So, What's the Point?

So, why choose O.I. for my presentation?

I was going to do it on American Sign Language, because I am so interested in it and want to learn it after I graduate. But then I looked through the example binder of O.I., and realized I had to change my topic. I know a family who has dealt with this for the length of their oldest son's life, and I have watched it for that whole time. It has always broken our hearts when we heard about another fracture or flying out to Omaha for another surgery, being in another wheelchair, etc. Their interview is below, here.

I also realized, even though we've watched this boy's experience, I had NO idea what O.I. actually was! I began the basic research, and realized that I had no idea what it actually meant. Now I'm on a roll, and it's become almost an obsession to find out as much as I can about this disease. I have the attitude of wanting to fix something that hurts people that I love, and this is no different. I want to continue my research, even after this project, to find out all the information on fighting this disease that I can.

What IS O.I.?

What is O.I.?

http://www.mdjunction.com/osteogenesis-imperfecta/videos
Definition
Osteogenesis imperfecta (O.I.) is a genetic disorder characterized by bones that break easily, often from little or no apparent cause. A classification system of different types of O.I. is commonly used to help describe how severely a person with O.I. is affected. For example, a person may have just a few or as many as several hundred fractures in a lifetime.

Prevalence
While the number of people affected with O.I. in the United States is unknown, the best estimate suggests a minimum of 20,000 and possibly as many as 50,000.

Diagnosis
O.I. is caused by genetic defects that affect the body’s ability to make strong bones. In dominant (classical) O.I., a person has too little type I collagen or a poor quality of type I collagen due to a mutation in one of the type I collagen genes. Collagen is the major protein of the body’s connective tissue. It is part of the framework that bones are formed around. In recessive O.I., mutations in other genes interfere with collagen production. The result in all cases is fragile bones that break easily.

It is often, though not always, possible to diagnose O.I. based solely on clinical features. Clinical geneticists can also perform biochemical (collagen) or molecular (DNA) tests that can help confirm a diagnosis of O.I. in some situations. These tests generally require several weeks before results are known. Both the collagen biopsy test and DNA test are thought to detect almost 90% of all type I collagen mutations. 

A positive type I collagen study confirms the diagnosis of dominant O.I., but a negative result could mean that either a collagen type I mutation is present but was not detected or the patient has a form of the disorder that is not associated with type 1 collagen mutations or the patient has a recessive form of O.I. Therefore, a negative type I collagen study does not rule out O.I. When a type I collagen mutation is not found, other DNA tests to check for recessive forms are available.

Inheritance Factors
Most cases of O.I. (85-90%) are caused by a dominant genetic defect. This means that only one copy of the mutation carrying gene is necessary for the child to have O.I. Children who have the dominant form of O.I. have either inherited it from a parent or, when the parent does not have O.I., as a spontaneous mutation.

Approximately 10-15 percent of cases of O.I. are the result of a recessive mutation. In this situation, the parents do not have O.I., but both carry the mutation in their genes. To inherit recessive O.I. the child must receive a copy of the mutation from both parents.

When a child has recessive O.I., there is a 25 percent chance per pregnancy that the parents will have another child with O.I. Siblings of a person with a recessive form of OI have a 50 percent chance of being a carrier of the recessive gene. DNA testing is available to help parents and siblings determine if they are carriers of this type of gene mutation.

A person with a form of O.I. caused by a dominant mutation has a 50 percent chance of passing on the disorder to each of his or her children. If one parent has O.I. because of a recessive mutation, 100 percent of their children will be carriers of the recessive O.I. mutation. Whether any of these children will have O.I. will depend on their inheritance from the other parent. Genetic counselors can help people with O.I. and their family members further understand OI genetics and the possibility of recurrence, and assist in prenatal diagnosis for those who wish to exercise that option. For more information on O.I. inheritance, see the O.I. Foundation fact sheet titled “Genetics.”

What kinds of O.I. are there?

