Long shot, but does anyone here have a child with Neurofibromatosis?

[Dustyblue]

Hello all, asking from Australia.

DS5 was diagnosed last year (via genetic screen and paed neurologist) with NF1. The assessment process is very long. We're waiting on more genetic assays to be done for us parents and DS again, plus a learning assessment. He's seen a paed opthamologist, and no optic gliomas were detected, so that's good.

Meanwhile, he's been seeing an OT, a Physio and a Podiatrist about his various issues. He starts primary school in Feb; I won't detail all my fears about that.

There are support groups online, but the main ones I've found have been run by people who have NF themselves. Now, there's a wealth of info there, but also lots of unhelpful things such as:

• I didn't know I had NF until I was 44, when surgeons spent 12 hours removing a tumour wrapped around my heart (Cheers, taa for that)

• I have NF but my children don't, you need to stick to the following diet plan to stop him developing tumours (Ahem, ok)

I'm a tad worn down with it all. Any experience here at all?

Thanks in advance

When it comes to NF you can't shut me up. I am associated with a international NF2 genetics forum where I provide expert information. In my personal E-library I have over 85,000 pages of information which I am quite happy to share at no cost. Let me know what you require & I'll post it for you

NF1 is mapped on the 17th. Chromosome.
Where NF2 is mapped on the 22nd. Chromosome.
Cafe au lait macules are generally used as a visual Diagnostic tool in NF1 & are less common in NF2 as are lisch nodules. In saying this there are over 100 conditions which display C.a.L's as a Diagnostic tool & some 60 conditions which display lisch nodules.
All types of NF have two types of manifestations the first being familial that is where a mother or father has the condition & has genetically passed the defective gene onto the child. The second type is called a Denovo {spontaneous} occurrence where the gene defects during foetus development. In all cases there is a 50% chance that 50% of children may inherit NF from a parent. NF CANNOT SKIP GENERATIONS. There are facebook support groups based in Melbourne & the Australian CTF. is quite good & has information which can be provided via their website.
NF has no particular ratio in either gender, in saying this there have been extensive studies into the effects of menstrual cycles & pregnancy has on NF due to hormone release.

Do you mean REINS @TonywithNF2 ? I am in a few groups myself 🤓. I was asking about you tutoring senior medical students. I imagine the neurofibromatoses get only a few lines in textbooks unless you are doing a specialty .
I am very curious about the 60 conditions having Lisch nodules as clinical manifestations. Could you share the link please. Thanks for offering to share your library.

You are right that there is no difference in incidence at birth for NF1, however, the disease is more deleterious to women and we have a greater life expectancy reduction compared to men, mainly because of increased malignancy. Is it the same for NF2?

The extensive studies about pregnancy you mention came to the conclusion that pregnancy doesn't accelerate CN progression. The passing of time does. In fact, we do get worse at menopause, when hormone level plummet. We are after all a disease of ageing. We have all the old folks diseases. Osteoporosis, dementia, cancer, ... and preventative measures can and should be taken as early as possible. I find fascinating how dietary protein restriction can normalise our altered bone cell formation, or how limiting dietary fat can rescue our lipid storage myopathy. Given both NF1 and NF2 are cell cycle regulators, I would think, inhibiting mTOR by protein restriction would be beneficial for NF2 as well. Are there any studies on nutrient manipulation in NF2 I don't research NF2, but accidentally I will, from time to time, find a study mentioning compounds. What is your take on Sulforaphane for preventing VS in NF2?

@Dustyblue the diagnostic process didn't catch up with the current knowledge of Nf1, and it still causes distress by its lengthy time and unnecessary diagnosis delay. I am sorry about that.
When it comes to behaviour and deficit, I wanted to put a warning about the Golem effect. I would suggest you spend some time reading about the Golem and its opposite, the Pygmalion effect. At a medical conference, I assisted to a heated debate between a neurologist and a psychologist, on how the emphasis on difficulties was causing an increase of difficulties. Food for thoughts.

As per your request here is a brief list of articles on the effects of pregnancy with Neurofibromatosis.

