Fibrodysplasia Ossificans Progressiva (FOP)

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

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…

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

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

“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)

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

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

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

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

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)

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

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

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

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

References http://www.chinadaily.com.cn/world/2006-04/24/content_574689.htm http://www.phreeque.com/harry_eastlack.html http://en.wikipedia.org/wiki/Fibrodysplasia_Ossificans_Progressiva http://www.ifopa.org/symptoms.html http://rarediseases.about.com/cs/fop http://www.ncbi.nlm.nih.gov/omim/