1. Fibrodysplasia Ossificans Progressiva (FOP)

2. What Is Fibrodysplasia Ossificans Progressiva?
It is among the rarest genetic disorders
Approximately 1 case in 2 million people worldwide
The afflicted have a life expectancy of only 40 years
Fatal outcome is imminent as there is no cure
Studies are based on a few reported cases
There are no more than 2,500 cases described worldwide

3. More About FOP
The disease involves connective tissue and is caused by a defect in the repair process/mechanism
In the case of the disease, damaged normal tissue is substituted with bone tissue, causing:
Tumor like swelling…
Locking of the joints…
Restricted mobility…
Paralysis…
Death…

4. First Signs of the Disease
Patients with FOP are born with malformed curves in their big toes
This is a main characteristic which helps to distinguish FOP from other
musculo-skeletal disorders
Short thumbs are observed
In some cases…
Other skeletal abnormalities

5. Progressive Impact of the Disease
There is an increasing loss of mobility as ossification occurs
Over time, walking, eating or breathing becomes impossible
Commonly, mobility is lost by the age of 30
Terminally, ossification causes paralysis of the diaphragm, resulting in asphyxiation
Commonly, death occurs by the age of 40

6. “A Monumental Milestone”
Frederick S. Kaplan, M.D. and Eileen Shore, Ph.D. from The University of Pennsylvania, Department of Orthopedics
Found a disease causing a mutation of the ACVR1 gene on the long arm of human chromosome 2 (q23-24)
ACVR1 encodes a protein called Activin Receptor Type 1A (ACT1A)

7. Activin Receptor Type 1A
ACT1A is a bone morphogenetic protein (BMP) type receptor
It is found in skeletal muscle and cartilage tissue
The receptor protein controls the growth and development of bone and muscle
Including the transformation of cartilage into bone (ossification) during normal maturation from birth to young adulthood

8. Altered Activin Receptor Type 1A
The shape (conformation) of the mutated receptor is altered, preventing the attachment and detachment of molecules controlling the normal activity of the receptor
Thus, the receptor stays activated, constantly signaling (constitutive)
The consequence: an overgrowth of bone and cartilage, leading to joint fusion

9. Possible Treatment Approaches
Block the expression of the renegade mutant protein (from the gene)
Prevent the signal transduction pathway
Further research is necessary

10. Inheritance
The ACVR1 gene is inherited in an autosomal dominant pattern
The gene is variably expressed but is completely penetrant
It is an autosomal disorder
Most cases result from spontaneous mutations of the gene in the gametes
Many patients cannot have children due to infertility or are advised against

11. The Benefits of Research
Finding the ACVR1 gene has contributed to furthering the understanding of:
Osteoporosis (fragile bones)
Osteoarthritis (bone overgrowth)
Limb defects
…and other bone related issues such as:
Inflicted injury (Failure of a fracture to heal)
Or necessary surgery (Spinal or Cranial)

12. Special Precautions Those suffering from the disease should:
Avoid Engaging In Physical Activity
Avoid Falling Or Getting Bruised
Avoid Punctures On The Body (i.e. IV, Piercings)
Be Careful While Stretching The Joints
The above precautions do not guarantee the absence of bone growth since it spontaneously occurs

13. The Most Well Known Case
Harry Eastlack, born November 1930, died November 1973 (Pneumonia)
His body was completely ossified; he was only able to move his lips
He donated his body to science to find a cure
His skeleton Is preserved at the Mutter Museum In Philadelphia

14. WWW.IFOPA.ORG The International FOP Association
Founded by Jeanne Peeper on June 8, 1988
The association participates and
promotes research in the field
The association also provides
support to the afflicted

15. “X-tra Skeletal Bones”
Dreadful Outcome Of This Disease

16. References