Osteogenisis Imperfecta, God Appointments, and Lucy Q&A

       
   The Lord comforts us in amazing ways.

    After we found out about Lucy's neck, we started looking into the Bell Center - Early Intervention program.  My mother told me about a friend of a friend who's daughter takes her little girl to the Bell Center.  (yes....I know that was hard to follow.   This is how God works.)  Anyway, the mom's name was Jenna and her daughter is Maggie.  Maggie has Osteogenisis Imperfecta.  My mom said that even though Lucy didn't have this diagnosis...we should call her and get her opinion of the Bell Center.  (In life there are no coincidences).  Jenna is an amazing person!  She made me feel so hopeful.  She praised the Bell Center and made me feel comfortable with the steps we were taking.  We talked about our daughters and shared stories.  Maggie has type II OI, which is a very severe form...often times fatal in the first year of life.  Maggie is a miracle....she actually rarely breaks!  (Before I tangent away from where I want to go with this post...I just want to say:  We are so eager to find someone to compare our children to when they are having a problem.  Its only natural, we want to know what to expect and how to best care for our child.  There may be some diagnosis's where this works....it doesn't in OI.  OI children are often called snowflakes....they are fragile, beautiful, and completely unique, even within types).  The information I want to share with you about OI is only a guideline.

   After Dr. Bober called me with Lucy's Diagnosis...guess who I called? 

   Jenna was a great resource for me and contacted another OI mom....Dana, who has a daughter Rhae with type III, to add me to the OI parents group on FB.  That group has taught me everything that I know about OI.  The group has 718 members.  Almost all of the members are parents of children with OI.  (Can I just take a moment...to talk about how God makes appointments for you.  This is His not so subtle way of telling you....I'm in control of this, Ive got this, I'm taking care of you, I haven't forgotten about you, trust me. If you don't know the Lord and you are facing an overwhelming circumstance, just take a moment now to ask Him into your heart.  You too can experience the comfort, peace, and guidance, that only comes from my Savior, Jesus Christ.)   If I hadn't called Jenna..then I would have been struggling on my own to learn what to do, instead of drawing from the experiences of 700 others....if I hadn't thought she had a form of dwarfism ...then we wouldn't have ended up in Delaware...where we were referred to a geneticist who is actually known as a OI expert...if her reflux hadn't been so bad...we would have been much rougher with her....if she hadn't had untreated jaundice...she wouldn't have ended up in the hospital getting x-rays.  You see where I'm going here?   God appointments.

    Lucy not only has this disease but has a very rare type - type V.

Most of the information I'm am posting below came from the OI foundation's website...www.OIF.org.

From xray

General Info

• The number of Americans affected with OI is thought to be 25,000-50,000. 
• The range is so wide because mild OI often goes undiagnosed.
• In addition to fractures people with OI often have muscle weakness, hearing loss, fatigue, joint laxity, curved bones, scoliosis, blue sclerae, dentinogenesis imperfecta (brittle teeth), and short stature. Restrictive pulmonary disease occurs in more severely affected people.  These things are not known to affect type V.
• OI is caused by an error called a mutation on a gene that affects the body’s production of the collagen found in bones, and other tissues. It is not caused by too little calcium or poor nutrition.  Type V's do not have collagen deficiency, they have an unusual bone matrix.  The bone looks like "mesh" under the microscope.
• OI is variable with 8 different types described in medical literature.  Up until 10-15 years ago, any mutation of OI that could not be defined in the first 3 types, was given a type IV diagnosis.  Only in the last decade have researchers found enough patients with similar characteristics, that they could define additional types.
• The types range in severity from a lethal form to a milder form with few visible symptoms.
• The specific medical problems a person will encounter will depend on the degree of severity
• A person with mild OI may experience a few fractures while those with the severe forms may have hundreds in a lifetime.

Types of OI

The appearance of a child or adult with OI and the problems he or she might have are influenced by the type of OI.

