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Presentation on Fibrodysplasia Ossificans Progressiva
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Fibrodysplasia Ossificans Progressiva (FOP)
By: Catherine Yang
What is it?
• One of the rarest, most debilitating genetic disorders known to medicine.
• Previously known as Myositis Ossificans Progressiva• Affects connective tissue.• Said to occur in approximately 1 in 2 million people
worldwide.• About 700 cases reported, 285 of those cases being
in the US.• Most patients are initially misdiagnosed
Characteristics of the disease
• People with FOP are generally born with malformed big toes.
• Affected individuals may also have short thumbs and other skeletal abnormalities.
• Have “flare-ups” that look like tumors.– “Flare-ups” appear rapidly, usually overnight– Leads to ossification
FOP Flare-upMalformed big toes, valgus deviation
Characteristics (cont)
• Flare-ups may be:– Spontaneous• Overnight, within hours
– Triggered by trauma• Falls, injections, biopsies, surgery, viral infection, etc.
• Surgical removal of FOP bone causes rapid regrowth of bone.
• Biopsies not recommended
Progression of FOP
• FOP affects– Voluntary muscle– Tendons– Ligaments– Sheet of fibrous tissue• Fasciae
Progression of FOP (Cont)
• FOP spares– Diaphragm– Tongue, but not throat– Small muscles of the hand– Cardiac and smooth muscle– Extra-ocular muscle
• Muscles that control the movement of the eye
• Progression– From the head to the bottom of the body– Axial to peripheral
What causes it?
• Caused by mutation in the ACVR1 gene.– ACVR1 gene provides instructions for production of bone
morphogenetic protein (BMP) type I receptor.• BMP helps with bone formation and maintenance
– ACVR1 protein found in many tissues of the body• Skeletal muscle, cartilage, etc.
– Helps control growth and development of bones and muscles, including the ossification of cartilage from birth to young adulthood.
• A mutation to the gene causes the receptor to be constantly turned on.– Constant activation of the receptor causes overgrowth of bone and
cartilage as well as the fusion of joints.
How is it inherited?
• Autosomal dominant pattern– Only one copy of mutated gene is sufficient to
cause the disorder• Most cases of FOP caused by new mutations in
the gene.– Only 7 families know in the world to have
multigenerational FOP
What does it do?
• Causes muscle tissue and connective tissue to ossify outside the skeleton (extra-skeletal)– Restricts movement
• Extra-skeletal bone causes progressive loss of mobility– Inability to fully open the mouth may cause difficulty eating and
speaking– Patients with FOP may experience malnutrition due to difficulties
with eating• May have difficulties with breathing
– Result of extra bone formation around ribcage that restricts expansion of lungs
– Ribcage and spinal cord fuse together
What does it do (cont.)
• Patients with FOP may need assistance for basic personal functions due to the immobility in their arms– Bathroom, eating, dressing, etc.
• Shortened lifespan– Median lifespan of 40 years– Age range of 3-77 years– Main cause of death: Cardio-respiratory failure
(54%)
Why is it hard to find?
• Normal– Biopsies look normal
under the microscope– Contents are normal
biochemically– Metabolically, the
processes are normal– Its physical contents
appear normal– It appears normal on
x-ray
• Abnormal• Bone growth
appears at the wrong time
• Bones grow in the wrong places
Common misdiagnoses
• Many patients with FOP receive an initial misdiagnosis, which leads to inappropriate medical interventions
• Common misdiagnoses include:– Cancer, Lymphoma– Fibromatosis– Injury from overuse
Diagnosis is easy!
• FOP is actually very easy to diagnose• Look for the two clinical features of the
disease:– Malformed big toes– Tumor-like lesions
• Malformed big toes + Tumor-like lesions = FOP
Treatment
• No effective treatment• Disease can be managed– Avoid trauma– Drugs being developed to control bone growth– Medications available to help relieve symptoms of
FOP such as pain and inflammation– Use muscle relaxants
Bibliography
• https://www.ifopa.org/fop-fact-sheet.html• https://www.ucsfbenioffchildrens.org/conditi
ons/fibrodysplasia_ossificans_progressiva/• http://www.omim.org/entry/135100• http://www.orpha.net/consor/cgi-bin/OC_Exp
.php?Expert=337• http://ghr.nlm.nih.gov/condition/fibrodysplasi
a-ossificans-progressiva• https://www.youtube.com/watch?v=g7dFm2
PH2TE – University of California professor on FOP
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