The effects of pregnancy on growth dynamics of nerofibromas in neurofibromatosis type 1
Pubmed.ncbi.nlm.gov
☆
The effects of pregnancy on growth dynamics of nerofibromas in neurofibromatosis type 1
Journals.plos.org
☆
Neurofibromatosis type 1: pregnancy complications a population study
agor.org
☆
Neurofibromatosis in pregnancy
library.wmuhnhs.
☆
Eruptive neurofibromas in pregnancy - JAAD case report
jadcasereports.org
☆
Neurofibromatosis type 1 & pregnancy complications: a population based study | report PDF
researchgate.com
☆
Neurofibromatosis: effects of pregnancy on the skin manifestation
jamanetwork.com.
☆
Neurofibromatosis & HIV in a pregnant woman
facts.com

Following is a list of conditions which display Lisch nodules.
Busaccas nodules
Chordial nevi
Chordal nodules
Cogan reccece syndrome
Congenital ectropion uvae
Dendrites melanocytic
Down syndrome
Granulomatous melanocytic
Granulomatous uveitis
Inflammatory nodules
Iris atrophies
Iris cysts
Iris mammillations
Iris melanoma
Iris neovascularization
Irido-corneo-Endothelial syndrome
Juvenile Xanthorgranuloma
Kopp's nodules
Legius syndrome
Leiomyoma syndrome
Lepra syndrome
Mast cell syndrome
Melanoma
Multiple iris nevi
Myelinated nerve fibres
Nejm-lisch nodules
Neovascular glaucoma
Optic nerve Gliomas
Pulsating exophthalmos
Rieger’s anomaly
Retinoblastoma
Scarcoidosis
Watson's syndrome
Xanthogranulona {adults}

The following conditions all have associated cafe au lait macules.
Albright’s-Russell
Ashydermantosis
Ataxia Telangiectasia
Autoimmune haemolytic anemia
Banayan-Riely-Ruvalclba
Basal cell nervus
Becker's melanosis
Behcet’s
Benign congenital nevus
Blashchkoliner fine hyperpigmentation
Blashchkoliner whorled hyperpigmentation
Bloom.
Carcinoid pigmentosa
Chaucer’s
Chediak-Higashi
Cobb
Coffin Siris {MIM135900}
Congenital Melanocytic nervus
Congenital Melanocytic skin lesions
Constitutional mismatch repair deficiency
Devoid basal cell carcinoma
Divry-Van Boegart
Dyskeratosis Congenita
Early nevus spilus
Epidermal nervus
Familial cafe au lait macules
Fanconi anemia
Gremline de novo
Griscelli.
Hashimoto's thyroid
Hereditary haemorrhagic Telangiectasia
Hunters
Hypomelanotic cutaneous macules
Hypothesized RASopathises
Incontientia pigmenti
Incontenientia pigmenti achromians
Jaffe-campanacci
Johanson-Blizzard
Juvenile idiopathic Epilepsy
Kabuki syndrome
Legius
Lentigo
LEOPARD
Linear sebaceous naevus Jadassoha
Lumbar lipomeningomyelocele
Manfucci
Mastocytoma
Meckel-Gurber
Melanocytic nervus
MEN1
MEN2
Microcephalic osteodysplastic
Mongolian spots
Muscosal neuroma
Multiple endocrine neoplastia type 2
Multiple mucosal neuromas
Neonatal period FEMALE ONLY
Neuro-cardio-facial-cutaneous
Nigimegan breakage
NF Type 6
Nervus spills
Nigimegan Breakage
Noonan type 1
Noonan with multiple legtigine
Occult spinal dysraphisim
Parkinson’s WITH vitilgo
Paediatric Wiskott-Adrich
Peutz-Jeghers
Piebaldism
Pigmentated lichen planus
Reticulate hyperpigmentation’s
Ring chromosome {1~11~12~13~17}
Rubinstein-Taybi
Ruvaleaba
Segmental pigmentation disorder
Silver-Russell
Speckled lentiginous Nervus
Sporadic cafe au lait
Sturge-Weber
Tiberous sclerosis
Turner
Urticaria pigmentation
Vitilgo
Von Hipple-Lindau
Wagemann-Frobese
Watson's-Adrich
Xeroderma Pigmenntosum
Xeroderma pigmentosa.

As per your request here is a brief list of articles on the effects of pregnancy with Neurofibromatosis. I haven't asked for any of these

Following is a list of conditions which display Lisch nodules. This is incorrect. It is just an extract of a database that includes a mix- and -match of differential diagnosis ( Busacca nodules for example), associated manifestations (optic glioma) , medical papers (NEJM-Lisch nodules stands for New England Journal of Medicine) and so on.
The fact that Lisch nodules are mentioned in a paper that talks about a boy having both Down Syndromes and NF1 doesn't mean, Lisch nodules are a clinical manifestations of Down syndrome. We can have Nf1 and many conditions at the same time.

