I am a genetic carrier of Duchenne. My mother was not. This means I was one of the 1:4600 females born with this genetic mutation. As a child, I had muscle cramps, ‘growing pains’ my parents would say. And from those ‘growing pains,’ 20 years later, my sons were diagnosed and I first learned that I was a carrier.
All mothers in our community have a story, the journey that led us to Duchenne. It’s not a journey we would have chosen, but it’s our journey nonetheless. When PPMD talks about our commitment to ‘every single one’ in this community, that commitment includes carriers.
In our over 20 year history, PPMD has identified gaps in the Duchenne landscape and tried to expand our knowledge of various aspects of this complicated disease. That’s why I am particularly proud to formally announce PPMD’s carrier initiative.
What are carrier issues?
There is widespread consensus that female carriers of Duchenne or Becker are at risk for symptoms of muscular dystrophy. But what are those risks? We talk about a spectrum of skeletal muscle manifestations and a cardiac risk. Are there more? Is there additional stress? Do we have cognitive and behavior concerns similar to our sons? Emotional stress?
Having spoken with any number of women in our community, it is clear that there is a spectrum of ways to ‘manifest’ or have symptoms related to the genetic mutation. The risks fall primarily into four clinical categories: cardiac, skeletal, cognitive (processing and behavior) and stress. We have all heard the term X-linked inactivation, where the X-chromosome that includes the healthy dystrophin gene simply turns off. This leaves the X-chromosome with the altered dystrophin gene active leading to symptoms of Duchenne or Becker in some carrier women.
And we must remember that some girls HAVE Duchenne. These women need to be followed rigorously, included in trials and assured access to therapies.
What is a manifesting carrier?
I think all carriers are manifesting. I said that out loud to some of the clinicians and watched as they shook their heads in disagreement. It did not dissuade me from the idea. As carriers, we are at risk for heart disease. As carriers we are at risk for skeletal muscle weakness. As carriers we are at risk for cognitive and behavior issues. And as carriers, in the backpack of our lives, we know that we carry a mutation in the dystrophin gene on one of our X-chromosomes and this, at times, gives all of us pause. I believe there absolutely is an emotional aspect associated with being a carrier of Duchenne or Becker.
Like everything we do, PPMD will look at carrier issues from a variety of angles, through a variety of lenses.
Last year, we announced that PTC Therapeutics had awarded PPMD with a STRIVE Grant. As one of a select group of organizations to receive this award, PPMD pledged to raise awareness about carrier issues. We will focus both on women who are carriers or at risk to be a carrier and on health care professionals serving this community.
This project will provide women who have given birth to children diagnosed with Duchenne and their female relatives:
In addition, we are excited to announce a clinical study, already underway. The Female Side of Duchenne includes moms and female relatives of people with Duchenne. PPMD has teamed with leaders in the Duchenne community to study 300 women.
The study will:
We will also continue to provide genetic counseling support for women who are carriers or at-risk to be carriers, and explore methods to improve access to carrier testing. This includes identifying ways to subsidize the cost of carrier testing. The last thing anyone in our community needs is the burden of another expense in an already exorbitantly costly disease.
In addition, we will publish a systematic literature review about Duchenne carriers. This comprehensive review will allow us to better understand existing carrier research, guidelines already in place for carrier care, and provide a summary of knowledge (what do we know about prevalence, symptoms, diagnostic approaches?). This will be the foundation that we can use to continue building our knowledge about carrier issues.
Taking care of ourselves – our mothers, sisters, daughters, cousins – is essential. To understand our natural history as carriers is important to maintaining the momentum in Duchenne research and optimizing care.
We are excited about this new initiative – stay tuned for ways you can be part of this important endeavor.
And happy Mother’s Day to all the incredible moms in our community!