Written by Dave Page
Out of all the strange and unusual conditions we have covered, Münchmeyer disease, also known as “Fibrodysplasia Ossificans Progressiva (“FOP” or “Stoneman Disease”) may well be the strangest. We’ll be using the term FOP from here onwards to avoid any confusion. In today’s episode we will take a look at exactly what this disease is, how it is caused and what happens to the unfortunate individuals who receive a positive diagnosis.
What is FOP?
FOP is an incredibly rare condition which causes muscles, tendons and ligaments to be turned into bone. According to web MD, “A glitch in one of the genes that tells your body how to grow your bones and muscles causes the condition. It’s actually part of normal growth that some soft tissue turns into bone. But with this problem in your gene, bone grows too often and too much.”
FOP usually starts to show during early childhood, with the most common symptom (stunted or deformed growth of the big toes) being present at birth, and similar deformities in the thumbs also present in 50% of cases. Although the condition can be detected with a simple blood test, due to its exceptional rarity it is often misdiagnosed as Aggressive Juvenile Fibromatosis, also called Desmoid Tumors, which is a rare form of cancer that attacks the tendons and ligaments. The reason behind this frequent misdiagnosis is that patients who are suffering from either condition will develop painful growths on the neck, shoulders and upper back. This kind of misdiagnosis can have serious consequences, mainly because anything that triggers the body’s healing process, such as an injection or biopsy can cause FOP to flare up and make things much worse. In extreme cases, missing the diagnosis has led to limbs being amputated and this not only affects the patient’s quality of life because they have to adapt to living life with a missing limb, but also the resulting physical trauma from the surgery invariably causes the exacerbation of bone growth and all the previously mentioned difficulties that come along with it.
Because of the extreme volatility of this condition, it is almost impossible for sufferers to lead anything close to a normal life. Take, for example, your average toddler. As any parent knows, even the process of learning to walk will result in many falls, banged heads and other minor injuries. Ordinarily, this presents no real problems and is simply a part of growing up. However, for a child suffering from FOP, even the slightest bruise can result in the affected tissue being replaced with bone. Terrifyingly, this is only the beginning. As the disease progresses, more and more of the body’s soft tissues are transformed. This eventually results in limbs being frozen in place, the fusing together of the bones that make up the spine, and the jaw being rendered completely immovable making it extremely difficult to eat or talk. One sufferer, when asked by a reporter to describe just what it feels like to have FOP would say:
“Imagine not only being confined to a wheelchair for the rest of your life but being trapped in a seated position because your joints have fused that way. Imagine going to sleep every night not knowing if when you wake up in the morning you will have full use of your arms. Imagine being able to eat normally one day and then two days later not being able to move your jaw. These are just some of the challenges I have been through so far.”
Ultimately, sufferers usually succumb to heart failure or respiratory issues when the disease becomes so advanced that the extra bone growth prevents the chest cavity from expanding. In the past, people would often undergo surgery to have excess bone removed and, although this would often result in temporary improvement, the trauma caused by the surgery would always result in the bone regrowing in greater quantities than before.
One lady who was born with the condition and spent 12 years as a case study for Yale Medical School said in an interview with Behind The Mystery:
“During a flareup in my left arm, they injected steroids directly into the muscle along with the surgery they tried on my right elbow, and it released the tendons, and it was fabulous! I had wonderful motion in my arm and then six months later my arm flared up and it contracted more than it was prior to the surgery.”
As if dealing with your body slowly freezing up wasn’t enough, this extra bone growth can be debilitatingly painful. One man described it as “like your entire body is filled with shards of broken glass. Every time you move, the jagged bone fragments rub or pinch your remaining soft tissues. Some days it is almost too much to bear.” Other complications may also arise with the senses. In approximately 50% of cases, sufferers will develop partial or complete hearing loss due to extra bone forming within the delicate structure of the ear.
