Thank you Fred Kaplan!

I would like to thank Dr. Fred Kaplan, the world's top FOP researcher, for helping me with this project!  Your interview was extremely beneficial to my overall understanding of FOP.

 

If you would like to learn more about Fred Kaplan and his work with IFOPA, please visit the IFOPA Researchers.

Why is FOP research important?

I know what you all are thinking.  FOP only affects 1 in 2 million people.  So, why don't we focus on funding more common diseases like Hemophilia or Down Syndrome?  Well, there is nothing wrong with that.  In fact, I encourage it. 

 

However, unlike many disorders, where research is confined to that specific disorder, increased FOP research helps benefit research in other bone-related issues, like osteoporosis.

 

 

In osteoporosis, bone mass decreases, which can lead to an increased risk of fracture.  The more scientists study into the ACVR1 gene and its control of the bone morphogenetic proteins (BMPs), the more they understand how ossification works.  This critical information can help scientists figure out how to facilitate new bone growth for those in need of it, such as those with osteoporosis.

 

So, what can YOU do to help?

 

I know this may seem to simple, but all you need to do to help FOP patients is spread the word.  Not just about FOP, but about all genetic disorders.  Raising general awareness of these diseases is of the utmost importance - it is more important than fundraisers and donations because in the end

AWARENESS=MORE FUNDING...

 

And that is exactly what I hoped to accomplish with this blog.  I hope you enjoyed learning about FOP and I hope I was successful in teaching  you about the terrifying disease.

 

If you would like to help out even more, visit IFOPA to become a member, donate, and become part of the community.

 

 

 

Interesting Facts about FOP

• The University of Pennsylvania School of Medicine is the only laboratory in the U.S. dedicated to FOP research
• $1.5 million every year is spent on FOP research
• 75% of the funds come from FOP family fundraising and donations
• 25% of the funds come from institutional support
• The International FOP Association funds the University of Pennsylvania School of Medicine with $500,000 annually
• FOP literally means "soft connective tissue that progressively turns to bone"
• FOP was originally known as "Myositis ossificans progressiva", which means "muscle turns progressively to bone
• FOP doesn't affect brain activity or IQ
• FOP does not affect smooth muscle tissues
• Intestines
• Eye muscles
• Respiratory tract
• Stomach
• Bladder
• Cardiac muscles
• There was a petition for government funding of FOP at Oxford University in 2013
• Of the 100,000 signatures needed to pass the petition, only 1,086 signatures were sent

The Personal Side of Stone Man Syndrome

The everyday life of individuals suffering from Stone Man Syndrome varies. 

 

FOP does not affect brain activity, so people with it do not have any learning or working disabilities, at least, none caused by FOP.  Problems arise when the physical aspects of work and school come into play.  Students with FOP must be able to "safely access the school premises, use and manipulate the school's materials, and function academically."  People with FOP must be handled with care to prevent an accidental fall or a strain of the neck.  Many patients must travel in a wheelchair to prevent just these accidents from occurring.

 

Despite these risks, some people with FOP can live a normal life with no extreme flare-ups of bone growth.


I have found some great organizations and resources that can help families cope with FOP.
 

 International FOP Association

Eurordis

Friends of Oliver

Friends with FOP

And above all, here is a comprehensive guide over FOP, given to me by Fred S. Kaplan, the world's leading expert on anything and everything FOP.

FOP Guidebook for Families

 

Treatment and Life Expectancy

As I mentioned in a previous post, people afflicted with FOP get flare-ups of bone tissue that usually last for a few weeks. 



Ossified body on right; X-ray of feet on left

Exterior view of bone growth

There are currently no known treatments for these flare-ups, only drugs and medications can be used to deal with the pain.  Surgery is an option; however, this often leads the body into thinking that the tissue has been damaged and this results in the formation of more bone by the FOP receptor proteins.

Corticosteroids are used to control swelling and pain caused by flare-ups. Cox-2 inhibitors and NSAIDS (Non-Steroidal Anti-Inflammatory Drugs) are used when long-term treatments are required.

Regardless of the treatment, care must be taken at all times.  As with surgery, any tissue damage, even as minor as a bruise, may send a signal to the receptors to begin bone creation.

