I haven’t thought or written much about human genetics since COVID hit, instead cranking out articles about the novel coronavirus and the…
Today, May 6th, is Wishbone Day, to raise awareness about osteogenesis imperfecta (OI).
Also known as “brittle bone disease,” OI is a consequence of mutations that disrupt the highly organized structure of collagen, a major component of connective tissues. Collagen accounts for more than half the protein in bone and cartilage, and is also part of skin, ligaments, tendons, and the dentin of teeth.
Because OI is due to a deficit of collagen, eating more calcium doesn’t help – the advice given to members of a family I wrote about here. Before many genes behind OI were identified, some parents of children with OI were suspected of child abuse, especially when a second child had fractures too.
A Collection of Collagen Conditions
In my human genetics textbook, I describe OI as the “disorders of orderly collagen.” The complexity of the genetics behind OI is why 18 forms are recognized.
More than 35 collagen genes encode more than 20 types of collagen molecules. Mutations in these genes lead to a variety of medical conditions – besides OI, they lie behind Alport syndrome, chondrodysplasia, osteoarthritis, Ehlers-Danlos syndrome, and Stickler syndrome.
Collagen disorders have bodywide effects because the protein is ubiquitous and the precise structure easily disrupted, even by slight alterations that might have little effect in proteins with less regular shapes. Trimmed from a precursor protein, collagen consists of many repeats of a trio of simple amino acids, forming three long chains. Interactions of the twisted chains with water and the electrical charges on some of the amino acids coil the chains into a tight triple helix. After enzymes snip off the raggedy ends, the collagen threads knit into fibrils and networks, which ultimately hold the body together.
This morning I was just about to post yet another COVID article, when a good friend forwarded an email from a colleague, a French teacher at a high school in Maryland. Christina Crise’s son Andrew is 11 months old, and she gave permission to share his story.
“Andrew has osteogenesis imperfecta type 11, also known as Bruck syndrome, one of the rarest forms. It is when the patient has the brittle bones of osteogenesis imperfecta and the congenital joint contractures of arthrogryposis multiplex congenita (AMC). In AMC, the patient is born with joints that are locked or frozen and lack a full range of motion. Bruck syndrome is a recessive form of OI in which both parents must be carriers of the affected gene. There is a 25% chance per pregnancy of the child developing the condition.
At birth, Andrew was diagnosed with arthrogryposis. We knew that arthrogryposis often had a separate underlying cause, but we did not know yet what had caused Andrew’s to manifest.
When Andrews was four weeks old, we took him to the ER because his arm was unnaturally swollen and hot to the touch. The ER discovered a fracture that we could not explain. Further x-rays revealed several additional fractures, all in various stages of healing. Andrew was transferred to Johns Hopkins, where he remained for three days as they ran a battery of tests. Very quickly, the doctors zeroed in on OI type 11, or Bruck syndrome, as the probable real diagnosis. However, we needed genetic tests to confirm it.
In September 2020, six weeks after his stay at Hopkins, we got his genetic results back. Andrew became the 17th known case of Bruck syndrome and the 3rd known case of Bruck syndrome type 2 currently in the world. Type 2 is more severe and is caused by a mutation in the PLOD2 gene, whereas Bruck syndrome type 1 is a mutation of the FKBP10 gene. Neither type affects sight, hearing, or intelligence. A person with either type of Bruck syndrome has a regular life expectancy.
We are blessed to be close to some amazing specialists in the Johns Hopkins and Kennedy-Krieger system who have treated or are currently treating other patients with Bruck syndrome. Andrew’s treatment may have gone in a completely different direction than we originally thought, but our son is going to do amazing things!
Facts About OI
Here are some facts that Christina Crise assembled from the Osteogenesis Imperfecta Foundation (OIF) and the National Organization for Rare Disorders (NORD) websites:
• An estimated 25,000 to 50,000 people are living with OI in the United States.
• OI has no cure, but treatments can reduce the frequency of fractures.
• Any part of the body that contains collagen is impacted by this diagnosis, including hair, skin, and the lungs.
• The OIF recognizes 18 types of OI, identified by the genes that are mutated and how the collagen deficiency impacts the body. Types 1 through 4 are more common; the others are considered rare. More types are being identified as more mutations are discovered.
• Each type of OI can be further classified as mild, moderate, and severe. Frequency of fractures and how much the collagen deficiency affects the rest of the body determine severity. People with OI often refer to themselves by their type first followed by their level of severity, for example, type 1 moderate, type 3 mild, or type 5 severe.
Misconception #1: A person with OI can be cured just by taking additional supplements, eating a healthy diet full of natural vitamins, and drinking lots of milk.
Reality: While many people with OI take calcium, vitamin D, and collagen supplements, that’s no cure. There is no cure for OI. It is a genetic disorder in which the collagen deficiency is written into the DNA. Supplements and a healthy diet can (sometimes) help but they do not cure.
Misconception #2: A person with OI has cognitive and learning delays as well as the physical challenges.
Reality: Not so! OI is a physical condition. If a person with OI also has cognitive and learning delays, there is a separate diagnosis causing it. Most people with OI have normal to above normal intelligence.
Misconception #3: A person with OI will fracture every time there is a small trauma to their bones.
Reality: Yes, they could. There is no set rule that every trauma or certain types of trauma will always cause a fracture. Most COULD cause one, which is why you should be careful and always assess a child/person with OI after a trauma to look for a fracture. Some people with OI fracture constantly, while others will go for long periods of time without a single fracture. Sometimes, multiple fractures will happen on separate occasions within a short time period. This is known as a fracture cluster.
Misconception #4: I’m scared to handle your baby/child with OI. I’m scared that *I’ll* cause a fracture!
Reality: I get this one. I really do. However, babies with OI are still babies. Children with OI are still children. They need love, affection, and play just like every other baby and child. One thing that has really helped me overcome my fear is to change my language around fractures. As long as I was not doing something inherently dangerous, I did not cause the fracture. Andy’s OI caused the fracture.
Misconception #5: A person with OI can never live a normal life.
Reality: Absolutely, not at all true. With the right adaptive aids and treatment options, a person with OI can live a long, full, and (dare I say it) “normal” life. It may look different from how you or I live our lives but that does not make it “abnormal,” which is the natural opposite of “normal.” People with OI go to regular schools, play sports, get involved in the band or plays, go to college, start a career, live independently, get married and have kids, and live a very similar life to yours.
Thank you Christina!