Clinical Features
The characteristic features of O.I. vary greatly from person to person, even among people with the same type of O.I., and even within the same family. Not all characteristics are evident in each case. The majority of cases of O.I. (possibly 85-90 %) are caused by a dominant mutation in a gene coding for type I collagen (Types I, II, III, and IV in the following list). Types VII and VIII are newly identified forms that are inherited in a recessive manner. The genes causing these two types have been identified. Types V and VI do not have a type 1 collagen mutation, but the genes causing them have not yet been identified. The general features of each known type of O.I. are as follows:

Type I

• Most common and mildest type of O.I.
• Bones fracture easily. Most fractures occur before puberty.
• Normal or near-normal stature.
• Loose joints and muscle weakness.
• Sclera (whites of the eyes) usually have a blue, purple, or gray tint.
•  Triangular face.
• Tendency toward spinal curvature.
• Bone deformity absent or minimal.
• Brittle teeth possible.
• Hearing loss possible, often beginning in early 20s or 30s.
• Collagen structure is normal, but the amount is less than normal.

Type II

• Most severe form.
• Frequently lethal at or shortly after birth, often due to respiratory problems. 
• Numerous fractures and severe bone deformity.
• Small stature with underdeveloped lungs.
• Tinted sclera.
• Collagen improperly formed.

Type III

• Bones fracture easily. Fractures often present at birth, and x-rays may reveal healed fractures that occurred before birth.
• Short stature.
• Sclera have a blue, purple, or gray tint.
• Loose joints and poor muscle development in arms and legs.
• Barrel-shaped rib cage.
• Triangular face. 
• Spinal curvature.
• Respiratory problems possible.
• Bone deformity, often severe.
• Brittle teeth possible.
• Hearing loss possible.
• Collagen improperly formed.

Type IV

• Between Type I and Type III in severity.
• Bones fracture easily. Most fractures occur before puberty.
• Shorter than average stature.
• Sclera are white or near-white (i.e. normal in color).
• Mild to moderate bone deformity.
• Tendency toward spinal curvature.
• Barrel-shaped rib cage.
• Triangular face.
• Brittle teeth possible.
• Hearing loss possible.
• Collagen improperly formed.

By studying the appearance of O.I. bone under the microscope, investigators noticed that some people who are clinically within the Type IV group had a distinct pattern to their bone. When they reviewed the full medical history of these people, they found that groups had other features in common. They named these groups Types V and VI O.I. The mutations causing these forms of O.I. have not been identified, but people in these two groups do not have mutations in the type I collagen genes.

Type V

• Clinically similar to Type IV in appearance and symptoms of O.I.
• A dense band seen on x-rays adjacent to the growth plate of the long bones.
• Unusually large calluses (hypertrophic calluses) at the sites of fractures or surgical procedures. (A callus is an area of new bone that is laid down at the fracture site as part of the healing process.)
• Calcification of the membrane between the radius and ulna (the bones of the forearm). This leads to restriction of forearm rotation. 
• White sclera.
• Normal teeth. 
• Bone has a “mesh-like” appearance when viewed under the microscope. 
• Dominant inheritance pattern

Type VI

• Clinically similar to Type IV in appearance and symptoms of O.I.
• The alkaline phosphatase (an enzyme linked to bone formation) activity level is slightly elevated in O.I. Type VI. This can be determined by a blood test. 
• Bone has a distinctive “fish-scale” appearance when viewed under the microscope.
• Diagnosed by bone biopsy.
• Whether this form is inherited in a dominant or recessive manner is unknown, but researchers believe the mode of inheritance is most likely recessive.
• Eight people with this type of O.I. have been identified.

Recessive Forms of OI
After years of research, two forms of O.I. that are inherited in a recessive manner were discovered in 2006. Both types are caused by genes that affect collagen formation. These forms provide information for people who have severe or moderately severe O.I. but who do not have a primary collagen mutation.

Type VII

• The first described cases resemble Type IV O.I. in many aspects of appearance and symptoms.
• In other instances the appearance and symptoms are similar to Type II lethal O.I., except infants had white sclera, a small head and a round face.
• Short stature.
• Short humerus (arm bone) and short femur (upper leg bone) 
• Coxa vera is common (the acutely angled femur head affects the hip socket).
• Results from recessive inheritance of a mutation to the CRTAP (cartilage-associated protein) gene. Partial function of CRTAP leads to moderate symptoms while total absence of CRTAP was lethal in all 4 identified cases.