Type I:

• OI Type I is the mildest and most common form of the disorder. It accounts for 50 percent of the total OI population.
• Type I is characterized with mild bone fragility, relatively few fractures, and minimal limb deformities. The child might not fracture until he or she is learning to walk.
• Shoulders and elbow dislocations may occur more frequently than in healthy children.
• Some children have few obvious signs of OI or fractures. Others experience multiple fractures of the long bones, compression fractures of the vertebrae, and chronic pain.
• The intervals between fractures may vary considerably.
• After growth is completed, the incidence of fractures decreases considerably.
• Blue sclerae are often present.
• Typically, a child’s stature may be average or slightly shorter-than-average as compared with unaffected family members, but is still within the normal range for the age.
• There is a high incidence of hearing loss. Onset occurs primarily in young adulthood, but it may occur in early childhood. 
• Dentinogenesis imperfecta is often absent.
• OI Type I is dominantly inherited. It can be inherited from an affected parent, or, in previously unaffected families, it results from a spontaneous mutation. Spontaneous mutations are common. 
• Biochemical tests on cultured skin fibroblasts show a lower-than-normal amount of type I collagen. Collagen structure is normal.
• People with OI Type I experience the psychological burden of appearing normal and healthy to the casual observer despite needing to accommodate their bone fragility.
• The absence of obvious symptoms in some children may contribute to problems at school or with peers.
• Significant care issues that arise with OI Type I include gross motor developmental delays, joint and ligament weakness and instability, muscle weakness, the need to prevent fracture cycles, and the necessity of spine protection. 
• Family members should carry documentation of the OI diagnosis to avoid accusations of child abuse at emergency rooms.
• Treatment with bisphosphonates is not routinely recommended. 
• The treatment plan should maximize mobility and function, increase peak bone mass, and develop muscle strength. Physical therapy, early intervention programs, and as much exercise and physical activity as possible will improve outcomes.

Type II:

• OI Type II is the most severe form. 
• At birth, infants with OI Type II have very short limbs, small chests, and soft skulls. Their legs are often in a frog-leg position.
• The radiologic features are characteristic and include absent or limited calvarial mineralization; flat vertebral bodies; very short, telescoped, broad femurs; beaded and often broad short ribs; and evidence of malformation of the long bones. 
• Intrauterine fractures will be evident in the skull, long bones, or vertebrae.
• The sclerae are usually very dark blue or gray.
• The lungs are underdeveloped.
• Infants with OI Type II have low birth weights.
• Respiratory and swallowing problems are common. 
• Macrocephaly may be present. Microcephaly is rarely present.
• Infants with OI Type II usually die within weeks of delivery. A few may survive longer. Cause of death is usually respiratory and cardiac complications.
• OI Type II results from a new dominant mutation in a type 1 collagen gene or parental mosaicism. Similar extremely severe types of OI, Types VII and VIII, can be caused by recessive mutations to other genes.
• Genetic counseling is recommended for parents of a child with OI Type II before any future pregnancies. 
• Significant care issues that arise with OI Type II include obtaining an accurate diagnosis, getting genetic counseling, the family’s need for emotional support, and management of respiratory and cardiac impairments. Infants with OI Type II who can breathe without a respirator and those with severe OI Type III may be candidates for off-label treatment with bisphosphonates. At this time, pamidronate (©Aredia) is the only bisphosphonate that has been studied in infants who have OI. Treatment research is ongoing.

Type III:

• OI Type III is the most severe type among children who survive the neonatal period. The degree of bone fragility and the fracture rate vary widely.
• This type is characterized by structurally defective type I collagen. This poor quality type I collagen is present in reduced amounts in the bone matrix.
• At birth, infants generally have mildly shortened and bowed limbs, small chests, and a soft calvarium.
• Respiratory and swallowing problems are common in newborns. 
• There may be multiple long-bone fractures at birth, including many rib fractures.
• Frequent fractures of the long bones, the tension of muscle on soft bone, and the disruption of the growth plates lead to bowing and progressive malformation. Children have a markedly short stature, and adults are usually shorter than 3 feet, 6 inches, or 102 centimeters.
• Spine curvatures, compression fractures of the vertebrae, scoliosis, and chest deformities occur frequently.
• The altered structure of the growth plates gives a popcorn-like appearance to the metaphyses and epiphyses.
• The head is often large relative to body size.
• A triangular facial shape, due to over development of the head and under development of the face bones, is characteristic.
• The sclerae may be white or tinted blue, purple, or gray.
• Dentinogenesis imperfecta is common but not universal.
• The majority of OI Type III cases result from dominant mutations in type I collagen genes. Often these mutations are spontaneous. Similar extremely severe types of OI, Types VII and VIII, are caused by recessive mutations to other genes.
• Genetic counseling is recommended for asymptomatic parents of a child with OI Type III before any future pregnancies.
• Significant care issues that arise with OI Type III include the need to prevent fracture cycles; the appropriate timing of rodding surgery; scoliosis monitoring; respiratory function monitoring; the need to develop strategies to cope with short stature and fatigue; the family’s need for emotional support, especially during infancy; and the off-label use of bisphosphonates.
• It is also important to address difficulties with social integration, participation in leisure activities, and maintaining stamina. 
• The treatment plan should maximize mobility and function, increase peak bone mass and muscle strength, and employ as much exercise and physical activity as possible.

