Genetic testing for 4 year old - Neurofibromatosis?

[Dustyblue]

Hello All,

I'm in a bit of a state about this. My DS4 was assessed by a paediatrician last week, for poor fine motor skills and a lack of adjustment to starting kinder this year (we're in Oz, they do 4 year old kinder then start school at 5-ish). Long story short, that part of the assessment went fine. A few things to work on with an OT but nothing dire.

The Dr also noticed that DS has quite a few 'cafe au lait' spots (he had them at birth, but I think a few more have appeared since). Also that DS has a large head (55cm). Both things that have noted before.

Now I've a referral for a blood test to do a genetic screen for 'NF'. No type or testing for variants, just 'NF' I've studied genetics but not extensively, however I have a basic understanding of what NF is. There are 2 types, one milder, there are variants etc.

I would devour more data now (have a post-grad research background) but am too fragile & am leaving my usual research sites and Dr Google alone for now.

My question is- what genetic test needs to be done here? Does a general screen for 'NF' pick up all there is to pick up? Type, variants etc?

Also have an appointment at an Optometrist to check for.... I don't know? The Dr said NF causes 'changes' to the eyes and he could see any on the surface and I should get his eyes checked.

Thank you and my apologies for rambling. I've not slept much and am struggling with 'the fear'. Any replies appreciated.

People with NF sometimes have Lisch nodules on the surface of the iris -basically little lumps. They're used to aid diagnosis and are benign, they don't cause visual problems.

I'm afraid that's where my knowledge ends. Hope it all turns out well.

Thanks for your reply underneaththeash. I managed to contact an NF support group in Oz. Nerve wracking times!

Hi I just came on here to ask about this my ds has been under dermatology and genetics for a couple of years they’re thinking nf1 but also other things he had a skin biopsy today which was awful much more dramatic then anticipating and needed to be stitched they’re saying whatever it is now they’re not happy and it’s definitely something where as before they where saying maybe nothing I’ve been told to be very careful in the sun full swim suits and factor 50 and will take 6 months for results but we will be followed many times while we wait would love for anyone who’s further along in this process or has been through tho?

This is what we had done today

A young cousin of mine has NF type 1 the mild version. We are not super close but it seems to cause him to have mild learning difficulties and a few behaviour problems but other than that he seems to be healthy, happy and doing quite well, he is coping ok in his mainstream school.

My daughter has nf1 , and was diagnosed accidentally. She had a lump the size of a Marie fat pea that was fixed an her back and very sure when she did forward rolls in her gymnastics class. The Gp referred her to a surgeon and they agreed to remove it as it was fixed in place and clearly not gristle. We didn't think anything about it. We got called back a month later saying that basically they had sent it off to histology and the cellar structure and it being "spindly" and Column like was very unusual and was indicative of an nf nerve tumour/growth.... exotically as they struggled to remove it and it was painful. They checked her, said she has 3 cafe au lai spots and just to be aware of any new spots or lumps coming up. That was when she was 8. She's now 23 and hasn't had any other nerve lumps. She has had some very very large "mice" in her breasts that has to be removed as they were painful and the size of lemons. But she has recently been able to breast feed so the surgery didn't affect that. Pregnancy really bright out a few more care au lait spots but I've no idea if they will fade or not.

She does have some minor learning difficulties. But it's very hard to tell whether that is nf1 ( although her three siblings are all much higher achieving) .

Thanks for the reply’s very interesting my ds is 6 now he has many cafe au lait marks he was born with maybe 3 but many more have come up over bc the years he’s also starting to have some dark pigmentation around the eyes it was a consultant about a completely separate condition who kept counting his cafe au lait marks from a baby otherwise I wouldn’t have paid much attention as my side of the family all have a couple. He has no learning disability or neurological problems so I guess that’s a positive. Couldn’t believe I came on to start a thread on this and someone allready had.

@Hm2020 I am very sorry the biopsy was so traumatic.

