Osteogenesis Imperfecta - PowerPoint PPT Presentation


PPT – Osteogenesis Imperfecta PowerPoint presentation | free to view - id: 35eb6-MmI5Z


The Adobe Flash plugin is needed to view this content

Get the plugin now

View by Category
About This Presentation

Osteogenesis Imperfecta


– PowerPoint PPT presentation

Number of Views:4803
Avg rating:3.0/5.0
Slides: 45
Provided by: UNC52


Write a Comment
User Comments (0)
Transcript and Presenter's Notes

Title: Osteogenesis Imperfecta

Osteogenesis Imperfecta
  • Kaitlin
  • Ali
  • Michael

What is Osteogenesis Imperfecta?
  • Osteo-bone Genesis- creation Imperfecta-
  • A disease most commonly caused by a mutation to
    the COL1A1 and COL1A2 genes.
  • It is both a dominant and recessive disorder,
    however between 85 and 90 percent of O.I. cases
    are dominant.

What were your favorite Childhood Activities?
How common is OI?
  • Between twenty and forty thousand cases are found
    nationwide, that means 6-7 in every 100,000
  • Half of the worlds OI cases are found in the
    United States.

Diagnosis of OI
  • Fractures occurring with little or no trauma
  • Short stature or stature shorter than predicted
  • Bone Deformity
  • Blue Schlera
  • Progressive, post-pubertal hearing loss.
  • Family History

Symptoms of Osteogenesis Imperfecta
  • Muscle Fatigue.
  • Scoliosis (Curvature of the Spine).
  • Curved Limbs.
  • Blue or Gray Tint in the Whites (sclera) of the
  • May develop hearing loss later in adulthood (Can
    be as early as 20s or 30s). This is linked to
    deformities in the inner ear and three small
    bones in the middle ear.
  • Brittle and underdeveloped teeth.
  • OI patients often bruise easily.
  • Constipation.
  • Heart Defects.
  • Delays in motor development.

Treatment Options
  • There are medicines such as Bisphosphonates
    (BPs), particularly those containing nitrogen,
    that are being increasingly administered to
    increase bone mass and reduce the incidence of
  • Proper vitamin intake such as Calcium, Vitamin C,
    and Vitamin D are essential for bone growth and
  • Growth hormones and gene, cell, and drug
    therapies are also being studied.

Recent Advances in OI Care
  • They are testing different bisphospates
    pamidronate is one. I was part of an
    international study comparing Vometa to
    pamidronate, to see if it was as good or better.
    Thats about it. Eventually people would like to
    do gene therapy, but that will probably be
    decades away! Some people have done bone marrow
    transplants, but that hasnt been successful. The
    hope was that stemcells would be used to make
    normal bone. This was done at St. Jude.
  • -- Dr. Charles McKay M.D.

  • Rods are added in order to strengthen bones.
  • These rods are either non-expandable or
    expandable. Non-expandable rods are very
    versatile but must be changed as the child grows.
    Expandable rods grow with the bone, but are only
    suitable for larger bones such as the femur.
  • Spinal rodding is used in severe cases of
  • Surgery is also used in order to mend the broken

  • Normal casts would actually harm patients with
  • Instead specialized casts are used due to the
    brittle nature of the bones.
  • Fiberglass offers a lighter and more comfortable
    solution for OI patients.
  • The main purpose of casts is to immobilize the
    broken limbs. However immobilization should be
    limited in order to prevent bone loss.
  • For less serious breaks, parents are also taught
    to wrap bones for their children.

What do parents use to wrap the limbs of children
with OI?
  • They use bandages similar to Ace Bandages, they
    have special bandages for children with OI.
  • -- Dr. Charles McKay M.D.

  • Traction is used to regain alignment of a
    fracture by applying force to the body part. It
    also can relieve muscle spasms while the bone is
    healing. Skeletal traction is applied directly to
    the bones using pins, wires, or screws.

Exercise and Physical Therapy
  • Regular exercise helps the patients to become
    stronger and more independent.
  • Swimming and water exercise is the best way for
    OI patients to become more fit because it causes
    less stress on bones than any other sport.

How can children get exercise and stay healthy
with such weak bones?
  • A lot of these kids get physical therapy, and one
    of the most valuable therapies is aqua therapy.
    Their legs cannot support them, but if they get
    into the pools they can exercise their muscles
    without putting stress on their broken bones.
  • -- Dr. Charles McKay M.D.

