Guidebook Home

Table of Contents

Preface

Introductory Comments

General Questions About FOP

Genetics of FOP

How FOP Affects the Body

Care and Treatment

Activities

Feelings About FOP

Helpful Addresses

Family Resources

Ideas for Independence

Medical Articles

Acknowledgments and Contributions

General Questions about FOP

What is FOP?
Fibrodysplasia Ossificans Progressiva (FOP) is a rare genetic condition in which the body makes extra bones in locations where bone should not form. Extra bone develops inside muscles, tendons, ligaments, and other connective tissues. This "out-of-place extra bone formation" is commonly referred to as heterotopic ossification. In people with FOP, bridges of extra bone form across the joints and lead to stiffness, locking, and permanent immobility. The condition often begins in the neck and shoulders and progresses along the back, trunk, and limbs of the body. In addition, malformed big toes (short, bent, and sometimes curved inward) are nearly always associated with the condition and can be observed at birth. While malformed big toes cause few problems, they serve as an important early sign of FOP before the onset of heterotopic ossification.

Although FOP is congenital, meaning that FOP starts before birth, the extra bone does not form at that point. Symptoms of FOP usually begin during the first two decades of life; the majority of affected people learn that they have FOP before the age of ten. Inflamed (and sometimes painful) swellings, typically in the shoulder and back areas, are usually the first sign of FOP. The swellings eventually clear up, but they leave behind an area of mature bone. People who have FOP experience different rates of new bone formation; in some the progress is rapid, while in others it is more gradual. In each case, the exact rate of progression is unpredictable although there appears to be a pattern to the progression. For example, extra bone formation tends to occur in the neck, shoulders, and upper back early in life and in the hips and knees during adolescence or early adulthood.

What does FOP stand for? When was it first documented?
FOP or Fibrodysplasia Ossificans Progressiva (Fibro-dis-playsha Os-sih-fih-cans Pro-gress-eva) means "soft connective tissue that progressively turns to bone." The earliest documented cases date back to the 17th and 18th centuries. In 1692, French physician Guy Patin met with a patient who had FOP and mentioned the encounter in his writings. In 1740, British physician John Freke of London, England, described at length to the Royal Society of Physicians an adolescent whose diagnosis included swellings throughout his torso:

After some time, the disease became known as myositis ossificans progressiva, which means that "muscle tissue turns progressively to bone." The name was modified in the 1970s (by Dr. Victor McKusick of Johns Hopkins University School of Medicine) to fibrodysplasia ossificans progressiva to acknowledge that other soft (or fibrous) tissues in addition to muscle (such as tendons and ligaments) also turn to bone.

How many people have FOP?
It is estimated that FOP affects about 2,500 people worldwide, or approximately one in two million people. Such statistics may be better grasped by the following example: if a large football stadium holds 100,000 fans, one would need to fill nearly 20 football stadiums to find one person who has FOP. At the present time, researchers are aware of approximately 600 people throughout the world who have FOP.

How is the extra bone in FOP different from the bone of the normal skeleton?
The extra bone in FOP forms by a progressive transformation of soft tissue into cartilage and bone. This is the same process by which bone regenerates (heals) after a fracture (break) occurs and is nearly identical to the process by which bone forms normally in an embryo. The abnormality in FOP occurs not in the manner of bone formation but rather in its timing and location.

Once it is mature, the extra bone in FOP is indistinguishable from normal bone except by its abnormal location. The bone is strong, can support weight, and will respond to mechanical stress as normal bone will. In fact, if the extra bone is broken, it will respond just as a normal bone would to a break and heal normally.

Will FOP get worse? Does FOP ever stop or go away?
Unfortunately, FOP does not improve over time. The "P" in FOP stands for "Progressiva." That means that FOP will progress, or get worse, as a person ages. As FOP is part of a person's genetic make-up, people with FOP are born with the condition, even though the extra bone may not have appeared at birth. So people with FOP will not outgrow the condition. Nor can the extra bone that has been produced by FOP disappear.