 

Life Expectancy:

 

People with FOP don't necessarily have a life expectancy set in stone.  Most FOP patients have died before they reached 40 years of age.  However, a few have lived to be over 60.  It truly comes down to the conditions and circumstances in which they live.  There is nothing preventing people with FOP to live as old as those without it, but with as easy as it is to facilitate bone growth through damaged tissues, many people become paralyzed within their own body by the time they reach 25.

The Genetics of FOP

Fibrodysplasia ossificans progressiva is a autosomal dominant disorder that is most commonly acquired through spontaneous mutations of a specific gene found on chromosome 2. 

 

Dominance is really just the relationship between two "alleles" on a certain gene, with one allele expressing dominance over the other.

 

The gene in question, Activin Receptor Type 1A (ACVR1), is a protein in the cells that controls bone morphogenetic proteins (BMP's).  The random mutation changes codon 206 from arginine to histidine on the receptor protein.

 

In essence, the mutation changes the receptor protein to encode the BMP's to create an extra skeleton.

As FOP is a spontaneous mutation, there will not necessarily be a previous family history with the disorder in order for it to pop up.  Very few FOP cases are inherited from parents because most people afflicted with FOP either are unable or choose not to have children.

One thing you must know about FOP: you either have it or you don't!  Such is the case with autosomal dominant patterns.

Next, I am going to show you a few situations using Punnett Squares.  If you do not know how to follow Punnett Squares, please view http://mhhe.com/biosci/genbio/virtual_labs_2K8/pages/PunnettSquares.html to get a basic understanding of them.

F=FOP
f=Normal
FF=Homozygous Dominant (will have FOP)
Ff=Heterozygous (will have FOP)
ff=Homozygous Recessive (will not have FOP)

An FF male with FOP has children with an ff normal female.
Child Results: Ff, Ff, Ff, Ff
Therefore, all of their children will be afflicted with FOP because the dominant F is expressed.

An ff normal male has children with an Ff female with FOP.
Child Results: Ff, ff, Ff, ff
Therefore, there is a 50% chance of their children having FOP because the dominant F is expressed in half of the results.

An Ff male with FOP has children with an Ff female with FOP.
Child Results: FF, Ff, Ff, ff
Therefore, there is a 75% chance of their children having FOP because the dominant F is expressed in 3/4 of the results.

Statistics

 Scientists estimate that 1 in 2 million people are afflicted with FOP worldwide.
This is an estimated 2,500 to 3,500 cases.  To put this into perspective, you would have to fill 20 football stadiums, housing 100,000 people each, to find one person with FOP.

If you found the out-of-place dot, then you found one person with FOP in a crowd of 2 million people.

There have been about 800 confirmed cases of FOP globally.
About 30% of these cases come from the U.S. alone.

FOP does not follow any ethnic, racial, or gender patterns whatsoever. 

Anyone can get it.

 

Diagnosis and Testing

Despite sometimes obvious symptoms, like the malformation of the big toe, FOP is extremely difficult to diagnose properly.

 

Due to the rarity and the lack of knowledge of FOP, 80% of FOP patients are misdiagnosed!

 

FOP is commonly misdiagnosed with...

 

1. Cancer - doctors mistake benign tumors with malignant tumors.

2. Aggressive juvenile fibromatosis - doctors mistake the appearance of benign soft tissue tumors with bone tumors.

And although rare...
 

3. Fibrous dysplasia - doctors mistake the swelling of bone tissue causes by small bone cells weakening the bone structure with benign tumors.

FOP is most often diagnosed before the age of 10. 

 

For more information regarding misdiagnosis, visit http://www.ifopa.org/what-is-fop/misdiagnosis.html.

 

Or watch this documentary about a real-life FOP diagnosis...

 

 

 

 

 

 

Testing

 

Sequence analysis of entire coding region: Laboratory for Molecular Diagnostics Center for Nephrology and Metabolic Disorders.
Weisswasser, Sachsen, Germany

Deletion/duplication analysis: Clinical DNA Testing and DNA Banking Prevention Genetics.

Marshfield, WI, United States

 

Targeted mutation analysis: Medical Genetics Unit Genomic Systems.
Paterna, Comunidad Valenciana, Spain

 

Targeted variant analysis: Genetic Diagnostic Laboratory.
Philadelphia, Pennsylvania, United States

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The International FOP Association donates most of its funds to this laboratory.