Types of O I
  • There are 8 types of Osteogenesis Imperfecta.
  • Types 1-5 caused by Dominant Mutation
  • Type 1 is the mildest form of the disease and is
    also the most common.
  • Type 2 is fatal and usually leads to death in the
    first year of life.
  • Type 3 is the most severe form of OI found in the
    living. Those affected have a shortened life
    expectancy and necessity for a wheelchair.
  • Type 4 is moderately severe and leads to normal
    life expectancy and causes a necessity for
    crutches or braces.
  • Types 6-8 are due to recessive mutations.

What causes a child to die of type II OI?
  • The bones are just too fragile, the lungs just
    cant develop, and the child cannot breathe.
    This is due to small thorax and fractured ribs or
    flayl chest (when the child breathes, they have
    negative pressure in their chests and the chest
    collapses). A child who survives the first day
    of life may not be able to take in sufficient
    calories to survive any longer.
  • --Dr. Charles McKay M.D.

Fig 1--Life expectancy in osteogenesis imperfecta
() in comparison with that in the general
population (O). Vertical ratios determined with
the GLIM statistical package5 bars represent 95
confidence intervals for mortality
Paterson, C. R et al. BMJ 1996312351
How many patients have you seen that have died
from their Osteogenesis Imperfecta?
  • None, I have never had someone die of the
    disease. However, I have had children die of
    complications. The most common cause of death is
    from severe scholosis, the childs chest cant
    expand anymore and they may have pneumonia and
    their heart and lungs just cant expand properly.
    Another cause of death is Basilar invagination,
    which is, as the head fits on the spinal chord,
    it pushes up into the base of the brain because
    the skull is so soft.

General Health Concerns
  • Maintaining a healthy weight reduces stress on
  • Proper nutrition can be figured for OI patients
    small frames.
  • Avoiding smoking, caffine, and alcohol intake, is
    beneficial for OI patients because these lead to
    depleted bones. Taking medicinal steroids can
    also be beneficial.

This sling helps families with children who have
OI to lift and move their children. It is
specialized with those who have brittle bones.
Living With Osteogenesis Imperfecta
  • Patients must make frequent trips to the hospital
    to get casts for their multiple broken bones.
  • Braces, walkers and wheelchair use is common.
  • A balanced healthy diet and exercise is important
    to keep the fragile body as healthy as possible.
  • Specialized dental care may be necessary to
    protect fragile teeth.

Broken Bones
  • Fractured bones are a result of a gene defect
    which affects the creation of collagen, a protein
    which is needed for proper bone growth.
  • In the more mild cases of OI bone fracture
    incidence decreases after puberty.
  • However, even for the mildest form of OI (Type
    1), an average of 40 bones break prior to puberty.

Testing Options
  • 5 mL of blood in an anticoagulated tube or 5 mL
    of amniotic fluid are required for testing.
  • Skin Tests measure the collagen levels in skin
    (This technique identifies 90 of OI patients)
  • It can identify 87 of nonfatal OI and 98 of
    fatal OI.
  • Chronic Villus sampling can be used to detect
    abnormal collagen and genetic mutations.
  • Amniocentesis can also analyze for genetic
  • Prenatal testing is suggested for families that
    have a member who has already been diagnosed.

Cost of Testing
  • Collagen TestingResults in 6-8 weeks770.00 -
  • DNA SequencingResults in 6 months2,363.00 for
    both genes

Testing Ethics
  • Testing in Parents can help determine the
    prognosis of having another child affected by OI.
    This is most commonly done in mothers who have
    lost a child to OI.
  • Tests are not 100 percent effective due to the
    fact that over 800 mutations have been identified
    so far in the COL genes
  • Genetic counseling should be used along with
    testing in order to help parents understand the
    disease, the risks, and the test.

How is genetic testing performed for patients
with OI?
  • A test would be sent to Peter Byers in Seattle,
    WA, and for genetic testing. There is another
    site in New Orleans. They used to do collagen
    testing, growing fibroblasts,(makes connective
    tissue in skin) and would be tested to see if it
    makes normal collagen. Genetic testing is new.
    COL1A1 genetic mutations cause OI. From this
    gene you are looking for abnormalities. Because
    its such a long protein, its hard to find all
    the abnormalities. Most types of OI are found in
    this gene.
  • -- Dr. Charles McKay M.D.

