Fibrodysplasia Ossificans Progressiva (FOP): An Overview
Published: Last Edited:
Disclaimer: This essay has been submitted by a student. This is not an example of the work written by our professional essay writers. You can view samples of our professional work here.
Any opinions, findings, conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of UK Essays.
- David Hong
As a person diagnosed with the FOP disease, life is hard to live day by day. When I was first born, I had malformed big toes that were short and bent inward, and as a child my back felt stiff and I had difficulty crawling and moving around. One day, I was running around the yard and fell on my back area from tripping. At first, the pain was endurable but as the day passed, inflamed swellings and nodules arose. The sensation of painful flare-ups on my back area lasted couple weeks until I noticed that the swelling left behind a newly formed bone in my skeleton. Shocked, my parents quickly took me to the hospital where I was diagnosed. At first the doctor told me my disease was due to cancer, and thus I had to go through numerous chemotherapies. But after a while, the doctor told me that I had the juvenile fibromatosis and again went through more surgeries and unnecessary therapies. Then again I was diagnosed with a new disease called progressive osseous heteroplasia in which I had to go through new invasive procedures that led to more complications. Day by day the disease grew worse, as it spread down to my trunk and limbs of the body and replaced my muscles with bones. Thus by my teenage years, I was paralyzed and had to be transported with the wheelchair. But one day I met a new doctor who diagnosed my body and discovered that I had the disease called Fibrodysplasia Ossificans Progressiva, a rare genetic disease that causes skeletal malformations and progressive heterotopic ossification (bone formation), and is often misdiagnosed by more than 80 percent of doctors. Sadly, he told me and my parents that there is no effective treatment for FOP and surgeries removing the excess bones are not applicable since it can results in more bone formation with greater speed. However, he said researchers are investigating FOP and new treatments, and they are currently developing drugs that may control bone growth. But meanwhile I can relieve my swelling symptoms and pain with medication, and I am waiting for the cure to be discovered.
FOP or fibrodysplasia ossificans progressiva basically means “soft connective tissue that progressively turns to bone.” The first case of this disease was reported in 1692 by a French physician named Guy Patin who encountered a patient with the FOP disease and wrote about the man in his writings to his colleagues. Then in 1736, a British physician named John Freke of Saint Bartholomew’s Hospital wrote about a normal 14 year old boy who had swellings all over his back from the bottom of his spine to the neck that joined together all parts of his back like “a fixed bony pair of bodice.” Other doctors like Jules Rosenstirn from Mount Zion Hospital in San Francisco in 1918 also came across similar cases from her patient. The disease originally was known as myositis ossificans progressiva which means “muscle turns progressively to bone.” However, in the 1970s, Dr. Victor McKusick of Johns Hopkins University School of Medicine modified the name to fibrodysplasia because he stated that not only muscles but other soft tissues were replaced by bones also.
FOP is considered to be one of the rarest diseases in the world and thus it is often misdiagnosed. The disease is believed to occur in approximately 1 in 2 million people worldwide and only about 700 hundred cases have been confirmed as the FOP. However, one of the most famous FOP patients was Henry Eastlack Jr. (1933-1973). The FOP began to affect him since the age of 10 and by the age of 40 his entire body fused into one continuous block and completely ossified due to extra bone growth. He could only move his lips and six days before his birthday he died of pneumonia. However before Eastlack died, he wanted to donate his body to science so people can find a cure to the disease which he suffered from. Now, his skeleton is displayed at the Mutter Museum of the College of Physicians in Philadelphia which many FOP scientists use for reference and research.
There are many outward symptoms of having the FOP disease. At birth, children with the FOP often have malformed big toes that are short, bent, and curved inward. Also, kids with FOP cannot crawl because the facet joints in the back of the neck are deformed or fused which limits the child’s movement. FOP begins in the neck and shoulders and progresses along the back, trunk, and limbs of the body. These symptoms of FOP usually begin during the first two decades of life. And inflamed swellings, usually in the shoulder and back areas and sometimes on the scalp or head, are usually the first sign of FOP. After swellings clear up, they leave behind a newly formed, mature bone. However, rate of bone formation and growth and the location of growth differ for each person. Most times, Nodules (tumor-like swellings) often develop after a child experiences some sort of trauma to the body like a bump or fall.  And often, these nodules or bumps transform into bone during a process called heterotopic ossification. People feel a painful flare-up when the body starts to generate new bone, which can last up to 8 weeks. Then the disease moves to the trunk and limbs of the body and eventually replaces the body’s muscles with a bone.
The FOP disease has no ethnic, racial, or geographic predisposition or sex predisposition. It is an extremely rare disease that has a worldwide prevalence of approximately 1 case in 2 million individuals. Although most people with FOP are born with the disease in rare cases one can have the disease from a sudden mutation in the ACVR1 gene.
