Need some expert help with a genetic neuropathy
 

Hi All,

I need some help from one of you experts out there.

I have NLD SFN confirmed by skin biopsy showing increased nerve fibers. I am 38 and my sister is 35. She has been backwards and forwards to neurology over the last 3 years with complaints saying she has very hot feelings on her skin. She says these are not painful. They are not similar to my symptoms.

She has seen about 4 different neurologists and they have all said she is fine (one of them is my neuro). However, the last one, due to the fact I have confirmed SFN, has referred her to the Professor in London who carries out the skin biopsies here in the UK.

The neurologist she has just seen has told her that it is pointless going to get the biopsy done as there is nothing they can do about it as it will be hereditary.

Can anybody explain to me how this can be correct? My mother and father have never had any such issues or SFN? I know you can have a genetic mutation that can happen , but surely it wouldn't have happened in both of us both at the same time? Is this possible?

My sister is a hypochondriac, so not sure if this is part of it, but these 'hot' feelings she talks about on and off, she doesn't say it is like sunburn, just like her back has been on a radiator and gets very hot.

Is this more likely to be some sort of toxic exposure that we would both have had a genetic susceptibility too? It just doesn't make sense that we could both have it, both at the same time, if our parents or nobody in our family has?

I'm now very annoyed with her neuro , as it is extremely distressing to think it could be possibly passed onto my children.

I would be really grateful if anybody has any knowledge of genetics could explain and hopefully put my mind at rest?

Thanks

Loulou

LouLou, I am puzzled by what you have been told.

In general, genes which are strongly associated with a disease come in two classes.

In one class the mutant gene encodes a protein which has gained an abnormal (pathological) function. These diseases are very rare and show a strong familial pattern - a child of a parent with one of these diseases has a 50% chance of inheriting the mutant gene and so will get the disease. This does not seem to apply to you and your sister.

In the other class the mutant gene encodes a protein which has lost its normal function. Somebody with one copy of the mutant gene and one normal copy will be fine because the normal gene copy ensures that they have the normal form of the protein. People like that are "carriers" of the disease. These diseases are relatively common.

Cystic fibrosis is an example - somebody may develop it if both of their parents are carriers. Cystic fibrosis occurs when somebody inherits the mutant form of the gene from both of their parents - there is a 25% chance of this happening.

Hi LouLou

If you search: "Hereditary sensory and autonomic neuropathy" there is a Wikipedia page with some info that may be of use.

I also came across this site which helps explain how genetic variations can occur or be passed down.

What are the different ways in which a genetic condition can be inherited? - Genetics Home Reference

Hope you can get some explanation of the genetic connection.

So if both my parents were carriers and had had two children that both developed the disease is this possible? I mean if we were both the unlucky 25percent? Kiwi do you think it is more likely that this is due to some sort of exposure? Her neuro is rubbish. I can't believe he said it is pointless to get the biopsy. However he agreed to let her have it. Do you think it would be possible to pass on to my children? Thanks for your help kiwi

Thank you bluesfan that is very helpful information.

LouLou, I think that the link from bluesfan is excellent - it is well worth a read.

Geneticists use the word "penetrance" to explain how likely it is that inheriting a particular form (an "allele") of a gene leads to a health problem. In the single-gene diseases that I mentioned above, penetrance is often high (close to 100%) but these diseases are very much the exception, not the rule.

In most diseases inheriting alleles of many different genes are usually risk factors. This is very complicated; for disease X inheriting allele 23 of gene A might be a negative risk factor. This might be made worse in somebody who has inherited allele 45 of gene B but better if they have inherited allele 14 of gene C, and so on.

I don't know any examples in which sorting out these complicated patterns has led to improved therapy/treatment but this could change.

Now, cutting to the chase for you and your sister (all that I am concerned about here), you wrote:

"The neurologist she has just seen has told her that it is pointless going to get the biopsy done as there is nothing they can do about it as it will be hereditary."

Bluntly, this is nonsense. The neurologist may or may not be a good clinician but s/he knows slightly less than nothing about genetics.

It is what is called genetic determinism - "OMG, it is in my genes. There is nothing that I can do. I am doomed.". With the rare exceptions of single gene diseases, genetic determinism is a total myth.

One-line summary; if you (with confirmed SFN) or your sister (with possible SFN) decide to have children then go for it. Your genetics (and those of your partners of course) mean that your children are unlikely to be at greater risk of SFN than any other children.

Thank you so much Kiwi, that does make sense. I had been offered IVIG, I have a really good neuro who thought mine is immune mediated or a sub type of Guillian barre. My sister spent 5 minutes with that neuro, who I believe just fobbed her off saying " well we can't do anything for SFN, we can give you the pain meds now, you don't need to bother having the biopsy as if it comes back positive its hereditary so there's nothing we can do" . I have two small children and my sister has a daughter, so we were both left a bit worried after . Thank you to both and Blusfan, good job there are people like you on this site

Do you live in the same house?

Hi health girl. We don't but my sister spends a huge amount of time here. Our symptoms both started in December 2012 . It seems a big coincidence if it's genetic? Hope you are getting some answers for you and your family. When I see my neuro will explain what's been going on. I'm very surprised that my sister's neuro told her not to have the biopsy as if it sfn then it's genetic . I would expect a good neuro to look into this further it is awful.

Well if there is no treatment to cure it, I guess you would be the one they would pick apart. From what I'm learning, those of us who are predisposed, all it takes is a trigger from an exposure to flip on the gene that can cause symptoms like these. I will keep everyone posted when I get back from the geneticist next month.


Sent from my iPhone using Tapatalk