Type VIII

• Resembles lethal Type II or Type III O.I. in appearance and symptoms except that infants have white sclera.
• Severe growth deficiency.
• Extreme skeletal under mineralization.

Caused by a deficiency of P3H1 (Prolyl 3-hydroxylase 1) due to a mutation to the LEPRE1 gene.

How can you treat O.I.?

Treatment
There is not yet a cure for O.I. Treatment is directed toward preventing or controlling the symptoms, maximizing independent mobility, and developing optimal bone mass and muscle strength. Care of fractures, extensive surgical and dental procedures, and physical therapy are often recommended for people with O.I. Use of wheelchairs, braces, and other mobility aids is common, particularly (although not exclusively) among people with more severe types of O.I.

People with O.I. are encouraged to exercise as much as possible to promote muscle and bone strength, which can help prevent fractures. Swimming and water therapy are common exercise choices for people with O.I., as water allows independent movement with little risk of fracture. For those who are able, walking (with or without mobility aids) is excellent exercise. People with O.I. should consult their physician and/or physical therapist to discuss appropriate and safe exercise.

Children and adults with O.I. will also benefit from maintaining a healthy weight, eating a nutritious diet, and avoiding activities such as smoking, excessive alcohol and caffeine consumption, and taking steroid medications — all of which may deplete bone and make bones more fragile. For more information on nutrition, see the O.I. Foundation fact sheet titled “Nutrition.”

A surgical procedure called “rodding” is frequently considered for people with O.I. This treatment involves inserting metal rods through the length of the long bones to strengthen them and prevent and/or correct deformities. 

This treatment is most commonly done in the legs and the arms as needed. Rodding not only corrects bowing (curving) of the bone, but also adds an internal support that helps to prevent further fractures. The age of the child on which this operation is performed depends greatly on the size of the bones, but it is frequently done on children as young as two or three years old.

When considering this option for your child, be sure to discuss the pros and cons of telescoping and nontelescoping rods with your orthopedic surgeon. Also, keep in mind that this is a treatment that must be repeated as the child outgrows the rods.

Several medications and other treatments are being explored for their potential use to treat O.I. These include growth hormone treatment, treatment with intravenous and oral drugs called bisphosphonates, an injected drug called teriparatide (for adults only) and gene therapies. It is not clear if people with recessive O.I. will respond in the same manner as people with dominant O.I. to these treatments. The O.I. Foundation provides current information on research studies, as well as information about participating in clinical trials.

Prognosis
The prognosis for a person with O.I. varies greatly depending on the number and severity of symptoms. Respiratory failure is the most frequent cause of death for people with O.I., followed by accidental trauma. Despite numerous fractures, restricted physical activity, and short stature, most adults and children with O.I. lead productive and successful lives. They attend school, develop friendships and other relationships, have careers, raise families, participate in sports and other recreational activities and are active members of their communities.

Shriner's Montreal O.I. Clinic

A list of O.I. Doctor's specialists:
http://www.oif.org/site/DocServer/2009_Clinic_Directory_final.pdf?docID=10161


http://www.oif.org/site/PageServer?pagename=Pamidronate

Support Groups

Osteogenesis Imperfecta Foundation
804 W. Diamond Avenue, Suite 210, Gaithersburg, MD 20878
Tel: 800-981-2663 or 301-947-0083
Fax: 301-947-0456
Internet: www.oif.org
E-mail: bonelink@oif.org

https://www.facebook.com/groups/43935368633/
(Osteogenesis Imperfecta Facebook Support Group)

http://www.dailystrength.org/c/Osteogenesis-Imperfecta/support-group

Videos of Patients with O.I.

