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

Fibrodysplasia Ossificans Progressiva (FOP):
Patterns of Progression

Frederick S. Kaplan, M.D. and Sharon L. Kantanie

Fibrodysplasia Ossificans Progressiva (FOP) is an extremely rare disease in which the body inappropriately makes extra bone in locations where it should not: in muscles, tendons, ligaments, and other connective tissues. It is a progressive disease in which the body essentially becomes locked inside of an extra skeleton. Yet this progression is not random in its appearance. Though FOP affects all patients differently -- at different times, to different degrees, and with different effects -- clear patterns emerge. Namely, FOP usually affects patients in the following manner: its development is axial to appendicular (meaning that the neck, spine, and shoulders will be affected before elbows, hips, and knees). Development is also cranial to caudal (meaning that the shoulders and elbows will be affected before the hips and knees). Finally, progression is proximal to distal. In other words, shoulders are affected before elbows and wrists, while hips are affected before knees and ankles.

This knowledge has enormous implications, both for the families living daily with the effects of FOP, and the people studying and treating this disease. As Rocke et al. noted, these newly recognized patterns allow families to plan for the needs of a child with a progressive disability. They also can serve as a "baseline to evaluate potential new therapies when conditions or patient numbers in this extremely rare disease do not permit the use of a true randomization, controlled trial" (Rocke et al.).

This pattern of progression, first proposed by Kaplan et al. in 1990, was confirmed in a study of 44 of 60 (73%) members of the International Fibrodysplasia Ossificans Progressiva Association (IFOPA). Various age groups were represented; two participants were under the age of 5, five were between the ages of 5 and 9, six were between the ages of 10 and 19, nine were between the ages of 20 and 29, fifteen were between the ages of 30 and 39, five were between the ages of 40 and 49, and two were over 50. The average age of participants was 27 (range 3-69). Eighteen participants were male and twenty-six were female (40% male, 60% female). Each participant was provided with an anatomical chart identifying 15 commonly involved sites and asked to identify areas in which they were affected, as well as patient age at onset. Onset of ossification (bone growth) was considered to be the time that pain/swelling first appeared.

The average age at which FOP first appeared was 5 (range birth-25). Four participants were affected at birth and eighteen (41%) were affected by age 2. By the age of seven, 80% were affected. By the age of fifteen, 95% reported onset of FOP. These findings with the assertion that FOP first manifests itself in the first decade of life.

The most common sites of early heterotopic ossification were the neck (26 people or 59%), spine (20 people or 45%), and shoulders (20 people or 45%). The percentages total more than 100 because 61% of participants reported initial and simultaneous onset at more than one site. For instance, 12 participants (27%) reported that onset occurred concurrently in all three areas. Only 5 participants (11%) reported the initial appearance of FOP at locations other than the neck, spine, and shoulders. One participant report ed initial onset at the elbow/wrist. Two cited the knee, and two others cited the hip. There was no measured difference by sex. On average, severe involvement of the lower limbs followed around a decade later.

The mean age at which specific sites were affected, based on the results of these 44 patients, is as follows (in years): neck 6 years +/- 6, spine 6 years +/- 5, shoulder 7 years +/- 6, hip 13 years +/- 8, elbow 13 years +/- 10, knee 16 years +/- 9, wrist 16 years +/- 8, ankles 17 years +/- 10, and jaw 18 years +/- 8. Interestingly, males (mean/average 10 years) reported onset of ossification at the hips earlier than female participants (mean 15 years). Data also show that the risk of heterotopic ossification remains constant with age in the neck, spine, shoulders, elbows, and ankles. Areas of increasing risk with age are jaws, wrists, hips, and knees.

These findings, that FOP follows a particular pattern of progression, could be coincidental, but more likely the genetics of FOP involve a gene-regulating pattern. Cohen et al. concluded that given our knowledge that bone morphogenetic proteins, the proteins intimately involved in the development of bone, are also associated with the process of bone formation in FOP, it is possible that candidate genes for FOP may be those that encode bone morphogenetic proteins (Cohen et al.).

Works Cited or Consulted

Cohen, Randolph B. et al. The Natural History of Heterotopic Ossification in Patients who have Fibrodysplasia Ossificans Progressiva: A Study of Forty-Four Patients. J. Bone and Joint Surgery, 75-A (2): 215-219, 1993.

Kaplan, F.S. et al. Fibrodysplasia Ossificans Progressiva: A Clue from the Fly? Calcif. Tissue Internat, 47: 117-125, 1990.

Rocke, David M., Ph.D et al. Age-and Joint-Specific Risk of Initial Heterotopic Ossification in Patients Who Have Fibrodysplasia Ossificans Progressiva. Clin. Orthopaedics, 301: 243-248, 1994.