19 year old niece on respirator with Miller Fisher Syndrome

[ChapelHillSooner]

This is a variant of Guillain Barre syndrome. It will be the fourth person in my family that has GBS or MFS. My grandmother and dad died of it. My uncle had it but recovered but died of COVID due to inability to get vaccinated.

There is supposedly no known genetic link to it but I did a back of napkin calculation because 1) I am a nerd and 2) the result is actually relevant:

The lifetime risk of getting GBS is 1/1000. MFS is more rare but I'll use GBS numbers in this. As a nerd I had to calculate the odds if in fact there is no genetic risk.

There are 22 blood related relatives from my grandmother (who died of GBS) down to the great grandchildren. So if I did the calculation right, that means the odds of it happening randomly is 22! / (18!*4!) / 1000^4. That is about one in 137 million.

Sounds like the prognosis for MFS is good - about 90% survival for people who need ventilation. On a more selfish note, I think I will really have to reevaluation whether I can be vaccinated. I think I will continue to do it but I have to think about it.

Edit: To be fair, I should calculate the odds of 4 or more but I don't think the odds are going to change. The odds wouldn't change much as it gets progressively smaller if you added the other terms. (If anyone - super - knows a shortcut to do the 4 or more calculation, let me know. I could write a program in five minutes...)

 

[nycfan]

First and foremost, sending good thoughts for your niece to recover.

But that is wild — has anyone raised it with a family physician how common it is in your family? Seems like that’s the kind of thing someone should study because it seems nearly impossible to believe there is no genetic component (or of everyone lives close to each other, an environmental one?) given the frequency.

 

[superrific]

Edit: To be fair, I should calculate the odds of 4 or more but I don't think the odds are going to change. The odds wouldn't change much as it gets progressively smaller if you added the other terms. (If anyone - super - knows a shortcut to do the 4 or more calculation, let me know. I could write a program in five minutes...)

You want the cumulative binomial formula.

 

[nycfan]

“… Familial occurrence of GBS is rare, and only 42 patients from 20 families have been reported so far. Majority of them are from European countries. Familial occurrences do suggest the involvement of some as yet unidentified genetic susceptibility factors. …”

Familial Guillain-Barré syndrome: A case report with... : Neurology India

an countries. Familial occurrences do suggest the involvement of some as yet unidentified genetic susceptibility factors. We report the clinical and detailed electrophysiological findings of three affected brothers from Arunachal Pradesh who presented with possible familial GBS....

journals.lww.com

So maybe there is some rare familial susceptibility in very rare instances …

 

[ChapelHillSooner]

I had ho

First and foremost, sending good thoughts for your niece to recover.

But that is wild — has anyone raised it with a family physician how common it is in your family? Seems like that’s the kind of thing someone should study because it seems nearly impossible to believe there is no genetic component (or of everyone lives close to each other, an environmental one?) given the frequency.

They don't rule out that there could be a genetic component but just say that there isn't strong evidence for it.

After my dad died, I mentioned it to my physician but he didn't really have anything to add. I guess I wouldn't expect him to.

I really hoped that there might have been a shared environmental risk factor but my niece getting it kind of rules that out as she wouldn't have shared any of the same environment as the others.

 

[superrific]

“… Familial occurrence of GBS is rare, and only 42 patients from 20 families have been reported so far. Majority of them are from European countries. Familial occurrences do suggest the involvement of some as yet unidentified genetic susceptibility factors. …”

Familial Guillain-Barré syndrome: A case report with... : Neurology India

an countries. Familial occurrences do suggest the involvement of some as yet unidentified genetic susceptibility factors. We report the clinical and detailed electrophysiological findings of three affected brothers from Arunachal Pradesh who presented with possible familial GBS....

journals.lww.com

So maybe there is some rare familial susceptibility in very rare instances …

The whole thing is very rare, so I'm going with "there is some familial susceptibility"

 

[superrific]

But that is wild — has anyone raised it with a family physician how common it is in your family? Seems like that’s the kind of thing someone should study because it seems nearly impossible to believe there is no genetic component (or of everyone lives close to each other, an environmental one?) given the frequency.

