Genetic research for Chiari? Perhaps a possibility

General
1

Hello, I'm going to start this out with a disclaimer. I only have a bachelor's degree, and I am in no way, shape or form a medical professional. I'm just an overzealous journalist who has Chiari. Also, don't read this if your brain is foggy today. There's a lot of technical mumbo-jumbo.

A news story from the AP today caught my attention - it was about using genetic testing to diagnose children with neurological problems and adults who have strange symptoms. Sounds like it should be all about Chiari, right? It wasn't though, and it lead me on a hunt for gene research in Chiari.

I'm a giant nerd, and I had to share this with people who might care.

1. This interview caught my attention: Interview link

Basically, it's a genetic researcher who thinks it's possible that a test could be developed to check genetic structure for deficits that could indicate Chiari. Here's one reason why:

2. One possibility

This writer cites medical journals where researchers have found that genetic variances on chromosomes 9 & 14 could lead to hereditary Chiari-like symptoms, such as a decreased Posterior Fossa volume (AKA: No room for your brain in the back). Researchers took this information and found that the variances in a protein called fibrillin 1, or FBN1 may cause this.

3. Another government page indicates a FBN1 deficit may cause three genetic conditions which involve misshaped skulls.

Some of these genetic conditions involve Marfan syndrome, Weill-Marchesani syndrome, ectopia lentis, stiff skin syndrome, acromicric dysplasia, MASS syndrome, and Shprintzen-Goldberg syndrome.

According to the Marfan Foundation, related disorders include Loeys-Dietz syndrome, Ehlers-Danlos syndrome, and Familial Thoracic Aortic Aneurysm and Dissection.

4. There was a study done at John Hopkins in Pediatric Neurosurgery comparing autosomes in families that more than one member had Chiari. Researchers in the 70-80's found that traits could be dominant AND recessive, meaning that Chiari could possibly be hereditary? However, I believe there wasn't enough data collected back then for this to come to a meaningful conclusion.

5. My quandary is this: How likely is it that a genetic mutation in FBN1 could be to blame for all of these disorders, especially Chiari? What kind of research could be done on FBN1 to see this through, and is it being done already? Also, what could we as Chiarians do to aid researchers? Is there any way we can contribute our DNA for testing on this?

This testing website indicates that FBN1 testing is being done for Marfan's syndrome, but nothing for Ehlers-Danlos or Chiari. I wonder why this is. Does anyone happen to know? Perhaps this link has been already been discredited, and my evening's rampage of medical research is in vain?

Please, please, share your thoughts. I'm very interested in this.

2

Thanks, Abby! I'm going to take this post to other Chiari outlets and see if there's any one familiar with research that's going on. Does any one have any ideas?

3

Have you not checked the genetic research being done at Duke? I have recently been in email contact with the researcher and they have not identified a genetic marker for Chiari Malformations.The study started 2/1/10. US Clinical Trials have to be approved by a committee. Even if we all wanted to donate our DNA there is no guarantee we would find a researcher or they would ever get approval or funding to do the study. I work with & know a lot of researchers and NIH & DHH employees. It's very frustrating. NS & scientists are split over weather or not they think CM is genetic. I personally think it can be both. Mine is specifically not genetic in anyway. I will be interested to see others perspective, but in almost 4 years why hasn't Duke been able to prove a genetic marker if there is one?

http://www.clinicaltrials.gov/ct2/show/NCT01060800?term=chiari+malf...

4

Yes, if you have two or more people in your family with Chiari diagnosis and would like to participate, contact Dr. Gregory at Duke.

5

There are 4 members between 2 generations in my family with Chiari 1. I read somewhere that only 11% of the Chiari population are familial. I wish I could remember where I read that. Odd you mention Duke, becausemy nniece is being treated there…

6

I find this very interesting ad well. My daughter and I both have chiari and both went through the decompression surgery. We both still have a lot of symptoms. You also mentioned aneurysm and dissection which my father has. I have long questioned the genetic link. Have searched on the internet for information on this but it seems as though there is just not enough research to confirm it. I appreciate you sharing your research with us!