In genetic syndromes with skin manifestations it is sometimes the only possible way to make a diagnosis . Some genetic mutations such as segmental (also called mosaic) NF1 occur at a post zygotic stage, which means not from the first cell, but shortly after in the first two days since conception, and in this case, depending where the mutation happened, a blood test might now show it because the blood cells were not affected. Taking a biopsy of the visible manifestation such as a piece of a cafe au lait macule is the best way to know for sure. Usually two samples minimum are needed and since they must be quite big 4-6 mm , a couple of stitches are also usually needed. I am sorry you weren't warned before.
Skin biopsies take longer to diagnose, but not months-longer. Usually a couple more weeks because fibroblast cells need to be cultured. So the six months frame was probably a worse case scenario time frame.
In the meanwhile, your DS will be under supervision and there might be a couple more tests / imaging coming. The most worrisome symptoms was probably the dark pigmentation around the eyes, also known as raccoon eyes so well spotted on the consultant.
Maybe it is just a tiredness thing or an allergy causing a very congested nose and they might go away.

In any case you are in good hands now.

Interesting you say it’s possibly the eye thing as dermatology and genetics have been taking pictures of the marks for 2 years but never called for anything more then bloods possibly because of the eyes that now they’re investigating he’s been put in some kind of study as they’ve said his presentation is extremely rare im hoping we’ll no more in a few months amazed to get so many responses as information on line seems very thin on the ground so thanks you everyone especially op for starting this please any others with experience I would love to hear.

The reason we, with genetic syndromes, have a deep knowledge is actually quite frustrating, and we don't study or learn about our disease because we want to, but because we have to.

The first thing we are told is to be smart and our own advocate, that we have to educate our doctor and that in the horse/zebra analogy (When you hear hooves, think horse, not zebra ) , we are the zebra and have to push for deeper investigation.
The scarcity of updated information you have noticed is the same information your physician will have seen or looked up. When it is not plain wrong, it is sadly 10 or 20 years behind, like in the case of the OP or yours to wait and see for the Cafe au lait macule. But wait for what? 40 years ago the genetic test didn't exist and the only way was to wait for symptoms to slowly add up over the course of years. Now we have the genetic test and it is even relatively cheap, a couple hundreds bucks, it will save 8 years in the diagnostic process.

The USA are far more proactive in that sense. Any newborn with cafe au lait will get the genetic test. UK and Australia are very resistant.

Genodermatoses syndromes - genetic diseases with skin involvement - are tremendously underfunded. The Australian government just announced with a fanfare 8 millions $ for Nf1 for both research and the CTF foundation over the next 4 years an. It is ridiculously low for medical research , more a slap in the face and a way of getting rid of us. You got your money , shut up now . UK and Australia wait for their local research to show the same results as what USA, Scandinavia or France 's research has shown. So not only is it a waste of years (decades) but also a waste of money which will be used to repeat clinical trials locally.

So whatever the outcome of your testing, if it is positive for any given disorder, you have to dig deeper and hit pubmed, and other current medical knowledge. Look at other countries guidelines, current clinical trials to see what the research is looking at, attend the yearly conferences and medical symposium, read, read and act.

Another UK/Oz characteristic is the patronising tone and attitude many specialists have. It might be a cultural thing but I'd rather have bluntness than underplay.

Thankyou so much for such a detailed reply I know very much about the horse/zebra analogy as my ds actually has a primary immunodeficiency which is why the cafe au lait marks have always been an after thought very interesting about the USA I had no idea.

Sorry to disappear! And thanks for all the replies- it seems such abroad and varied disease.

DS4 had a blood test last week to check for NF1 and Fragile X (even worse!) am trying not to think much further until I know what we're dealing with.

Apparently the appearance of lisch nodules on the eyes isn't necessarily definitve for NF, in that if he doesn't have any it does not mean he doesn't have NF. So decided to go straight for the decisive gene test.

Quite scary.