This is the problem with very rare diseases. They don't get much study, because of a few factors:

1. No money for treating a problem that affects 100 people annually
2. A shortage of patients who can be studied.
3. It's basically impossible to develop any pharma products for such a small population.

I'm guessing your husband knows far more about these issues than I do.

 

[superrific]

I had ho

They don't rule out that there could be a genetic component but just say that there isn't strong evidence for it.

After my dad died, I mentioned it to my physician but he didn't really have anything to add. I guess I wouldn't expect him to.

I really hoped that there might have been a shared environmental risk factor but my niece getting it kind of rules that out as she wouldn't have shared any of the same environment as the others.

ChatGPT says that vaccinations aren't a cause, that the syndrome follows infections. What ChatGPT knows about this is unclear. What scientists know is also unclear, given its rarity.

Hopefully everything will turn out OK for you. Between you and Rock, our community is getting rocked by chronic illness

 

[dcf2]

Some lit on familial Guillain Barr Syndrome - but not much.

https://www.sciencedirect.com/science/article/pii/S0165572821001788?via%3Dihub

Abstract​

Guillain-Barré syndrome (GBS) is an autoimmune disease in which the peripheral nerves are affected. GBS has different subtypes, such as acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). Infections, e.g. Campylobacter jejuni, influenza, etc., can lead to GBS. Both environmental and genetic factors play a major role in the occurrence of GBS. Several studies have investigated the genetic basis of GBS. Human leukocyte antigens (HLA) genes, Cluster of Differentiation (CD) 1A, FAS, Fc gamma receptors (FcGR), Intercellular adhesion molecule-1 (ICAM1), different interleukins, Nucleotide oligomerization domain (NOD), Toll-like receptor 4 (TLR4), Tumor necrosis factor-α (TNF-α) are among the genes reported to be involved in susceptibility to the disease. Dysregulation and dysfunction of the mentioned gene products, even though their role in the pathogenesis of GBS is controversial, play a role in inflammatory pathways, regulation of immune cells and system, antigen presentation, axonal degeneration, apoptosis, and cross-reaction. This review aims to summarize associated genes with GBS to contribute to better understanding of GBS pathogenesis and discover the gene pathways that play role in GBS occurrence.

In that paper - Table 1 lists case reports of familial GBS - but few enough exist that they can all be listed in a table.

 

[boogeyman]

Common sense would say there is something genetic about it being that is so rare and has affected that many people in the same family. Probably just so rare there isn't much research on it to know.

 

[ChapelHillSooner]

You want the cumulative binomial formula.

I was looking at that and realized I left out the term that isn't going to change the results - .999^18.

 

[ChapelHillSooner]

“… Familial occurrence of GBS is rare, and only 42 patients from 20 families have been reported so far. Majority of them are from European countries. Familial occurrences do suggest the involvement of some as yet unidentified genetic susceptibility factors. …”

Familial Guillain-Barré syndrome: A case report with... : Neurology India

an countries. Familial occurrences do suggest the involvement of some as yet unidentified genetic susceptibility factors. We report the clinical and detailed electrophysiological findings of three affected brothers from Arunachal Pradesh who presented with possible familial GBS....

journals.lww.com

So maybe there is some rare familial susceptibility in very rare instances …

Make that 46 in 21 families.

Or if the great grandchild isn't close enough, 45 in 21 families.

 

[dcf2]

This is the problem with very rare diseases. They don't get much study, because of a few factors:

1. No money for treating a problem that affects 100 people annually
2. A shortage of patients who can be studied.
3. It's basically impossible to develop any pharma products for such a small population.

I'm guessing your husband knows far more about these issues than I do.

Yes to all of that - in addition it seems that candidate associated genes are not conserved in standard animal models (mice) making the barrier to animal modelling of mechanism much higher.