Type IV:

• People with OI Type IV are moderately affected. Type IV can range in severity from relatively few fractures, as in OI Type I, to a more severe form resembling OI Type III.
• The diagnosis can be made at birth but often occurs later. 
• The child might not fracture until he or she is walking.
• People with OI Type IV have moderate-to-severe growth retardation, which is one factor that distinguishes them clinically from people with Type I.
• Bowing of the long bones is common, but to a lesser extent than in Type III. 
• The sclerae are often light blue in infancy, but the color intensity varies. The sclerae may lighten to white later in childhood or early adulthood.
• The child’s height may be less-than-average for his or her age.
• It is common for the humerus and femur to be short
• Long bone fractures, vertebral compression, scoliosis, and ligament laxity may also be present.
• Dentinogenesis imperfecta may be present or absent.
• OI Type IV has an autosomal dominant pattern of inheritance. Many cases are the result of a new mutation.
• This type is characterized by structurally defective type I collagen. This poor quality type I collagen is present in reduced amounts in the bone matrix.
• Significant care issues that arise with OI Type IV include the need to prevent fracture cycles; the appropriate timing of rodding surgery; scoliosis monitoring; the need to develop strategies for coping with short stature and fatigue; the family’s need for emotional support, especially during infancy; and the off-label use of bisphosphonates.
• Family members should carry documentation of the OI diagnosis to avoid accusations of child abuse at emergency rooms.
• It is also important to address difficulties with social integration, participation in leisure activities, and maintaining stamina.
• The treatment plan should maximize mobility and function, increase peak bone mass and muscle strength, and employ as much exercise and physical activity as possible.

***Microscopic studies of OI bone identified a subset of people who are clinically within the OI Type IV group but have distinctive patterns to their bone. Review of the clinical histories of these people uncovered other common features. As a result of this research, two types Type V and Type VI were added to the Sillence Classification. Regarding these types, it is important to note the following:

They do not involve deficits of type 1 collagen.

Treatment issues are similar to OI Type IV.

Diagnosis requires specific radiographic and bone studies.

Type V:

• OI Type V is moderate in severity. It is similar to OI Type IV in terms of frequency of fractures and the degree of skeletal deformity.
• The most conspicuous feature of this type is large, hypertrophic calluses in the largest bones at fracture or surgical procedure sites.
• Hypertrophic calluses can also arise spontaneously.
• Calcification of the interosseous membrane between the radius and ulna restricts forearm rotation and may cause dislocation of the radial head.
• Women with OI Type V anticipating pregnancy should be screened for hypertrophic callus in the iliac bone. 
• OI Type V is dominantly inherited and represents 5 percent of moderate-to-severe OI cases.

 ( another radiologic finding that is not discussed in the OIF's description is that there is a dense, bright band, seen at the growth plates on x-ray.  This is one of the main reasons Lucy was given this diagnosis.  She hasn't any large callus's yet, and she is not old enough to have had her radius and ulna fuse together.)

Lucy was diagnosed based on the following:

 - dense, bright band, seen at the growth plates of her metaphysis

 - low bone density, number of fractures

 - and she DOESN'T have a collagen deficiency

   Ergo....type V...until proven otherwise.

Type VI:

• OI Type VI is extremely rare. It is moderate in severity and similar in appearance and symptoms to OI Type IV. 
• This type is distinguished by a characteristic mineralization defect seen in biopsied bone. 
• The mode of inheritance is probably recessive, but it has not yet been identified.
• Recessively Inherited Types of OI (Types VII and VIII):
• Two recessive types of OI, Types VII and VIII, were identified in 2006. Unlike the dominantly inherited types, the recessive types of OI do not involve mutations in the type 1 collagen genes.
• These recessive types of OI result from mutations in two genes that affect collagen
• the cartilage-associated protein gene (CRTAP)
• the prolyl 3-hydroxylase 1 gene (LEPRE1)
• Recessively inherited OI has been discovered in people with lethal, severe and moderate OI. There is no evidence of a recessive form of mild OI. Recessive inheritance probably accounts for fewer than 10 percent of OI cases.
• Parents of a child who has a recessive type of OI have a 25 percent chance per pregnancy of having another child with OI. Unaffected siblings of a person with a recessive type have a 2 in 3 chance of being a carrier of the recessive gene.