The following conditions all have associated cafe au lait macules. Again , I haven't asked for any of these. And again, it contains the most random content, such as "NF type 6" , seriously, we are talking about prehistoric stuff in the early 1980s , when NF was still a mystery and for a while they attempted to classify the manifestations into types. We would have more than 25 types today if we were still following this line of thought!

My DS (8) has seven cafe au lait marks, that have appeared gradually since birth. They are monitoring him for NF1, so six monthly eye checks for nodules, so far none found. He also has a brain injury from birth (unrelated) so only delays is mild physical disability due to that. Lots of people in my family have the birthmarks and no other systems. I declined genetic testing.

@Peanutlicious before the age of 10, Lisch nodules are only seen in 50% of children. It is one of the late-onset manifestations and therefor the absence of Lisch nodules in childhood is not a valuable diagnostic criteria.

This said, CALs are very common in children, and even multiple CALs in older children without NF1.

Can I ask why you declined genetic testing? If he doesn't have it, it is something you can erase from your mind, and if he has it, you can start acting to avoid severe manifestations and the earlier you start, the better.

Dustyblue, just read that your child runs hot & sweaty. Dose this mainly occur at night & the sheets are soaked in perspiration? If so has your child been assessed for a Pheochronocytoma on the adrenal glands attached to the kidney/s. These tumours effect the function of the heart & must be taken seriously. Respectfully I would suggest a referral to a Endocrinologist

Thanks @TonywithNF2 No, he doesn't soak anything with perspiration. We've just noticed that he often feels hotter than us, isn't fussed about warm clothes when it's cold and sometimes feels sweaty. We'll be seeing the NF clinic at RCH soon I hope, so I'll bring it up with them.

I'd be interested in some beginner reading if you could suggest some, it's clearly a highly complex condition and I need to work my way through from the basics.

@Kaiken Yes I'm aware of the Golem/Pygmalion effects. Certainly very plausible. I'm finding the behavioural/school issues hard to navigate.

OK for those of you who have asked about my time tutoring medical students. Like all good storytelling it started off last century. In 1964 to be precise when I was born clearly displaying NF.

Most my life I had been a lab rat of sorts without even knowing it. The doctors would rave on about NF & I would think these guys are a bunch of dickheads.

I use to sneak into the medical school library & the books were just as bad, only a paragraph here or there or some wanker wrote harmless skin condition.

It wasn't until 1990 when I was invited to take part in the senior medical students training programs at Flinders Medical Hospital here in Adelaide. Genuine interest was shown in what I had to say & about my experiences.

I was asked serious medical question about our NF in a medical capacity, I was stunned without realising it the information flowed freely, my terminology needed improving a lot but that came with time & exposure.

Every time I was in hospital medical would scurry over from the attached medical school to see me & ask questions {The amount of times I helped with assignments}

Herald the arrival of the internet & dedicated scientific NF groups & the explosion in the exchange of knowledge not just with fellow NFer's but with dedicated genetic experts who freely shared knowledge.

Now days I am regulated to a few support groups & proof reading the occasional PhD neurofibromatosis submissions & spending my time as a expert in a specialised NF2 science forum.

Within my E-library I have several hundred publications on Genetics & manuals solely dealing with Neurofibromatosis & of course I can share copies of these.
I am uncertain if the moderators of this site will permit a book of 300 pages being posted here.

Those who would like such books please email me at [email protected]

Our national support agency is the children's tumour foundation BUT ONLY Australian members allowed. In saying this there information is quite good along with educational material for children fortunately I can download there material & handball it anywhere in the world. What are you looking for?

I appreciate your offer. Have found it difficult to source specific info without becoming overwhelmed. This is still a new and emotive issue for me.

I guess I should start with the genetics of NF1. I've done some study in genetics as part of a (non-clinical) masters degree, so hopefully I'll be able to wade through the detail.

Then, something around management & preventative strategy for kids (DS just turned 6).

Is the CTF on Facebook? I don't do Facebook.

I will email you, thanks

There is an event in Victoria this Saturday www.ctf.org.au/events/31/infoday
Either in person or zoom, it will be a way to get started on your learning about NF1 journey.
I find the resources on the webinar section of the NF Network quite useful.
www.nfnetwork.org/resources/webinars/ For the management of Nf1, this one might be useful.