Children of Glass Documentary Series:

http://www.youtube.com/watch?v=TpAMTOud3bw&feature=relmfu

 http://www.youtube.com/watch?v=GTpSxlPzC8k&feature=relmfu

 

 http://www.youtube.com/watch?v=L2f8fz6vzoI&feature=relmfu

http://www.youtube.com/watch?v=QvbY7XqyMz8&feature=relmfu

Natalie's Treatments at Hopkins Hospital:

http://www.youtube.com/watch?v=Z7d27bBwX3E

Children's Hospital Omaha O.I. Clinic

Osteogenesis Imperfecta Clinic

The Osteogenesis Imperfecta Clinic at Children's Hospital & Medical Center is recognized worldwide for its expertise and leadership in treating children with brittle bone disease, also known as osteogenesis imperfecta (OI). In years past, many children with OI faced a future filled with pain, bone fractures, surgeries, casts and immobility. However, today, thanks to advanced techniques like those used at the OI Clinic at Children's, we offer many children the opportunity to live a more active lifestyle and have hope for a brighter future. As a regional center for OI treatment, approximately 80 percent of patients travel significant distances to Omaha to seek treatment. Our goal is to increase the quality of life for these children through compassionate care, advanced medical options and continued research so that we can find a cure for this genetic disorder.
Our staff includes a team of multidisciplinary health care professionals who are trained and experienced in treating and managing children with OI. Led by medical director Richard Lutz, M.D., fellowship-trained in pediatric genetics, endocrinology and metabolism, and Paul Esposito, M.D., fellowship-trained in pediatric orthopaedic surgery, the team also includes physical and occupational therapists, an audiologist, dietitian, nurses, nurse practitioners and radiology technologists, all working in one location to make the care process more convenient and comfortable for you.

What Is Osteogenesis Imperfecta?

Osteogenesis imperfecta (OI) is a genetic disorder that primarily affects the body's ability to produce collagen found in bones and other tissues. As a result, bones are brittle and break easily. Other possible symptoms of OI include curved bones, scoliosis, muscle weakness, joint laxity, fragile skin, blue sclera, brittle teeth, breathing problems and shortness of stature. Hearing loss is also common, especially in adulthood. The symptoms and severity of OI vary greatly from mild cases that may go undetected; to moderate cases with multiple symptoms and more fragile bones; to acute cases where life expectancy may be decreased, largely as a result of respiratory failure. OI occurs in males, females and all ethnicities. Although it can be inherited, OI frequently appears in families with no previous history of the disorder. This is due to gene mutation rather than any action taken by either parent before or during pregnancy.

Treatment

Each child with OI is unique, not only as an individual but also in diagnosis. Children's OI Clinic takes a highly personalized approach to patient care. Individual treatment protocols frequently are adjusted based on pain and fracture potential, age, growth and other key factors. Physical and occupational therapies progress along with your child's development. We listen to feedback from you and your child and seek minimal treatment for maximum benefit. Since the majority of our patients travel to Omaha from many states and several countries, we interface with primary care providers and health agencies in your hometown to safely administer medication and other therapies. We also work with insurance companies to stress the role that early preventive care plays in lessening the cost of care for osteogenesis imperfecta.
At Children's OI Clinic, we strongly believe in treating significantly involved infants early to decrease bone fractures. This involves using intravenous bisphosphonate medications like pamidronate, which improves the density of bone and reduces the pain suffered by your child. (This practice differs from many practitioners who don't begin treatment until a child reaches the toddler stage.) However, research is showing that early bisphosphonate treatment leads to a better prognosis for decreased fractures and pain and improved psychomotor development, leading to increased mobility, comfort and confidence. We also have found that the earlier your child is treated, the fewer number of surgeries he or she will need and the more normal his or her growth and development will be.
Your child's bone density is measured and monitored throughout the treatment process with a Dual Energy X-ray Absortiometry, or DEXA scanning. Unlike scanners that measure bone density in adults, the high-tech DEXA scanner is gauged specifically for children, including babies and toddlers. Our radiology technologists have extensive experience in working with children and osteogenesis imperfecta. We expose the children to the least amount of radiation to obtain the maximum benefit.

Advanced Treatment

For children with moderate to severe OI, the combination of bisphosphonate treatments that strengthen bones followed by the surgical insertion of growing rods offers the greatest promise for improved comfort, growth and development. The most commonly used rods are the Fassier-Duval Telescopic Rods, which are inserted through relatively small incisions often without postoperative casting.
The Children's OI Clinic embraced the procedure early on after Dr. Esposito received training from co-inventor of the rods, Francois Fassier, M.D., of Montreal. We have since built one of the most active programs in the nation. Because of Dr. Esposito's interest in the care of these children, he is often consulted by other pediatric orthopaedic surgeons across the country.

