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

Malformed big toes,

valgus deviation

FOP Flare-up

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/
conditions/fibrodysplasia_ossificans_
progressiva/
http://www.omim.org/entry/135100
http://www.orpha.net/consor/cgi-bi
n/OC_Exp.php?Expert=337
http://ghr.nlm.nih.gov/condition/fibro
dysplasia-ossificans-progressiva