There is very little literature in terms of books when it comes to NF1, compared to other genetic disorder or neurological syndromes. The last one was published in 2020, then the one before 2013, and so on with similar gaps. None was written for parents or patients with the exception of a very old Handbook from the 1980s, republished in 2005, but the knowledge acquired since 2005 has been not only abyssal, but game changing as well making that handbook obsolete.
Pubmed is where you will see the trends and breakthrough in research. You need to understand how research works, how poorly funded it is, how redundant and repetitive it is,.
There are medical symposiums and conference all year long. Some, such as the CTF conference are well advertised, others less so. There are working groups, forums and experts panels that meet up on zoom regularly, exchanging ideas and defining criteria and domains for research.

To act preventatively, you need to understand what NF1 is, a protein that regulated the cell cycle. When mutated the cell cycle is accelerated and the metabolism is altered in many way. We have

• an abnormal lipid metabolism which means not only that we store dietary fat in muscle but also that when we need energy, we are not efficient at converting fat into energy and as a result we get more tired,
• an abnormal glucose metabolism, with in particular a brain glucose hypometabolism which is exacerbated by high fat diets
• our bone cell turnover is too fast and this mean we have poor quality bones resulting in early onset scoliosis and osteopenia (48% of us)
• we have an accelerated immune system, resulting in high levels of mast cells that alters our circadian rhythm and sleep patterns. We have high inflammation because of our altered immune system and inflammation is needed for tumorigenesis.
• the increased metabolism also results in higher oxidation.

This chapter summarises some of the metabolic features www.intechopen.com/chapters/77253 you will need to create a free account to download it.

@Kaiken That is brilliant information, thank you so much.

I will absolutely zoom that session, how well timed!

It's dinner time here so can't reply properly. But thank you, I truly appreciate having good starting points like this.

In an ideal world, a finding of a research trial would be converted straight away in a change in protocol In the reality , it takes 15-20 years. We have known since 2001 that MEK inhibitors work in reducing plexiform neurofibroma, one of our most terrible manifestations, yet it took 19 years for the drug to be approved and listed.

We know we are not good at processing fat, that we store dietary fats in muscle instead of fat cell. Fat intake will also alter dopamine and GABA and increase likelihood of behaviour disorder. We have papers on that. We know high fat diets alters NF1 gene expression. We already have less neurofibromin circulating.
We have graphs that show that a low fat diet increases force, and now would think that a protocol recommending a low fat diet would be implemented, In the same way, trials in rat shows that restricting dietary proteins will normalise our osteoblast and osteoclast turnover which is too fast. Again, it would make sense to recommend a low protein diet, but nope, again nothing. Those studies aren’t even repeated. There is information which lies forgotten in pubmed since 2006...

Diet is complicated because it takes resources that are not there. It is easy to prescribe a pill. But a dietary program requites follow up, encouragement, dietician, plans, …. Italy does it . The NF1 centre in Naples offer dietary consultations.

Human trials are expensive, take time and it is difficult to find participants you can trust will comply for six months, eating what you tell them to eat and avoiding the forbidden food. Can you imagine a trial in Australia telling participants to drop bacon, burgers, sausages, fish and chips, all fried food, processed food, red meat, processed meats ? For six months?
So they don’t do it. One has been done in 2017 in Italy. Showed success with a Mediterranean high polyphenols diet. Nobody has even tried to repeat it. It is very hard to find participants for trials. They imply a cost for participants. I have to pay transport/petrol and hospital parking fees which are expensive. I have to take time off work.

What I am trying to say, it that there is the science you will find and read, and then you need to understand how the science is done, funded, how a researcher’s career is linked to them being published and therefor how everybody takes the safe route of a trial that won’t be rejected (MEKi, everyone and their dog are doing it, in every continent, wasting millions, since it is the same research repeated again and again). Prepare a diet trial, very high chance of fund refusal. Because you can’t pinpoint a component, a compound, a cellular pathway, because the human body doesn’ work like that. Food works in synergy with the metabolism, the microbiome, ...

The NF1gene doesn't cause tumour. A mutation on the gene means less neurofibromin is circulating and the brakes are off in the cell cycle. IT is go go go. Cell growth, proliferation, turnover... No cellular pathway is simple. There are many players upon which we can act.

All catagories of NF I tutored all types & Associated complications ranging from idiopathic manifestation, Precocious puberty, academic concerns basically anything there was.
For 58 years a life of NF is all I've ever known, I don't know anything different.

My research E-library is extremely complex & more than happy to share any information. Keeping in mind I had to reduce its contents to 85,000 pages.
There are some good children's story books & comic books called Moxie & sparks & others which help explain NF to children. There's also downloadable colouring in books.

A database has the risk of becoming outdated quite quickly .