7

This was very interesting, thank you.

I don't think you are off -- at all. This is why.

I live in Maryland and I have Ehlers Danlos Syndrome (as does my daughter). I have seen Dr. Claire Francomano, Dr. Howard Levy and Dr. Fraser Henderson. Dr. H operated on myself and my daughter.

My former neighbor is a nurse; she and her daughter had Chiari & EDS.

She and I both spent a considerable amount of time with both Dr. Francomano and Dr. Henderson. At one point, Dr. H was in the ER with myself and my daughter for 5 hours (as in, he was there as a civilian, in the small ER room with us, advocating for us with the ER doc-- but that's a different story.)

This is my point: It has been the consensus by people who know Chiari very well (stated to me, informally, and I did not ask)-- that you are likely correct. In fact, they are positive that there is a genetic component to Chiari that can possibly be "cured." (What is meant by that I do not know...like you, I am not a scientist.)

Why no one is researching it??? That's a different question...

As a side note about research... in another thread I am going to post a request for anyone undergoing surgery with Dr. Henderson in the future.

8

This is something I’ve been thinking about to. My fiance has chiari and no one else in his family has any symtoms of chiari but I read that its hereditary. So then the gene or mutation can be dominent in some cases and not other? Why would that be is there another component? Other research I read says its a prenatal deficiency but is vague of what it is.

9

I found out in January that my oldest son has Marfans. I have a CM1. I was worried I might have passed on the chiari. I had no idea I gave him the Marfans. Someone should really research these things. I would have had my kids tested long ago, before my oldest ripped out his shoulder.

10

My son was told he didn’t have EDS. He was diagnosed with Marfans. I don’t meet the criteria for either.

11

Interesting! I’m Chiari, possible EDS Vascular. Recently diagnosed with FibroMuscular Displasia. Wonder if its connected? My son definitely has EDS! Don’t know of anyone else in my family though!

12

I am not a doctor, but my family is currently in Duke University research study for this. My self and two out of my three children have Chiari. Thankfully baby is not a chiarian.

But there has to be some genetic involvement if this “rare” brain formation is so intertwined in my family.

13

Hi TracyZ,

(To your previous post)

I did not see that listing on the trial website. Thank you for your update, and I really appreciate your feedback. Unfortunately, I am a singleton case of CM, so I wouldn't be able to help, either. From the information I've sought out, I'm with you on the idea that it really could be both. I wonder what the parameters of the study are at Duke, and what information they are comparing. Perhaps it's a combination of genetic factors, with more than one protein mutated? It's just too uncanny that multiple family members can be effected by the same disorder and it wouldn't be genetic. Perhaps there's not enough participants to compare data?

For us singleton cases, perhaps the autosomes are recessive in our parents, but it's brought out some how with prenatal vitamin deficiencies that triggers the mutations? This is all highly, highly speculative and unlikely, but I think it would be worth a discussion with a researcher as to why it wouldn't be feasible. I know the research isn't even there for hereditary cases, so we probably won't see research like this done in our lifetimes.

I thought it would be pertinent to note that there are a few variations of EDS that are not marked with COL5A1 or COL5A2 mutations. I think it would be incredibly interesting to see if these other EDS variations may be linked to another mutation on chromosomes 9 or 14, or even FBN1 itself. I am not a researcher by any means, but hopefully funding/interest may develop to see if Marfans, EDS and Chiari could be effected by the same or similar mutations in genes once hereditary markers are discovered.


TracyZ said:

Have you not checked the genetic research being done at Duke? I have recently been in email contact with the researcher and they have not identified a genetic marker for Chiari Malformations.The study started 2/1/10. US Clinical Trials have to be approved by a committee. Even if we all wanted to donate our DNA there is no guarantee we would find a researcher or they would ever get approval or funding to do the study. I work with & know a lot of researchers and NIH & DHH employees. It's very frustrating. NS & scientists are split over weather or not they think CM is genetic. I personally think it can be both. Mine is specifically not genetic in anyway. I will be interested to see others perspective, but in almost 4 years why hasn't Duke been able to prove a genetic marker if there is one?

http://www.clinicaltrials.gov/ct2/show/NCT01060800?term=chiari+malf...