Research

With the support of the OI Foundation, Dr. Lutz and Dr. Esposito are collaborating with other OI centers, including the Kennedy Krieger Institute at Johns Hopkins and the Shriners Hospitals for Children in Chicago and Montreal, in an effort to find a cure for OI through advanced research. While a cure is not imminent, other research being conducted at our clinic will have a more immediate impact upon treatment protocols for the disorder. Current studies involve data collected from numerous growing rod surgeries, spinal deformity studies and information regarding hearing loss in OI patients. Dr. Lutz and Dr. Esposito also are widely published and are in frequent demand as lecturers on the topic of OI. The goal of the team is to ensure that all children with OI, regardless of where they live, receive optimal care.

Interview with a Family

This is an interview with a mother of a child who is living with O.I. I have known them my entire life, so this was the reason I got into this subject for my project. Jonathan just graduated from 6th grade, and is recovering from a fracture which put him in a wheelchair.

When did you first find out Jon had OI? What was yours and Mike's reaction?

Jonathan was first diagnosed with O.I. about 10 hours after he was born. When he was born one of the nurses noticed that his cry was a painful sounding cry. Because he was breech and sitting on his legs/criss-cross and because I had very little amniotic fluid (which is what lead them to deliver Jonathan 15 days early) they decided to X-ray his lower legs to see if something was hurt/broken? The X-ray caught a part of his upper leg which they noticed had been broken and was healing. That lead to them x-raying his whole body where they found he had 7 fractures. 6 were in various states of healing and his arm was newly broken. We of course were so sad when we first found out. All the information that you first find out about O.I. is very devastating. It's a very long list of horrible things that are typically found in someone who has O.I. On one hand we were sad, because we had just been giving such a life-altering diagnosis for Jonathan, but on the other hand, we were completely in love with this new little spirit that Heavenly Father had entrusted to us. We loved him from the moment we saw him and knew we would do anything for him to help him live a happy and productive life.  The first few months were very hard. Jonathan broke 7 more bones by the time he was 4 months old. I felt so helpless. I'm a person who fixes things when there is a problem. But there was no way to fix this, or undo this. It was something we had to come to terms with. And of course there were so many unknowns at that time. No one knew if he'd be able to sit or crawl or stand or walk. He seemed to be breaking his bones from absolutely nothing...so the situation looked very grim at the beginning. Here is one of my favorite pictures of Jonathan the day he was born.

  

What type of O.I. does Jonathan have?

When he was born we were told he has type III, which is the most severe form (other than type II which is lethal at birth). This was because of the number of in-utero fractures he had when he was born. When he was 2 months old and we had our first appointment at Shriners in LA the doctor there, who had quite a bit of O.I. experience, told us that his full body X-ray looked "too good be a type III, but not good enough to be type I"...so that makes him type IV, which basically is a catch-all for everything in between type III and I. The expert doctors that we see now don't like to use the types because there is such a variance between them. I've seen type III's who rarely break and type I's who break all the time. They, and we, prefer to use "mild," "moderate," or "severe". I call Jonathan "moderate".

What kind of research did you do when you discovered that Jonathan had O.I.?

The internet was not as vast 12 years ago as it is today! But we were still able to find a good deal of info on O.I. on the internet. Much of it was depressing, but that is where we first learned about Pamidronate treatments. And because of that initial research we did we were able to start Jonathan on this medicine, which was still experimental, when he was 8 weeks old! We lived in Provo, UT at the time and the drug was only administered in Los Angeles, CA and Montreal, Canada. So we flew to LA for his first treatment. My mom, who was an absolute angel to us, contacted anyone she could find online who had a child with O.I. She would write to them and they would share letters of encouragement and support. My mom would print these off and bring them to me. They helped me feel like I wasn't alone. Our continued research led us to Shriners Hospital in Montreal where the worlds top O.I. doctors were located. We flew there when Jonathan was 3 to be evaluated. One of the doctors there eventually started an O.I. clinic in Omaha, Nebraska which is where Jonathan started going when he was 5. The care and experience we get there is amazing!

How many times have you had to bring Jon to the hospital with breaks?