Type VII:

• Some cases of OI Type VII resemble OI Type IV in many aspects of appearance and symptoms.
• Other cases resemble OI Type II, except that infants have white sclerae, small heads and round faces.
• It is common for leg bones, humerus and femur to be short. 
• Short stature is common.
• Coxa vara is common.
• OI Type VII results from recessive inheritance of a mutation in the CRTAP gene. Partial (10%) expression of CRTAP leads to moderate bone dysplasia. Total absence of the cartilage-associated protein has been lethal in all identified cases.

Type VIII:

• Cases of OI Type VIII are similar to OI Types II or III in appearance and symptoms except for white sclerae.
• OI Type VIII is characterized by severe growth deficiency and extreme under-mineralization of the skeleton.
• It is caused by absence or severe deficiency of prolyl 3-hydroxylase activity due to mutations in the LEPRE1 gene.

Lucy Q & A

There are a couple of questions people ask me all the time:

Q.  Will she grow out of it?
A.  OI is a genetic disorder that is present throughout a person’s lifetime. The frequency of fractures may decrease after puberty, when growth stops. Later, it may increase again in women with the onset of menopause and in men due to age-related changes in their endocrine system.


Q.  What are the chances of having another baby like Lucy?
A.  About the same chance you have of having a child with OI.  We have no family history of the disease.  Therefore, it is likely that she is a new mutation.  We have only a 1% or 2% chance of having a another child with OI.


Q.  Could Ella have a child with OI
A.  No, her chances are the same as the general population.


Q.  Can Lucy have children and will they have OI?
A.  OI does not affect fertility. Many men and women who have OI have children. Some women who have OI may experience pregnancy complications due to skeletal problems. It is important that all young people with OI receive information about their condition and reproductive health.  She has a 50% chance of having a child with OI. If she had a child that had OI, they would have the same type but the severity could vary.


Q. What severity is Lucy?
A.  Clinically, according to our geneticist, she is mild because she doesn't have any deformity, ie.  bowing of her bones or disproportion such as short limbs or large head.  However, she has had a good many breaks, including compression fractures of her spine, which indicates a more moderate to severe condition.  She has only a slight amount of bowing in one of her arms and her fibulas are longer than her tibias.  There are only small indicators of mild deformity. 


Q.  I have said that the Dr.s have told us that they have never seen anything like Lucy.  Why do they say that?
A.  Well, first off, only a handful of Doctors in the world have even seen a type V, and even less are knowledgeable enough to treat them.  However, Lucy has even confounded the experts.  She has metaphyseal flaring in her bones.  That means the ends of her bones flare out like bow-ties.  This not only confounds our physicians,  but even the world's foremost expert on OI, Dr. Glorieux, from Montreal, Canada, just looked at me when asked about this and said, "Let's just say she has type V for now." Because he hasn't seen other patients with her bone structure.  Also, her neck, there is not a published case of a patient with OI with a neck like Lucy's. "The structure isn't right".  We don't know what that means and we are just waiting to see how she does as she grows. More than likely her neck was broken during birth. She truly is a unique little snowflake.  There is no way to predict what her future holds.

From xray

Q. How many fractures has Lucy had?
A.  13, 7 at birth with included 5 broken ribs, shoulder blade, and neck.  Since then: forearm, 3 femur (upper leg), and 2 compression fractions of the vertebral bodies in her spine.  So, far she only "cracks", which means they are not displaced.  She has an extraordinarily high pain tolerance, two of the femur fractures we never even knew about, we just saw signs of healing on x-ray.

From xray

Evidence of Crushed vertebral body (this is Lucy's x-ray):

From xray

Q.  Will Lucy need any surgeries?
A.  We are anticipating several surgeries.
      - She may need to have her long bones rodded to provide internal splinting and protect her from severe displacement in the event of a fracture.  We will not have any surgeries done on her forearms since we are anticipating those bones to fuse together because of her type.
     - Her fibula is longer than her tibia in her lower leg.  They may want to shorten her fibula's as concern grows regarding interference with walking.