Why do you do genetic testing?
  • I dont do genetic testing on everyone. If Im
    sure of the diagnosis, like if the mother has OI
    or if the child has classic blue sclera or teeth.
    Genetic testing can be used to confirm a case or
    to confirm the diagnosis of a new mutation within
    a family. Its not necessarily necessary. I
    know Peter Byers, a geneticist who specializes in
    the OI genetic tests. Eventually what they would
    like to do is correlate what the defect is and
    what the clinical course would be. They want to
    see if certain courses would be more effective
    for certain defects.
  • -- Dr. Charles McKay M.D.

What does the COL1A1 Gene do?
  • The normal COL1A1 gene functions as a
    collagen-producing gene.
  • The COL1A1 gene codes for proa1(1) and proa(2)
    which both are necessary to create type I
  • When mutated, the COL1A1 gene causes the victim
    to have a reduced amount of collagen or weak,
    less effective collagen.

Gene Defects
  • Of your gene defects, if you have mild OI, you
    dont make enough collagen. If you have two gene
    defects perhaps one doesnt make enough protein.
    Typically you make two strands, and they have to
    wrap together. If you dont make enough of one
    protein, its hard to have enough collagen. In
    the more severe form, you have one normal
    collagen and one abnormal collagen, and what
    happens is the abnormal collagen will keep the
    normal collagen from functioning properly, this
    is in your type II or type III OI.
  • -- Dr. Charles McKay M.D.

COL1A1 and COL1A2 Genes
  • The COL1A1 gene is found on the seventh
    chromosome, while the COL1A2 gene is found on the
    seventeenth chromosome and are responsible for
    the creation of Type One Collagen.
  • Type 1 collagen is a peptide chain composed of 2
    alpha-1(COL1A1) chains and 1 alpha-2 (COL1A2)
    chains to be functional.

Type 1 Collagen
  • Type 1 collagen is the most abundant type of
    collagen in the human body.
  • It is found in scar tissue, tendons and the
    myofibirils (muscle cell), and in bones.

Why do we need Collagen?
  • Collagen is a fiberous protein that connects and
    supports tissues within the body.
  • Collagen is found in eyes, hair, teeth, bone,
    skin, cartledge and tendons, connective tissue,
    capillaries, the kidneys and the placenta.

Genetics of Dominant Cases of O I
  • It is not a sex-linked disorder
  • Caused by a spontaneous mutation that occurs
    prior to conception in the egg or sperm.
  • 35 of diagnosis occur in families without any
    history of the disease.

Common types of Mutationto the COL1A1 Gene
  • Point Mutation- is a type of mutation where the
    replacement of a single base nucleotide with
    another nucleotide.
  • Deletion- a type of genetic mutation occurring
    when part of a chromosome or a sequence of DNA is
  • Insertion- a genetic mutation that occurs when
    one or more nucleotide base pairs is added into a
    genetic sequence.

De Novo Mutation
  • An alteration in a gene that is present for the
    first time in one family member as a result of a
    mutation in a germ cell (egg or sperm) of one of
    the parents or in the fertilized egg itself.
  • 60 percent of patients with mild OI have this
    type of mutation
  • Almost 100 percent of babies with fatal OI have
    de novo mutation.

Life With OI
  • His world has been hospitals, labs, clinics,
    specialist and doctors offices. He takes a large
    assortment of medications, he is hooked up to the
    VNA and other support systems us, we are it and
    he has taught us so much through this.
  • James is a high functioning adult, loves people
    and we are blessed for having him, he has taught
    us not to take anything for granted, look at
    things with simplicity and love. He has an
    apartment in our building, to help him maintain
    as much independence as he can, he does quite
    well. He has days that are very difficult because
    the O.I. has affected his respiratory system and
    his heart, he has CHF. His attitude is great and
    through this the medical field has learned a lot
    about O.I. especially his primary doctor, who has
    kept on top of his situation, they have gained a
    sense of humor and this has helped James cope
    with his health.
  • They never thought he would live beyond 14,
    well he has beaten those odds. We love James and
    will always fight to make life better for him, he
    has given us more then he will ever know. He has
    such an innocence about him, he becomes

Interview with Dr. Charles McKay
  • Dr. McKay is a local Osteogenesis Imperfecta
    specialist who works at Carolinas Medical Center
    in Charlotte, NC. He began his OI clinic there
    in 2006, after joining the CMC faculty as a
    Nephrologist. He started this clinic because he
    saw a need for a OI specialist in the Southern
    United States. He had a clinic at his previous
    job at A.I. duPont Hospital for Children in
    Wilmington, Delaware.