On top of all that, the effects of FOP can be very visually noticeable, and this can generate a lot of unwanted attention which can be very difficult to deal with, especially for young children. One account from the mother of a three-year-old boy suffering from advanced FOP is particularly heart breaking: “He does not understand why other children treat him differently. Sometimes it’s fine but other times kids will make fun of him or refuse to play with him purely because of how he walks or how he looks.”
Childhood can be particularly difficult for those who suffer with FOP as the resulting injuries from something as mundane as falling off a bike can result in extra bone growth that can cause a knee or elbow to become permanently paralysed. According to one source, this can happen overnight. “I was suffering from a flare up in my knee. I decided to go to bed early to rest and try and get a good night’s sleep but when I woke up, my knee joint was completely frozen. I have never been able to move it since.”
The medical community has been aware of FOP for centuries, with the earliest written records dating back to 1692 and one Dr Guy Patin documenting a young patient of his who turned into wood, it was not until April 2006 when an international team of researchers led by Eileen M. Shore PhD and Frederick Kaplan MD of the University of Pennsylvania identified he genetic mutation that causes the disease. This initial research and the resultant breakthrough were made possible by Andy Sando who, upon his death at age 44, became the first person with FOP to donate stem cells to medical research.
For those of you who have a better understanding of genetics than we do, the following is a brief explanation of what was discovered. “The team found that FOP is caused by a mutation of a gene on chromosome 2… for a receptor in the [Bone Morphogenetic Protein (BMP)] signalling pathway called ACVR1. Bone morphogenetic proteins are regulatory proteins important in embryonic skeletal formation and in post-natal repair of the skeleton. The gene identified as the FOP gene encodes a BMP receptor called Activin Receptor Type IA, or ACVR1, one of four known BMP Type I receptors. BMP receptors, located at the cell surface, help determine the fate of the stem cells in which they are expressed by transmitting signals into the cell. The classic clinical FOP presentation is caused by the specific substitution of a particular amino acid (arginine, at position 206) in the ACVR1 protein for another amino acid (histidine). This amino acid substitution induces activation of signalling by the ACVR1 receptor.”
With a newfound understanding, scientists at last had an opportunity to begin working on a potential cure. So, is there one? Unfortunately, like so many of the diseases that we have covered, the answer is a heart-breaking “not yet”. Although medical professionals now know exactly what causes this disease, a cure is yet to be found. However, progress in managing the symptoms has been made. At present, the only drug that doctors can provide to patients is Prednisone, and according to Betsy Bogard, Director of Global Research Development for the International FOP Association “It’s not proven to do anything. It just helps them feel better through the pain of a flare-up”. While this is undoubtedly a plus, it falls far short of being a cure.
One of the companies that does claim to be making advances in the search is Regeneron Pharmaceuticals in the US. According to a report, the research team have “focussed on the function of activin A, and developed an antibody that blocks its signalling pathways. When tested on mice that were genetically engineered to have the disease, the antibody was able to halt excess bone formation for up to six weeks at a time.”. Although this sounds rather promising, it is important to note that this treatment has only proved effective on mice and many previous successful medical tests for a variety of conditions have proven to be disastrous failures when replicated in humans. In spite of this, specialists remain cautiously optimistic and Regeneron say that they are committed to continuing this research. Frustratingly for sufferers of FOP, as for anybody who is suffering from an extremely rare condition, progress is slow and this is due to a variety of factors, ranging from simple awareness through to funding and the availability test subjects.
Due in large part to two organisations, awareness is slowly spreading. One of these, the International FOP Association (IFOPA) was set up by Jeannie Peeper in 1988 because she wanted to meet others with the condition, having never actually come into contact with another person who had FOP before. The website notes that “This isolation was typical before the IFOPA was formed, and Jeannie’s goal was to bring people with FOP together. Today, the IFOPA is the umbrella organization for people with FOP worldwide and the place for FOP families to come for advocacy, education and support.”. Organisations such as this, combined with the awesome power of connectivity that the Internet provides, does at least mean that the estimated 800 to 1000 people worldwide who suffer from this incredibly hard-to-manage and ultimately life-limiting condition no longer need to do so alone.