Wow...I don't even know. He's had over 40 fractures. So he's had A LOT of trips to the hospital, doctors office, Omaha, etc! When Jonathan was 13 months old he had his first rodding surgery, which is were metal rods are placed inside the length of his femur bones. This made his femurs straighter, so they would break less. It also acted as an internal splint so that when he broke his femur he didn't need to have a cast. This was a huge blessing for us! Jonathan had a handful of femur fractures before he had these rods placed and a broken femur always meant a spica cast. A spica cast goes from your ribs to your toes. It's basically a half body cast and it is HORRID! However, the rods have a high complication rate and sometimes bend when his leg breaks. Jonathan has had 9 rodding surgeries in all to place or replace the rods in his legs.  Jonathan also goes to the hospital often for his Pamidronate infusions. These were every 8 weeks as a baby...and now every 4 months for a 2-3 day IV infusion. He's grown up in hospitals and has lots of wonderful nurses and doctors who have made the hospital a fun place for him...for the most part.

Has Jon needed services at school? What kinds of services?

Jonathan has had an IEP (Individualized Education Plan) since he was in preschool. Some of the services we've had are a one-on-one aide to help keep him safe at school. He has also had 2 one-hour water therapy sessions a week...which have been wonderful for him. Some things that he has in place now is an extra set of books to keep at home, permission to leave class early or late if needed to avoid the mad rush in the hallways. He has adaptive PE, meaning he can do different things if he needs to for PE...though he prefers to just do what the class is doing whenever possible.

What has your experience been with the professionals you've come in contact with?

We learned pretty early on that most doctors think they now about O.I., but really only a handful REALLY know what they are talking about. That is the main reason we fly to Omaha for Jonathan's clinic visit (a once a year major check-up) and for any surgeries he needs. The peace of mind that comes from having a skilled surgeon who works on probably more than a hundred O.I. kids versus the local doctor who has maybe seen a few cases in their entire practice of medicine. I seen far too many families who have been given misinformation by well meaning doctors that have had profoundly negative affects on their child's well being. We feel so blessed to have gotten in touch with excellent doctors early on. 

How has O.I. affected your other children?

I'm not sure...because its' such a normal part of our life. Jonathan is the oldest of 4 boys, so his brothers have grown up knowing they have to be careful around him.It's just second nature. For example we are extremely vigilant about wiping up any spills on the floor because Jonathan slipped once and broke his leg and needed surgery. So our kids just see us wiping up ANYTHING that has spilled. All of our boys, by about 18 months old, just start wiping up their own spills. It's pretty funny to see it, but they somehow just realize that's what we do in our house. I am also amazed to watch Joanthan's brothers play with him. They know how to rough house with Jonathan but also have this innate understanding of not letting things go too far. I think my boys are pretty nice kids, maybe because pounding on your brother, hitting, kicking, fighting, etc...was just never an option in our house. The boys have always treated each other pretty kindly. They are very willing to be helpful to Jonathan when he is hurt. I remember one moment that was particularly touching, Jonathan (who was 11 at the time) had broken his leg while Andrew (8 yrs) was not home. When Andrew got home and I told him that Jonathan had broken his leg he just burst into tears. I think he knew the pain and the frustration that Jonathan feels when this happens and he was feeling the same frustration for him too. My boys are great friends...whenever it's the weekend or summer they all sleep together in the same room. And of course they are all in Jonathan's room, the smallest room in the house! Because Jonathan's room is downstairs (the other boys are upstairs) as it's safer for him not to be going up and down stairs. All in all, I think it's made my boys much more aware that sometimes people have disabilities and it's just a part of life...not that big of a deal.

Resources

http://en.wikipedia.org/wiki/Osteogenesis_imperfecta
http://www.oif.org/site/PageServer?pagename=fastfacts
http://www.nlm.nih.gov/medlineplus/osteogenesisimperfecta.html
http://bones.emedtv.com/osteogenesis-imperfecta/osteogenesis-imperfecta-treatment.html
http://emedicine.medscape.com/article/1256726-treatment
www.wishboneday.com/
http://www.shrinershospitalsforchildren.org/en/Hospitals/Locations/Canada/Orthopaedics/OsteogenesisImperfecta.aspx