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Bet
17th November 2009, 07:48 PM
Just been onto the Human Chiari Site ,and wondered if this information would of a wee bit of interest.

Published 31-7-09.

For several years now Researchers have been using MRI's to Measure Skull Base Dimensions of Chiari Patients in what is know as Morphometrics ,this measures Dimensions of the Skull and the Brain.

The Theory that has emerged is that ,that the Brain is not too Big for the Skull ,but that the Skull is too Small for the Brain

French Researchers have just published their findings,and have made an interesting point ,namely that if the Skull Abnormalities found with Chiari are due to a defect in the early Embryo ,why is there such a range in the age when Symptoms become apparent?

Why is'nt Everyone Symptomatic at a very early age?

One possibility ,as the Authors note, is that there are actually different Mechanisms which can lead to a Mismatch between the Skull and the Brain.

For example ,some Skull Sutures don't fully close until late Teens or Adulthood which could push back Symptoms.

This would imply Chiari is actually a Dynamic Phenomenon,and there are case Studies to support this View

The Paper goes onto mention ,however ,another possibility is that crowding alone does'nt always lead to symptoms .

For example ,perhaps ,perhaps over time Scar Tissue and Adhesions build up which then lead to Symptoms

Could we substitute Cavaliers for Humans in this Paper, could it be making sense. ?

EddyAnne
18th November 2009, 12:52 AM
Could we substitute Cavaliers for Humans in this Paper, could it be making sense. ?
Bet I think that Research with Cavaliers could be of help to Humans, and Research with Humans could be of help to Cavaliers.

Some time ago I noted that Geneticist Professor Dr. Guy Rouleau in Montreal works in a Research Facility for Human yet he is involved in finding the CM/SM genes in Cavaliers, and that the results from this could also be of help to Humans. Via this link I even watched him talk about "Chiari Genetics: Dogs & Humans".
http://hosted.mediasite.com/hosted5/Viewer/?peid=b8de06e52e5c4e0982c4194979a43e63

Also I've noticed some other things like Dr. Clare Rusbridge receiving a cheque from the Ann Conroy Trust which is for Humans, and we know that Clare is a Veterinary Neurologist, see via this link where Neurosurgeon Dr. Graham Flint is seen presenting the cheque and I think that he operates on Humans at The Queen Elizabeth Hospital in Birmingham.
http://www.veterinary-neurologist.co.uk/act_trust.htm

Due to things like the above others think that Research with Cavaliers could be of help to Humans, and Research with Humans could be of help to Cavaliers.
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Bet
18th November 2009, 10:46 AM
Now here's a thought.

As has been said in a Theory by Researchers into the Human Chiari Problem ,,that it's not the Brain is too Big for the Skull ,but rather that the Skull is too Small for the Brain.

Just supposing that this is also the reason for the Cavaliers' Problem.

I think many Cavalier Folk are now agreed that the Cavaliers' Heads are Smaller than they were 20 years ago.

So ,if that could be the Reason for CM/SM in Cavaliers, could a solution be to Out-Cross with Cocker Spaniels, they have Bigger Heads.

I know that this Out-Crossing was done in the early 1950's, with Crest by Candlelight ,Cavalier and Suntop Joyful ,Cocker Spaniel.

There could be the Problem from some Cocker Spaniels with the Condition Cocker Rage, but if to save the Cavalier Breed from the Insidious SM Disease, is this not worth a thought.

I know that the EBV Scheme is giving hope for the future of Cavaliers, but could not the danger of Carrier to Carrier be being mated to-gether be involved,but with Out Crossing there probably won't be the same risk.

Has the time now come for the Cavalier World to decide that this maybe could be a way forward for the Breed if the Cavaliers have to have a future .

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EddyAnne
18th November 2009, 06:28 PM
I think many Cavalier Folk are now agreed that the Cavaliers' Heads are Smaller than they were 20 years ago.

Bet are Human Heads Smaller than what they were 20 years ago?

I think that DNA Research is going to look very closely at "Fibrillin-1" in Humans and Cavaliers plus the Griffons as previous DNA Research did find this.
Abstract
Chiari type I malformation (CMI; OMIM 118420) is narrowly defined when the tonsils of the cerebellum extend below the foramen magnum, leading to a variety of neurological symptoms. It is widely thought that a small posterior fossa (PF) volume, relative to the total cranial volume leads to a cramped cerebellum and herniation of the tonsils into the top of the spinal column. In a collection of magnetic resonance imagings (MRIs) from affected individuals and their family members, we measured correlations between ten cranial morphologies and estimated their heritability in these families. Correlations between bones delineating the PF and significant heritability of PF volume (0.955, P = 0.003) support the cramped PF theory and a genetic basis for this condition. In a collection of 23 families with 71 affected individuals, we performed a genome wide linkage screen of over 10,000 SNPs across the genome to identify regions of linkage to CMI. Two-point LOD scores on chromosome 15 reached 3.3 and multipoint scores in this region identified a 13 cM region with LOD scores over 1 (15q21.1-22.3). This region contains a biologically plausible gene for CMI, fibrillin-1, which is a major gene in Marfan syndrome and has been linked to Shprintzen-Goldberg syndrome, of which CMI is a distinguishing characteristic. Multipoint LOD scores on chromosome 9 maximized at 3.05, identifying a 40 cM region with LOD scores over 1 (9q21.33-33.1) and a tighter region with multipoint LOD scores over 2 that was only 8.5 cM. This linkage evidence supports a genetic role in Chiari malformation and justifies further exploration with fine mapping and investigation of candidate genes in these regions.
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Bet
19th November 2009, 10:24 AM
EddyAnne,

If you or any one else is interested ,the information I posted can be found at

www.conquerchiari.org

What was mentioned ,was the Theory that a Significant number of Human Chiari cases ,if not a Majority ,are caused by an undervelopement of the Skull in the Occipital Area

There have been contradicting findings of the patients with Chiari and Smaller Posterior Fossas ,the sizes have been different.