14

Tracy, This is an amazing wealth of information, and I can't wait to get started on looking through this!

However, I am in the end-phases of getting ready for my wedding (for Oct. 19), so maybe after the excitement from that calms down, I can really get into this and find some more questions to ask.

Seriously, thank you for the links. I'm just excited to get a discusion going about this.

TracyZ said:

I have been thinking a lot about the FBN1 and the genetic component in CM and related disorders. We have several neurological Forums and often discuss cross over symptoms. I hope this research an answers some questions or makes you ask more. I have contacted a neurological researcher to see what we would have to do to get a study started.

Facts about Genetic Testing

[..]

15

You definitely got my attention with this! Just the other day my mom asked me about my headaches. Apparently my dad has been having some really bad headaches that don't always go away. He said they seem to start at the back of the skull down near where the neck is and usually move around to the front. We are thinking that maybe he has Chiari too. I urged him to talk to his doctor about getting an MRI since i have it. And now i have yet another place that i can send a message too with a few questions i want answered. (the neurologist i was sent to told me there was no need for me to have an office visit with him and i want a second opinion about that). But wow... i have some things to really research and think about now. Thanks!

16

Best Wishes Shasta on your upcoming wedding. Please post or message pictures. We love happiness. I am very happy for you& glad we have met. Where are you a Journalist? Mandy & I both do a lot of research and we have a male Member I will look for his name is a great researcher & so is Jozy and I am sure I have left out many Members.

Hi Fury...It's great to hear from you I hope you are doing well. Sorry your dad isn't feeling well. Message me if you need anything.

Everyone please read what Dr.Trumble wrote on the following Discussion on CM & EDS & genetics. It makes a lot of sense and answers questions of why it is so difficult to prove the genetic component. Very Interesting concept.

http://www.chiarisupport.org/forum/topics/curious-and-wondering?id=...

I am going to post this link on out Research Group so we don't lose it and can continue to add to it.

17

This is an interesting topic. Dustin is a single case, and current consensus is that his was likely caused by prematurity- he was born in early December with a due date in mid February in the early eighties. No one else in his family has exhibited clear signs of Chiari, though there are a few relatives he would like to see tested. Neither of our children has Chiari, and both have been tested, one at three years old by MRI, and our younger was checked at 19 weeks gestation through ultrasound.

18

Hey everyone!

Has anyone heard about possibilities we talked about in October?

Hope you are all doing well today. :)

19

Hi TracyZ!

Hope you're doing well. It's been a while since we've talked.

I'm a Journalist for a local daily paper in Altoona, PA. Have you found any other research that might link up with this topic?

This genetic research is something that's been in the back of my mind for a while.

TracyZ said:

Best Wishes Shasta on your upcoming wedding. Please post or message pictures. We love happiness. I am very happy for you& glad we have met. Where are you a Journalist? Mandy & I both do a lot of research and we have a male Member I will look for his name is a great researcher & so is Jozy and I am sure I have left out many Members.

Hi Fury...It's great to hear from you I hope you are doing well. Sorry your dad isn't feeling well. Message me if you need anything.

Everyone please read what Dr.Trumble wrote on the following Discussion on CM & EDS & genetics. It makes a lot of sense and answers questions of why it is so difficult to prove the genetic component. Very Interesting concept.

http://www.chiarisupport.org/forum/topics/curious-and-wondering?id=...

I am going to post this link on out Research Group so we don't lose it and can continue to add to it.

20

This topic does interest me to. My son is starting to complain of headaches and dizziness and hes about the same age I first started getting headaches. I don’t want to dismiss them but at the same time I’m not sure if we should ask his dr to do an mri or not.