Genetic Cause of the Disease
It has been hypothesized that the missense mutation in the ACVR1 gene causes fibrodysplasia ossificans progressive because they have not yet pinpointed the exact mutation. “The ACVR1 gene provides instructions for producing a member of a protein family called bone morphogenetic protein (BMP) type I receptors.” The ACVR1 gene is found in many tissues of the body and helps to control the growth and development of bones and muscles and ossification of bones in normal skeletal maturation. However, “researchers believe that a mutation in the ACVR1 gene may change the shape of the receptor under certain conditions and disrupt mechanisms that control the receptor's activity.” Thus the receptor may be turned on all the time and cause overgrowth and production of bones, cartilages, and fusion of joints.
The ACVR1 gene that is responsible for the production of type 1 receptor proteins can be found in the molecular location on chromosome 2.
Surprisingly, the FOP disease is “inherited in an autosomal dominant pattern,” thus only one copy of the mutated gene is enough to cause the disease. However, it is researched that most cases of FOP is caused from a new, spontaneous mutations in the gene that “occur in people with no history of the disorder in family.” But in small number of cases, an affected person has inherited the mutation from one affected parent.
Autosomal Dominant Example
Due to the rarity of the disease, researchers have not yet pinpointed the definite mutation that causes the change in amino acid sequence. However, it is believed that a missense mutation in the ACVR1 gene has caused the nucleotide to change and code for a different conserved amino acid sequence, which results in the mutation of the BMP type 1 receptor proteins.
Researchers largely believe that the mutation in the ACVR1 gene caused the changes in shape of the BMP type 1 receptor proteins which can mutate the receptor’s activity. As a result, “the receptor may be constantly turned on (constitutive activation) that causes overgrowth of bone and cartilage and fusion of joints, resulting in the signs and symptoms of fibrodysplasia ossificans progressiva.”
Usually, BMP receptors span the cell membrane, so that one end of the protein remains inside the cell and the other end projects from the outer surface of the cell. This arrangement allows receptors to receive signals from outside the cell and transmit them inside to affect cell development and function. However:
Both leaky activation of BMP signaling and accumulation of BMP type I receptors at the cell membrane are seen in FOP cells, suggesting possible aberrant association with FKBP12 in FOP. The most likely possibility is that FKBP12 interactions with the GS domain become altered, leading to promiscuous ACVR1/ALK2 activity.
Thus in the cell membrane, there is a leaky activation of BMP signaling and amass of BMP type 1 receptors when FOP disease is present.
In terms of the effect on the organism level of the disease, the term progressive represents the fact that the FOP disease becomes progressively worse. At the end, most of the soft tissues will be ossified into bones due to the overgrowth of BMP type 1 receptor proteins. The swellings and painful flare-ups often indicate the formation of a new bone and occur every time when a new bone is forming. Meanwhile as new bones grow both inside and outside the skeleton, the person becomes paralyzed and eventually unable to move at all. As a result, most patients with fibrodysplasia ossificans progressiva are transported by a wheelchair and require lifelong assistance in performing activities of daily living.
Currently, there are no official treatments that can cure the disease. The only source of medications available is those that can relieve the symptoms of FOP, such as pain and inflammation and relax the muscles. However, in October 2011, scientists at the Research for FOP and Related Disorders at the University of Pennsylvania made a promising discovery. By “using a small sequence of ribonucleic acid (RNA), a macromolecule similar to DNA, scientists were able to block the damaged copy of the ACVR1/ALK2 gene, while leaving the healthy copy untouched.” Thus the procedure caused the ACVR1/ALK2 cellular activity to become normal. However, the scientists have not yet discovered an efficient and safe method of delivering the RNA molecules to cells in the human body. On the other hand, you can also take regularly cautionary measures that prevent further spread of the disease, such as avoiding deep tissue trauma, taking intubation precautions, and consulting expert doctors.
Resources for Patients and their Families
If someone is suffering through the FOP disease, don’t hesitate to seek help and acquire more detailed information about the disease. You can join the International Fibrodysplasia Ossificans Progressiva Association and fund research, find a cure, and support other families who are suffering the same problem. You can visit their website and also call them. In addition, the UCSF Benioff Children’s Hospital provides information about the disease, symptoms, diagnosis, and treatment of the FOP disease as well.
You can also visit the Office of Rare Diseases Research website, a government sponsored website that is dedicated to all rare diseases, to know about the health care professionals or researchers who have knowledge of their conditions. They provide a “How to Find a Disease Specialist” fact sheet that provide ways to seek healthcare professionals who have experience with a particular condition.
Campobasso, Paul. “Fibrodysplasia Ossificans Progressiva: Stone Man Syndrome,” Suite 101 Last modified January 03, 2012. https://suite101.com/a/fibrodysplasia-ossificans -progressiva -stone-man-syndrome- a400243.
“Fibrodysplasia Ossificans Progressiva,” The Medical Bag. Last modified September 27, 2012. http://www.themedicalbag.com/raredisease/fibrodysplasia-ossificans- progressiva.