The body of a person with FOP does not make extra bone all of the time; a person with FOP may go months or years without a flare-up. Nevertheless, there is always a chance that extra bone can form, either without any warning, or as a result of trauma (injury), such as a bump or a fall. There are also times when, in spite of obvious trauma, FOP does not manifest itself. It is unclear why the disease is active some times and quiet or dormant at other times.

What is the IFOPA?
The International Fibrodysplasia Ossificans Progressiva Association, or IFOPA, supports education, clinical and basic research, and communication on FOP. The IFOPA was founded in 1988 by a woman who had FOP in an effort to end the social isolation imposed by this rare, debilitating disease. Today the IFOPA reaches out to over one hundred sixty families affected by FOP in twenty-one countries.

The IFOPA publishes The FOP Connection, a quarterly newsletter for FOP families and other interested individuals. The newsletter provides information on coping with a severe and chronic disability, as well as research updates and information about IFOPA events. All members are invited to submit ideas for articles and share their own stories.

The IFOPA is served by a medical advisory panel which collaborates on clinical care of FOP patients and research devoted to finding the cause of FOP and developing effective treatments for the disorder.

Visit the IFOPA home page for more information.

What is The Betty Anne Laue/IFOPA Resource Center?
In addition to being commited to FOP research, the IFOPA recognizes the importance of FOP education. Because of the disease's rarity, much misinformation still exists. To help educate families, physicians, and other interested individuals, the IFOPA operates The Betty Anne Laue/IFOPA Resource Center, a library where families and physicians can turn for information about FOP. Contact the IFOPA for more information about available resources.

What research is on-going?
Frederick Kaplan, M.D., Chief of the Division of Metabolic Bone Diseases and Molecular Orthopaedics at the University of Pennsylvania Medical Center, and Michael Zasloff, M.D., Ph.D., Adjunct Professor, Human Genetics and Molecular Biology at the University of Pennsylvania School of Medicine, serve the IFOPA as medical and scientific advisors, respectively. 1n 1989, they established the FOP Collaborative Research Project in an effort to share ideas with scientists and physicians worldwide. In 1992, their commitment helped to form a laboratory which is exclusively devoted to the research of FOP and related disorders. This unique laboratory is located in the Department of Orthopaedics of the University of Pennsylvania School of Medicine. Eileen Shore, Ph.D., who works with Drs. Kaplan and Zasloff, is the director of this molecular biology laboratory.

The FOP Collaborative Research Project is an international group of physicians, scientists, and medical student-fellows who work together on all clinical and basic science aspects of the FOP project. The international working group is dedicated to finding the cause and establishing a cure for FOP. The University of Pennsylvania Research Group has established collaborative basic and clinical research efforts with physicians and scientists throughout the world. In 1995, the group was awarded a research grant from the National Institutes of Health (NIH) to study the molecular basis of FOP. They have also been awarded an Orthopaedic Research and Educational Foundation grant to investigate transgenic animal models related to the disorder.

Scientists are studying bone morphogenetic proteins (BMPs) which they have recently identified in this disease condition. BMPs are proteins which are needed for the formation of the skeleton. Investigators have recently discovered that one of these proteins, BMP-4, a master protein for formation of the skeleton, is over-produced in a certain type of blood cell in patients who have FOP. These findings were recently published in The New England Journal of Medicine. Investigators are attempting to determine the ultimate genetic switch in FOP that leads to the formation of an extra skeleton. This may plausibly be the gene that turns on the BMP-4 gene or one that regulates its metabolism. Investigators have also recently identified the overproduction of a powerful protein that stimulates new blood vessels during times of FOP flare-ups. This powerful protein is circulated in the blood and is excreted in the urine during times of disease flare-up. The potential relationship of this protein to bone morphogenetic protein is being examined closely. Blood vessels are required for bone formation, and if new blood vessels can be arrested in the new FOP lesions, then it is possible that extra bone formation could be stopped. Investigators are currently working to develop two new drugs for treatment of FOP. One of these drugs is designed to directly inhibit the activity of BMP-4; the other is designed to inhibit the extra blood vessels that are formed in an FOP lesion at the time of a disease flare-up. These two new promising areas of drug threapy are currently in very preliminary stages of investigation but are based on recent detailed molecular laboratory findings from the FOP laboratory.