I know Osteogenesis Imperfecta is a rare disease.
How did you learn about it?
  • Initially I learned about it reading about bones
    and pediatrics. Then about osteoporosis. At
    duPont, they needed someone to treat children
    with pamidronate.

Why did you chose to learn more and eventually
care for children with osteogenesis imperfecta?
  • I read about it. I read the facts and I
    understood it. Then I suddenly started seeing
    patients and needed to know much more. What I
    needed to know to care for patients was a great
    deal more. It went from a casual knowledge to
    being an expert in order to care for patients. I
    learned a lot reading and from parents taking
    care of their children each day, the problems
    they had and what works and what doesnt. Some
    of the parents have O.I. as well.

What is it like to take care of children with OI?
  • Its very rewarding because you have to remember
    some have a very mild disease and some have a
    very severe disease, so its a very different
    experience. Some children just have fractures
    and need medication, but some children are
    remarkable, being able to live a relatively
    normal life and being able to do what ever child
    wants to do. As the OI foundations says, these
    children have unbrakeable spirits. There are
    also children who will never walk, will always be
    in a wheelchair, but still can have a wonderful
    sense of self. And they have their own
    aspirations. Many want to do something with
    computers because it is something they can do
    still being crippled.

What is it like to take care of children with OI?
  • Its very rewarding because you have to remember
    some have a very mild disease and some have a
    very severe disease, so its a very different
    experience. Some children just have fractures
    and need medication, but some children are
    remarkable, being able to live a relatively
    normal life and being able to do what ever child
    wants to do. As the OI foundations says, these
    children have unbrakeable spirits. There are
    also children who will never walk, will always be
    in a wheelchair, but still can have a wonderful
    sense of self. And they have their own
    aspirations. Many want to do something with
    computers because it is something they can do
    still being crippled.

What special considerations do you have to take
to properly care for children with OI?
  • They are at risk for fractures, so you have to be
    careful handling the child. I once even
    accidentally broke a childs arm. I picked her
    up to move her, and put too much pressure on her.
    You have to be careful not to put pressure on
    them. You cant pick them up by their arms, like
    you would a normal child, because their bones are
    fragile. That was a pretty terrible experience.
    I dont know if I actually broke her arm, but she
    developed pain. These children may need special
    dental care or have constipation. They may need
    special aids to exercise. For some kids, they
    start fracturing when they start walking. This
    is when you often need to rod their bones. They
    can develop deafness, so they may need to be
    checked for that. They can also get
    hydrocephilis (swelling of the ventricles in the
    brain). Just because the child has fractures and
    maybe wheelchair bound, doesnt mean they dont
    have dignity. To treat them like real people is
    very important.

Do you have an recommendations to give to
parents with affected children?
  • When I see them for the first time, I try to
    first figure out how severe the OI is and how
    likely they are to get fractures. Some have
    already had many fractures, and may need to or
    may be seen by an orthopedic specialist. After I
    treat them with pamidronate, we encourage parents
    to allow them to be children, knowing that they
    may get a broken bone, but we still want them to
    play and be children. When they do get a broken
    bone, parents are taught not to bring their
    children to an emergency room to get a cast, but
    to wrap it, putting it in a splint. This allows
    it to heal. Casts are more likely to break

Do you have and special anecdotes that you would
like to share about a patient?
  • Well, Ive had patients in wheelchairs that were
    able to walk. One thing about patients with OI is
    that they may have different forms of getting
    around due to distance and how many people will
    be around. Some patients use special wheelchairs
    that can even lift them up. Its miraculous to
    have children with parents who have severe OI and
    have been able to have children. Some people
    with OI are only about sixty pounds.

But, there is hope!
  • Doctors, including endocrinologist Dr. Orwoll, is
    experimenting with a medicine called Forteo,
    meant to treat patients with osteoporosis."In
    osteoporosis, Forteo does work by forming new
    bone and strengthens the bone and reduces
    fracture," Dr. Orwoll says. This medicine has
    also been used to help strengthen the bones of
    patients with mild Osteogenesis Imperfecta, and
    has given patients hope for a more normal life!
  • Life With OI
About PowerShow.com