Information changes. What was true yesterday is proven wrong today.
We have seen it with the belief that pregnancy would exacerbate neurofibroma eruption. No longer true. Or the affirmation in the old books that neurofibromas don’t go away, once you have them. Not true again.
New information is also added . In none of the papers prior to 2021 is dementia mentioned. We have now established that we have an
increased risk of dementia and especially Alzheimer disease. Just a year ago, that piece of information didn’t exist .

I think it would far more beneficial for you to create your own library based on what is meaningful to your child and current knowledge. Start here.

CTF Australia has a very poor resource library, but CTF Global/Europe has a great library. So does NF Network , NF Midwest

ctfeurope.org/understanding-nf/tools-for-kids#comics specific for kids
ctfeurope.org/resources/resource-library
www.nfnetwork.org/resources/educational-materials/
www.nfmidwest.org/learn-about-nf/be-informed-database/

You won’t miss anything by not being on FB. Many groups are open, and you can read a lot of misinformation

Universities involved in research do post on their media page from time tot time such as mediaspace.umn.edu/playlist/dedicated/1_9g0gz1vz/1_90u32anj

And if you like conferences, make sure to enrol in the INFER series , masterclasses on specific topics to which you can assist live and have the option to ask questions or just wait for the recording to be posted. Here you can read info and see the old recordings www.ctf.org/research/masterclasses-in-nf . Earlier this year, there was one on the paediatric management of NF1

I understand it might seem daunting, but in no time you will be munching on medical jargon for breakfast. We are a rare disease. We have to be the ones with the knowledge, because a lot of researchers move on . They do NF1 for a bit, then they are gone , they move to other specialties or other countries and with them gone is their knowledge and the next time you are at the hospital, the registrar you see will be someone doing a six month rotation in genetics who knows a massive nothing about NF1. The onus is on us. You will be the one educating your GP.

We are not MS, or cancer, or other disease with huge funding. We have crumbs. It is slightly better for children but the care disintegrates as adults if you are not proactive.

The information exists, It is there for us to read and use. Australia still has the mindset “ wait for a problem to occur and then we will deal with it” . I am not wanting for a fracture to tackle my lowish bone density, especially given the treatments for the general population do not work for us given the cause of our bone defect is different. Medicare doesn’t cover for my bone scans, or the physio sessions I had to design a program I now do alone. And in the same way, I am not waiting for signs of cognitive decline to adopt preventative measures for dementia . Once the bone or the mind is gone, it is gone forever.

I'll try to post some of the books in my collection directly to this site, many are well over 100 pages each & are professional handbooks, others are guidebooks for parents on NF1. there's also reference material for schools & educators, I'll complie a list to see what everyone wants, more than happy to hand it all around.

That would be great, thanks

As for not choosing left or right that will kick in let them work it out for myself I am ambidextrous probably a trait from my father along with NF.
As for schooling there's good reference material available for schools to support children in their educational challenges. I'll jump into my E-library & compile a list of booklets which are available. For parents, teachers & students

As promised eyes a basic run down of articles & literature for children & educators that's scattered in my E-Library.

Comic books:
-9pg. Archie jumbo comics children's tumour foundation.
11pg. Biobank questions & answers.
12pg. Sophie's science project what is medical research?
24pg. The NF Hero.

COLOURING IN BOOKS:
28pg. John Hopkins guide to surgery.
-6pg. Understanding surgery.
32pg. A child's guide to surgery.
29pg. My trip to hospital -colouring in book.
24pg. A read a-long colouring in book about surgery.
20pg. Welcome to UC DAVIS children's hospital.
32pg. My thinking cap A colouring in book about epilepsy.
16pg. Colour jam with Maxie & Sparx

STORY BOOKS:
52pg. Katie's finds her courage, a book for children with NF1.
-6pg. Polly's best friend
-6pg. The winning goal.

EDUCATORS:
A guide for teachers NF1
Supporting a student who has NF2.

There's heaps more just have to collect them into one dedicated file

I am attempting to reduce my Genetics / Neurofibromatosis E-library by 15,000 pages. Are there any subjects people are looking for before I start dumping?

Tony
hi I had a brain tumour removed 10 years ago . All along it was an acoustic neuroma
a few years down the line they said it was a neufibroma. Something so serious you would think they would get the terminology right.
have you any information about this.

iv had a terrible two weeks as there been a burglary in the family. So I have only skimmed through your posts. I really don’t understand 1 and 2.
I think they said mine was just one on its own. Which category will this come under.
I have to have scans every five years. The tumour was large. Thank you

Would you like a copy of microsurgery techniques in vestibular schwannoma surgery I have other documentation which I can e-mail