Example of rodded legs:

From xray

*disclaimer - This image is not of anyone that I know, I found this image in a google search.


Q.  When will these surgeries happen?
A.  There is a delicate balance between waiting as long as possible so that the largest size rods can be used and timing the surgery before a severely displaced fracture.  In general fracture rate is monitored along with her mobility.  The general rule is, once she starts pulling to stand, we need to start thinking about rodding.


Q.  Does this disease affect her mentally?
A.  Actually, There are studies being done to investigate if people with OI are more intelligent than the average population.  We do not see any signs of a cognitive challenge in Lucy.  Also, there is no study on this but also generally speaking, children with OI are generally happier than their peers.  My theory is that they have a "Don't sweat the small stuff" type attitude.


Q.  Is there a treatment?
A.  Yes, but first you must qualify for the treatment.  The guidelines are 3 long bone fractures in a year or one compression fracture.  The drug she receives is called Pamidronate.  She gets it by IV infusion over 3 days every 2 months.  There are other protocols that are used that are for shorter durations, frequency, and dosages, but we have chosen to act aggressively in light of the number of vertebral fractures she has already had before she was even 7 months old.  We have chosen the dosage for moderate to severe OI patients.  There is another drug that we may change to when Lucy turns 2 called ZOLE or zoledronic acid - also known as Reclast.  She would take it less often in a lesser amount.  It is supposed to work better with fewer side effects.  The studies that are going on right now with Zole are very exciting!


Q.  How long will she take the treatment?
A.  She will take the treatment until she stops growing...sometime in her teens. However, as her growing slows with age, there will be longer periods of time between treatments.


Q. What are the drawbacks of the treatment?
A.    Potential drawbacks:  
      - Her bone density must be closely monitored.  We have bone density scans or DXA scans twice a year. If her bones were to become hyper-dense.  They could shatter or have severe fractures that will not heal.
      - When taking this drug, OI patients tend to feel so much better that they can be a danger to themselves.
      - Once you begin taking the drug, it is not wise to stop taking it because as the bone grows and new untreated bone develops, the fracture risk increase at the junction of treated  and untreated bone.  It requires a commitment.

Rodded Bone that also shows treatment lines: (image found on google)

From xray

      - As bone density increases, the risk of displaced fractures increases.  A severely displaced fracture could have life altering affects.   Even treated OI bone is still OI bone. It is lacking some basic element that typical bones have...such as collagen or, in Lucy's case, an organized bone matrix.  This sounds like a no-brainer right?  Why would you give your child this drug?  Because it lowers the frequency of fractures and lowers bone pain.  It allows children with OI to have a childhood.  Some children can go years between fractures...whereas before they were fracturing monthly.  Also, having internal splinting such as rods helps to prevent displacement. 


Q.  You talk about therapy a lot.  What can therapy do for her?
A.  We can strengthen her muscles as much as possible.  The stronger her muscles are the more they protect her fragile bones.  Even when our children have fractures, treatment never stops and therapy never stops.  Every activity she does MUST be looked at as an opportunity for therapy.  The water is our greatest resource...I have Lucy in the pool as much as possible.  Its provides a hands off approach to PT and provides natural resistance.  It is the safest environment she can be in.  When she is in the water she can put weight on her legs.  She can play uninhibited in the water.


Q.  Will Lucy be in a wheelchair?
A.  There will be times in her life when Lucy will need a wheelchair.  Possibly during a fracture, or potentially for her own protection in crowds, or possibly when traveling long distances to avoid damage to her joints.  It is very possible that she will not need a wheelchair most of the time and certainly not at home.  I used to have a lot of anguish at the thought of her being in a wheelchair, now I see it as a tool for freedom.



    If you see me and you would like to ask me a question about Lucy, I most certainly do not mind.  There is not a lot of awareness out there about her disease and I would love to educate you.  That way, you are no longer afraid of my daughter, but you can come along side us, in encouraging her and promoting her confidence.  You can help to protect her if you see us out.  As she grows you can include her in birthday parties and invite her for sleep overs.   You will not feel sorry for her but will see her as a regular child who wants to participate with the other kids.

Here's one famous person that you may know that has OI:

Atticus Shaffer from ABC's Comedy "The Middle"

From xray