly.

Congratulations on your baby, OP, I hope she is clear of all other health problems.

That happened to a friend of mine too, but it wasn't a mistake, it just was that there was a chance of issues because of a particular genetic marker, but in fact there were no issues.

We have higher risk for a specific genetic issue and were told that if we had amnio we would have to have more than the standard test run on it, something called FISH? So I think yes certain issues can be missed unless they are specifically looking for them. Even that would have taken weeks so I think to screen for everything they know about would definitely not be a standard test.

Very interesting, genetics is fascinating! And as a previous poster said not taught enough. I was under the impression microarray would pick up the vast majority of abnormalities, I guess as we learn more about the human genome we realise there’s a lot it can’t detect.

Not wrong but the micro array doesn't pick up every thing. I had a cvs in pregnancy , they told me my baby was fine . He isn't ! .. he is now 7 with fairly severe special needs .

Also my son clearly had a genuine issue and the micro array didn't find anything . I had no idea when I was pregnant that these things happen. I guess you never think it will be you but it has to be someone 🤷‍♀️.

Genetic