Options for genetic testing

Would this still be your answer now, 5 years on, @Jonathan Edwards ?
Or would you say have there now been enough / any advances in research / understanding that would mean you'd give a different answer today?

I'm thinking specifically about if there are conditions / diseases / illnesses (whatever the correct word or words are!) that can be picked up through genetic sequencing (not necessarily 23 And Me specifically), but that would not be easily found on the "standard" set of blood tests that would (ideally) be run today for someone with M.E/CFS presentation.

 

IIRC, 23andME doesnt do the testing themselves, they order it through a company. And you can order your testing directly though that company too, where they will give you the raw data aswell as their analysis.

 

Yes.

 

My daughter is waiting to see a neurologist to find out whether she has a particular genetic condition called myotonia congenita. It seems likely that she has it, or something in the same area (non-dystrophic myotonias), but the proper medically recognised genetic testing that is available has to be ordered by a specialist or genetic counsellor, and the wait for that is going to be long.

Is there any direct-to-consumer test that would give an answer in the meantime? She realises it could not be used for diagnosis, and that it might be lower quality than the testing she will eventually get. It's just the "not knowing" that is getting to her.

I'm guessing the answer is no but it's hard to watch her sitting at home, unwell, waiting yet again for help with another rare condition that could be effectively medicated if someone would let us pay for a couple of genes to be tested now. Although I suppose the medication would have to wait for the official diagnosis.

 

I know it's not what you want to hear, but no.

It must be incredibly hard for her, and for you as a parent, but maybe look at it this way: most direct-to-consumer tests were set up with the aim of profiting from people's genetic data, not to advance diagnosis or treatment.

There's no one-size-fits-all screening panel because they need to look in high resolution at the relevant locations. From what I understand, to do work that detailed on a whole genome would be a bit like using a microscope to search a city for the restaurant you want to visit.

Your daughter would be giving up control of her most personal information—and some of that of her close relatives—without even knowing what's going to be happen to it. She won't get a reliable answer, or any medication, so there's no benefit for her.

Could she maybe get support from online forums for the condition she's suspected of having? There must be lots of others who've endured the same frustrating wait, and sometimes just knowing that other people understand genuinely helps. People come here knowing there are no answers for ME/CFS (yet, anyway!), but it reinforces that they're not suffering alone. There's always someone to say "I hear you, and I'm thinking about you".

I'm really sorry she's gong through this, and I hope she doesn't have to wait too long.

 

For doctors there is a screening panel they can order. You need the specialist to choose the right selection of panels in case it is not the diagnosis you mention, but one very similar.

You can do a screening by ordering WGS yourself and then using an open source tool such as gene.iobio to screen for the condition phenotype and the associated genes. But for 99% of people it is best left to the experts to run the right tests as it is a complicated analysis to learn from scratch. And at the end of the day the depth of the genetic reading is much deeper with the screening panels, so that would need to be run anyway.

I checked my WGS data on gene.iobio against the myotonia congenita phenotype. It highlighted that I am heterozygous for a missense on SCN7A - the 14th gene listed on the myotonia congenita phenotype. But that doesn't mean I have it. In fact, SCN7A is more likely to be associated with neuropathy, and then again only if I were homozygous for it. So as you can see even if you order your own WGS it is still very difficult to use and understand. That's why we pay the experts.




According to a gene site (link) CLCN1 is the main gene of interest and I don't have a variant of that. And that site said there are a lot of tests a neurologist can run as well which may be needed.

Just to add, I have a family member who is very ill too. I ordered them a WGS testing service in 2023. The kit was sent to my family member who provided the spit and sent off the tube. They never got their WGS data or a refund despite an inordinate number of complaints. There are some dodgy players in this field.

 

@Kitty , thank you for the thoughtful reply. I joined a couple of support groups on Facebook (my daughter doesn't have a Facebook account because she says it is too annoying) and I posted a couple of questions and comments.

Unfortunately, one of the key people on one of the groups made a statement that it was not her "intuition" that my daughter had myotonia congenita. Not sure why she would make such an unwise statement with no basis. My daughter is an avid reader and she's narrowed down the possibilities very well. There are not many conditions that can cause generalised muscle hypertrophy in a sedentary adult. She's also had testing to rule out other possibilities (acromegaly, excess androgens).

But I'm a grumpy, cynical old journalist and my daughter has pre-diagnosed herself correctly four times so far (she awards herself a Fauxbel Prize in Medicine each time), so we took it with a grain of salt.

So that group is not much help, although we have read through it and found some common ground with her symptoms. I also joined another group, who are much more friendly, but reading posts there made us realise it doesn't fit her symptoms very well. Too bad you can't choose which disease you have according to how balanced the support group is!

I do agree about the privacy and information-selling concerns with sending off your DNA to a commercial company.

We are on the cancellation list with the neurologist, so perhaps we will get in sooner. Fingers crossed.

 

@wigglethemouse , it is complicated, isn't it. I'm sorry to hear that your family member never got their data or a refund.

I think the neurologist will order panels for myotonia congenita, other non-dystrophic myotonias, and perhaps myotonic dystrophy as well. And they will do an EMG, although mysteriously some patients with demonstrable myotonia symptoms have normal EMG readings. My daughter only has what might be myotonia first thing on getting out of bed, when she has trouble getting her legs moving. But I doubt he will turn up at the house to measure that!

If it does turn out to be genetic, then there will be the matter of who my daughter inherited it from. If from her mother's line, there are no implications as no close relatives left. If from my line, then there are a lot of people who would need to be alerted. This is because even people with no symptoms of myotonia congenita can be susceptible to a life-threatening reaction to certain general anesthetic procedures. So that will be quite a process.

 

Yes, that is a good idea. I saw the FSHD study and clicked through to the website. What a valuable service to patients and research.

There seems to be a reasonable amount of myotonia congenita research ticking over, including existing drugs being tested for possible repurposing to use in myotonia. And it's comforting to see that there are about five or so current drugs for treating it. Always good to have a choice in case one drug proves ineffective or has unacceptable side effects.

 

And having said all that, the genetic testing may not give a clear answer. People sometimes find out that they have a variant of unknown significance on the myotonia congenita gene, and then have to wait until more research data comes in and that variant is "upgraded" to being diagnostic, if that's the right term.