Because of this ,Researchers are still exploring different ways to analyze the Relative size of this Skull Region,

Some have tried using a Volumn Ratio of Skull to Brain Tissue,while others have turned to Measuring Specific Bone Segments as opposed to General Volumn Measurements.

I don't know if this information will help our Cavaliers ,all I know ,and others agree ,that many of the Cavaliers' Heads are Smaller than they were 20 years ago.

As I have mentioned ,many have a Deeper Stop, and that is against the Cavalier Breed Standard Requirements, which says Cavaliers should have a Shallow Stop.

Whether having a Deeper Stop is influencing the Smaller Heads ,I don't know, but I think this is due to what the Cavalier Breeders want now-a-days. This type of Cavalier Head has been Breeder made, not due to Genes.

Bet
19th November 2009, 11:03 AM
Just had to add this, there is an interesting Article in this week's Dog World by Jessica Holmes about Out -Crossing, maybe my thoughts about trying to help the SM Problem in Cavaliers ,now that it's been acknowledged that their Heads are too Small for their Brains, is to involve some Cocker Spaniels because they have Larger Heads and some Cavaliers with an Out- Crossing Program,this would have to be strictly controlled, but would it not be worth a try to find out if this type of Breeding could help in the fight against SM in Cavaliers.

Clairelou
19th November 2009, 03:03 PM
Just had to add this, there is an interesting Article in this week's Dog World by Jessica Holmes about Out -Crossing, maybe my thoughts about trying to help the SM Problem in Cavaliers ,now that it's been acknowledged that their Heads are too Small for their Brains, is to involve some Cocker Spaniels because they have Larger Heads and some Cavaliers with an Out- Crossing Program,this would have to be strictly controlled, but would it not be worth a try to find out if this type of Breeding could help in the fight against SM in Cavaliers.

Thaks as always for bringing this to our attention Bet :)
I can't find this article on the dog world website, was it in newspaper format you read this?

RodRussell
19th November 2009, 03:59 PM
...I think many Cavalier Folk are now agreed that the Cavaliers' Heads are Smaller than they were 20 years ago.

I don't agree with that at all, speaking solely anecdotally. Our experience with Cavaliers goes back 40 years, and our Cavaliers with the largest heads, particularly the males, have been the current generation.

EddyAnne
19th November 2009, 07:02 PM
Bet breeders can breed for a smaller head but I do NOT think that this caused Chiari to appear in the Cavalier breed nor in the Human breed. I think that Chiari originally appeared in both Humans and Cavaliers probably due to similar reasons.

Bet you mentioned to have a read of the Conquer Chiari website which is for Humans. Yes I had a read of some articles and I even noted that "Fibrillin-1" is mentioned at this link address.
http://www.conquerchiari.org/subs%20only/volume%204/issue%204(10)/chiari%20gene%204(10).asp

On Dr. Rusbridge's website I noticed "Fibrillin-1" is mentioned and the following is from this link address, and "Fibrillin-1" is also mentioned on the Cavalier Club website and even in Dr. Rouleau's video presentation at the Chiari Conference.
http://www.veterinary-neurologist.co.uk/research.htm

Finding the gene(s) for Chiari malformation
Investigation of possible candidate gene - Fibrillin 1
Genetic studies in humans with Chiari malformation type 1 have indicated significant areas (high LOD scores) on chromosomes 9 and 15 (for more information click here). On chromosome 15 there is a very large gene called Fibrillin- 1 which has already been associated with genetic conditions that involve mis-shapen skulls including Marfan syndrome and Shprintzen-Goldberg syndrome (the defects in this syndrome include CM). Fibrillin has been suggested as a possible positional candidate gene. It is very large gene coding for an amino acid which is a constitutive element of extracellular microfibrils in connective tissues. Fibrillin 1 sequence analysis in affected CKCS, Yorkshire Terrier, Bull Terrier, Boston Terrier, Chihuahua, Brussels Griffon and King Charles breeds is ongoing.
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Bet
19th November 2009, 07:11 PM
I don't want to argue with you Rod about my Statement that Cavaliers have Smaller Heads than they had about 20 years ago, maybe not in America, but they sure do here in Britain.

For example, Pargeter, Maxholt, Crisdig ,and they did'nt have the Deep Stop either that many of to-day's Cavaliers have.Even the APGAW Committee have mentioned about the Cavaliers having Small Heads, in the PDE TV Film mention ,mention was made about the Cavaliers' Brains, it was like getting a size 10 foot into a Size 6 shoe.

According to the Cavalier Breed the Cavaliers should have a Shallow Stop.

Th article written by Jessica Holm,is on the Home Page of Dog World, scroll down and you should get it.

EddyAnne
19th November 2009, 11:45 PM
a size 10 foot into a Size 6 shoe.

On Chromosome 15 there is a very large gene called Fibrillin-1 which has already been associated with genetic conditions that involve mis-shapen skulls that include Chiari Malformations. Could that gene be causing problems in Cavaliers described as "a size 10 foot into a Size 6 shoe", this maybe even starting in the embryonic stage of development where tissue and structures are being formed and where genes do contain heaps of information including sizes of things being developed?
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