“Fibrodysplasia Ossificans Progressiva,” UCSF Benioff Children's Hospital. n.d. Accessed January 30, 2014. http://www.ucsfbenioffchildrens.org/conditions/fibrodysplasia_ ossificans _progressiva/.
“Fibrodysplasia ossificans progressiva,” U.S. National Library of Medicine. Last modified August 2007.http://ghr.nlm.nih.gov/condition/fibrodysplasia-ossificans-progressiva.
“Fibrodysplasia ossificans progressiva,” Wikimedia Foundation Inc. Last modified August 2013. http://en.wikipedia.org/wiki/Fibrodysplasia_ossificans_ progressiva.
“IFOPA,” International Fibrodysplasia Ossificans Progressiva Association. n.d. Accessed January 30, 2014. https://www.ifopa.org/.
Kaplan, Frederick, Eileen Shore, and Chakkalakal Salin. “Fibrodysplasia ossificans progressiva: mechanisms and models of skeletal metamorphosis,” The Company of Biologists. Last modified 2012. http://dmm.biologists.org/content/5/6/756.full?sid=49453f1e-087b-4a02-8011-8e6767dfc6a7.
Kaplan, Frederick, Martine Merrer, David Glaser, Robert Pignolo, Robert Goldsby, Joseph Kitterman, Jay Groppe, and Eileen Shore.“Fibrodysplasia ossificans progressiva,” National Institute of Health. Last modified March 2008. http://www.ncbi.nlm.
Pignolo, Robert, Eileen Shore, and Frederick Kaplan. “Fibrodysplasia Ossificans Progressiva: Clinical and Genetic Aspects,” Orphanet Journal of Rare Diseases. Last modified 2011. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3253727/?tool=pubmed.
Pignolo, Robert. “Pediatric Fibrodysplasia Ossificans Progressiva (Myositis Ossificans),” WebMD Health Professional Network. Last modified September 19, 2013. http://emedicine. medscape.com/article/1007104-overview.
 “History of FOP,” International Fibrodysplasia Ossificans Progressiva Association. n.d. Accessed January 30, 2014. https://www.ifopa.org/.
 “Fibrodysplasia Ossificans Progressiva,” The Medical Bag. Last modified September 27, 2012. http://www.the medicalbag.com/raredisease/fibrodysplasia-ossificans- progressiva.
 Robert Pignolo. “Pediatric Fibrodysplasia Ossificans Progressiva (Myositis Ossificans),” WebMD Health Professional Network. Last modified September 19, 2013. http://emedicine.medscape.com/article/1007104-overview.
 “Fibrodysplasia ossificans progressiva,” Wikimedia Foundation Inc. Last modified August 2013. http://en.wikipedia.org/wiki/Fibrodysplasia_ossificans_ progressiva.
 “FOP Symptoms,” International Fibrodysplasia Ossificans Progressiva Association. n.d. Accessed January 30, 2014. https://www.ifopa.org/.
 “Fibrodysplasia Ossificans Progressiva,” UCSF Benioff Children's Hospital. Accessed January 30, 2014. http://www.ucsfbenioffchildrens.org/conditions/fibrodysplasia_ossificans_progressiva/.
 Paul Campobasso. “Fibrodysplasia Ossificans Progressiva: Stone Man Syndrome,” Suite 101. Last modified January 03, 2012. https://suite101.com/a/fibrodysplasia-ossificans-progressiva-stone-man-syndrome- a400243.
 “Fibrodysplasia ossificans progressiva,” U.S. National Library of Medicine. Last modified August 2007. http://ghr.nlm.nih.gov/condition/fibrodysplasia- ossificans-progressiva.
 Robert Pignolo, Robert, Eileen Shore, and Frederick Kaplan. “Fibrodysplasia Ossificans Progressiva: Clinical and Genetic Aspects,”Orphanet Journal of Rare Diseases. Last modified 2011. http://www.ncbi.nlm.nih.gov/pmc/articles /PMC3253727/?tool=pubmed.
 Frederick Kaplan, Martine Merrer, David Glaser, Robert Pignolo, Robert Goldsby, Joseph Kitterman, Jay Groppe, and Eileen Shore. “Fibrodysplasia ossificans progressiva,”National Institute of Health. Last modified March 2008.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2424023/.
 Frederick Kaplan, Eileen Shore, and Chakkalakal Salin.“Fibrodysplasia ossificans progressiva: mechanisms and models of skeletal metamorphosis," The Company of Biologists. Last modified 2012. http://dmm.biologists.org /content/5/6/756.full?sid=49453f1e-087b-4a02-8011-8e6767dfc6a7
 “Treatment Guidelines,” International Fibrodysplasia Ossificans Progressiva Association. Accessed January 30, 2014. https://www.ifopa.org/.
Cite This Essay
To export a reference to this article please select a referencing stye below: