worldduchenne Duchenne: Breaking Barriers, News

Breaking Barriers: The story of Anil Jalhan

Meet Anil Jalhan, also known as “The DMD Guy” on social media. At 26 years old, he shares his journey with Duchenne muscular dystrophy (DMD). Despite facing physical challenges, Anil broke barriers by graduating from university and become an independent individual. As a Duchenne Ambassador, he aims to create a positive community, raise awareness, and inspire others to share their stories.

About Anil Jalhan

“My name is Anil and I am 26 years old, living in the UK. I thought I would talk about my Duchenne Muscular Dystrophy (DMD) journey. Prior to my diagnosis I grew up not knowing I had it and even my parents didn’t know. As I was the first boy born after my parents had two healthy children, it was likely I would be healthy too. Eventually we found out that boys were mostly affected and how it can be passed down in the family.

I don’t remember much, but I remember walking to nursery and school with my mother. Eventually my mother would receive a phone call from the school informing her that I kept falling frequently and was moving much slower than other kids. This was the very first signs of the condition. Once we decided to get me checked out, it was clear what was wrong with me. I was diagnosed with Duchenne Muscular Dystrophy (DMD)

After the confirmed diagnosis, my future was full of questions and uncertainty, as I didn’t know how it would affect me. I would continue to move forward while going through these physical changes. I would experience being wheelchair bound and weak whilst enjoying my primary school days.

Once the time was right, I would later make my transition to my new special needs school. This was a huge moment of my life, as the school helped me become who I am today. Giving me the confidence to become an independent disabled person.

I am the person today because of this experience. I believe my disability has taught me many valuable life lessons and has helped shape the person I am today. My journey has been difficult with many barriers and many still to come. But I aim to just keep going. I usually like to say my future may not be clear, I may have a disability, but this will not stop me from achieving my dreams.”

Daily life with Duchenne

“I want to say being physically weak and all the constant changes I have and will go through. But I did come to the realization that it’s something I had to just accept and I could still pursue my dreams. One of my dreams was to graduate from University and I did back in 2019. With the help of assistive technology this was possible. One major barrier was my housing situation which I will talk about in another post hopefully. But this really was a serious one which stopped me from getting out of the house and sometimes even going to university.”

Duchenne Ambassador

“With Duchenne and my page, my goal has always been to create a positive Duchenne community for other DMD guys like myself. Also to raise as much awareness as possible. The WDAD has a similar goal which really motivated me to get more involved. I also wanted to share my story to hopefully encourage others to share theirs.”

Interpreting ‘Breaking Barriers’

“As someone living with Duchenne Muscular Dystrophy (DMD) like many we go through many life changing moments during our Duchenne journey. With many battles and emotional moments. From not being able to walk or losing the ability to play your favorite sport. I think my interpretation of ‘breaking barriers’ is to have the ability to accept these changes and adapt to them while trying to remain positive. Lastly, I also think going through all these trials and tribulations and still being able to achieve something is breaking barriers. No matter how big or small the goal is.”

Key message

“The journey can be quite emotional at times and tough. The only thing we can do is try our best to enjoy life no matter how long it is. Also to create these precious memories. Through my stories I hope to show the reality of Duchenne but also try and show how life could be enjoyed as well. Another general message to the world is that everyone is affected by this, men, women and kids so let’s do something about it.”

Future goals

“I hope to see more people with Duchenne continue to break barriers and to share their story. Further increasing the awareness for Duchenne and Becker Muscular Dystrophy. In terms of my future I also will continue to overcome challenges. I hope to make use of any opportunities I get to raise awareness for Duchenne. Lastly I remain hopeful that there will be a cure in the future mainly because of our awareness efforts.”

We invite you to follow Anil’s story via Instagram and TikTok. Here he shares messages on resilience and the pursuit of joy in life. All while advocating for a future cure through increased awareness efforts. We are looking forward hearing your story about breaking barriers!

Instagram & TikTok: thedmdguy

Brad Miller
worldduchenne Duchenne: Breaking Barriers, News

Breaking Barriers: The Story of Brad Miller

In this interview, we meet Brad Miller (47), a Canadian blogger living with Becker muscular dystrophy (BMD). Brad shares his remarkable journey of adapting to challenges posed by the rare disease, and pursuing his passions with confidence and determination. He talks about his childhood experiences to creating his blog, “My Beckers Story,” and founding “Laps for Muscular Dystrophy.” Brad’s story is an inspiring testament to breaking barriers and raising awareness for BMD.

About Brad Miller

“My name is Brad and I’m a Canadian blogger living in Ontario with Becker muscular dystrophy. As a child I was having trouble keeping up with the other kids my age. This led to a visit to a family doctor who thankfully had some knowledge about muscular dystrophy. At the time, my enlarged calf muscles grabbed his attention. So, at the age of 10 I was sent off for some testing which also included me having a muscle biopsy. After that my parents were given the news that I have Becker muscular dystrophy.”

Becker muscular dystrophy and daily life

“As a child with Becker muscular dystrophy, I could still enjoy riding my bike and playing with friends, but certain activities like jumping, climbing trees, or participating in running sports were challenging for me. However, I didn’t let these limitations bother me and learned to adapt at a young age, thoroughly enjoying my childhood. The real challenges surfaced in my late teens, experiencing frequent falls and needing several days to recover after pushing myself too far physically, especially during trips to amusement parks. Nowadays, I do my best to adapt to the challenges that come my way, as walking becomes more difficult. I’ve started using a mobility scooter for longer distances and a cane when required. Adapting to my changing needs is an ongoing part of my life with Becker muscular dystrophy.

Following dreams with Becker MD

Having this condition never stopped me from following my dreams. Throughout my life, I’ve pursued my passions, including writing and performing my songs. I’m proud to have published two articles online, featuring my list of the Top 10 vehicles for people with disabilities and reviewing a newly accessible vehicle. Unfortunately, a few years ago, I suffered a work-related injury, leading me to stop working. However, this didn’t deter me; instead, it inspired me to create the My Beckers Story blog, where I share my experiences of living with Becker muscular dystrophy. A few years later, I founded Laps for muscular dystrophy, where racing teams contribute to raising awareness and funds for muscular dystrophy charities. My journey has been about adapting and persisting, pursuing my passions and advocating for others in similar situations.”

My goal for WDAD

“For WDAD in 2023, it is my passion for raising awareness and understanding of the issues we face. As I really believe when people better understand our daily lives it can result in more support of our community. With the end result being more support of muscular dystrophy charities and of the important research & studies currently taking place. After all, the hope of many is seeing new treatments and the possibility of one day finding a cure.”

About the Breaking Barriers Theme

“To me, this year’s WDAD theme represents the determination of our community to support each other by working together to advance the cause of raising much-needed awareness and funds to help improve the lives of current and future generations. I think raising awareness is a great way of breaking barriers by making more people aware of the unique challenges we face. This resulting in more support and understanding.”

Why I’m joining as Becker Ambassador

The main reason I have decided to share my story is to show others they are not alone. To also show people that perseverance in life is so important. I’ve certainly faced many challenges in life. Some related to living with Becker Muscular Dystrophy others just the regular challenges of life. In my case I survived being bullied as a child as unfortunately the other children would make fun of the way I walk, call me names and once even spit on me. It was easy but I survived and still no child living with any form of Muscular Dystrophy should have to deal with being bullied. So, another hope of mine in raising awareness of BMD is that it makes more children aware of those living with MD so that future generations don’t have to deal with bullying. Another hope of mine is that reading my story helps parents better understand what it is like to live with BMD to hopefully show people we can live our lives to the fullest, have careers, start families and enjoy life.

Since the start of sharing my story, I’ve shared it openly and honestly by not shying away from addressing any issue affecting those with disabilities. Simply because I believe we can learn a lot from each other’s stories. That is why I often encourage others to start sharing their stories as it certainly can make a huge difference in people’s lives knowing they are not alone in their experiences. In a way letting them know we are all in this together with the same hope of one day seeing a cure for Muscular Dystrophy.”

Key Message

“So, let’s keep sharing our stories and raising awareness. Supporting WDAD is key in encouraging everyone. Even those outside our community to join us in the fight against Muscular Dystrophy.”

We are inviting you to follow Brad with his Becker story through his website and social media channels:

Bert-Gooris
worldduchenne Duchenne: Breaking Barriers, News

Breaking Barriers: The Story of Bert Gooris

Meet Bert Gooris, a 32-year-old from Belgium, living with Duchenne muscular dystrophy. This year, for World Duchenne Awareness Day (WDAD), he is one of our Duchenne Ambassadors. Over the next few weeks, Bert will be sharing his journey on breaking barriers in his personal life.

About Bert Gooris

“Hello, I’m Bert Gooris, a 32-year-old living with Duchenne muscular dystrophy in Leuven. Though I reside with my parents, I have my own space in the house, complete with a desk, room, and bathroom. I am a positive person and a dedicated family man. My 21-year-old sister also lives with us, and my older brother, who doesn’t have Duchenne, resides in Landen. It was a shock for me and my family to learn that my sister is a carrier of Duchenne muscular dystrophy, when she was 18 years old. Recently, I got a tattoo symbolizing the strong bond between me and my siblings. My parents have always supported my participation in various activities, like playing soccer and riding my bike. Although I faced bullying in school, I stood up for myself and continued my education smoothly, making some of the best memories during my college years.”

Daily Life with Duchenne

“Due to Duchenne, I had to readjust my ideas about what I wanted to become in the future. At home, when we talked about further studies, I wanted to attend culinary school to become a chef. However, it soon became clear that this would not be feasible in the long run due to the loss of function in my arm and leg. That’s why I decided to pursue something administrative because working with computers would remain possible for a longer time. Even in football, I had to admit that playing matches became too difficult, and eventually, I couldn’t participate in training sessions anymore, so I wouldn’t become a footballer.”

Duchenne Ambassador

“At school, I had to stand up for myself, explain that I had the disease, explain why I couldn’t run as fast, and why I was heavier than others. This made me a person who cannot tolerate injustice and will stand up for the weaker ones in society. As I grew older, I encountered more stories of injustice or shortcomings, and I became more aware that many people still don’t know about the disease despite the efforts made. That’s why I see it as my duty, as an adult living with Duchenne, to take on the role of ambassador now. I want to share my story with other individuals with Duchenne to encourage and support them. By doing so, I aim to create global awareness.”

Interpreting ‘Breaking Barriers’

“Well, it’s about time we dare to break those barriers and push for change. Change in inclusion, belonging, being informed about medication, assistive devices, the right to certain benefits, and the steps to follow during important milestones in life. It should be clear for everyone what rights they have and where to access relevant information. The time has come for people with disabilities to be fully accepted by society, and administrative processes for them should be significantly streamlined.”

Key Message

“It’s still a tough world for people with disabilities. We are just like any other individuals with the right to be fully included, 100%. We lead lives just like everyone else. If we collaborate and are truly heard, we can overcome many obstacles together.”

Future Plans

“In the future, everyone should be aware of these diseases. Efforts should be made to grant certain rights to people living with Duchenne and Becker, or any other conditions.”

We invite you to follow his journey by following him on social media.

worldduchenne News

Organize an Event or Conference

World Duchenne Awareness Day, observed on September 7, presents a great opportunity for patient advocacy groups and patient organizations to make a significant impact. By organizing an event or conference, you can raise awareness, build a strong community, and educate key stakeholders about Duchenne and Becker muscular dystrophy (DMD/BMD). In this article, we will describe two approaches to organize an event or conference: a fun family get-together focused on community building and an educational conference, also inviting clinicians, healthcare professionals, and school teachers.

Family Get-Together for Community Building

Creating a fun and engaging family-oriented event can be an excellent way to foster a sense of togetherness within the DMD/BMD community. Don’t forget to take pictures of the day and communicate the event!

  1. Choose a Theme: Select a theme that appeals to families and your goal. Consider a superhero theme to celebrate the strength and resilience of people living with DMD/BMD, or align with the yearly WDAD theme.
  2. Fun Activities: Plan exciting activities for all ages, such as games, face painting, and interactive workshops. These activities not only entertain but also spread awareness in an enjoyable manner.
  3. Storytelling Session: Arrange a storytelling session where families share their experiences with Duchenne. This emotional connection helps build empathy and understanding.
  4. Fundraising Efforts: Organize fundraising initiatives like raffles or silent auctions to support research programs.
  5. Community Resources: Invite local support groups, therapists, and social workers to offer resources and assistance to families. Check with your local hospital if they have volunteer programs you can include in the event.

Educational Conference for Stakeholders

Consider organizing an education conference. An conference provides an opportunity to reach out to clinicians, healthcare professionals, and school teachers to disseminate knowledge about Duchenne and Becker MD.

  1. Knowledgeable Speakers: Invite experts in Duchenne research, treatment, and patient care to present the latest advancements and best practices.
  2. Breakout Sessions: Conduct focused breakout sessions to address specific concerns. These can be conversations between people living with the disease, families, clinicians, healthcare professionals, or teachers.
  3. Panel Discussions: Engage in panel discussions where people living with the disease and caregivers share their experiences, challenges, and triumphs. This personal touch fosters a deeper understanding of the condition for all attendees.
  4. Q&A Sessions: Allow stakeholders to ask questions and seek clarifications, promoting an interactive learning environment.
  5. Networking Opportunities: Facilitate networking among attendees to encourage collaborations and support networks.

Organize an Event or Conference

Organizing an event or conference for World Duchenne Awareness Day can leave a lasting impact on the community and beyond. Whether through a family day or an educational conference. Everyone can create spaces for support, education, and awareness. Together, let’s take a step forward in the journey towards a brighter future for those affected by Duchenne and Becker muscular dystrophy.

worldduchenne News

Illuminate a landmark

Illuminate a landmark for World Duchenne Awareness Day. Show your solidarity and join patient organizations in creating a wave of red light around the world. As the evening sets in on September 7, famous monuments and landmarks will be shining bright to show solidarity for the Duchenne and Becker community. Join the global movement and light up a famous landmark or monument for World Duchenne Awareness Day!

The color red

Usually, the color red will be used to create the association with World Duchenne Awareness Day. In other cases, the organization can show the logo and the signature red balloon. Next to many city halls, important landmarks can be participating. 

Illuminate a monument or landmark

What monument or landmark do you want to illuminate for this year’s World Duchenne Awareness Day? Here we are sharing success stories and guidance on how you can make this happen.

5 steps:

  1. Check the city website for procedures (office that is in charge of this activity, documents needed, timing) and write an official request (template here).
  2. As soon as you have the details from your city, contact our team and you will receive all the documents and high-resolution logos needed.
  3. Create a local communication plan to share this important action and our team will help you for the international communication.
  4. Launch your event, enjoy the light and take pictures for your memories and communication!
  5. Post your pictures on your website and social media platforms mentioning @duchenneday or @worldduchenne to share your experience with the Duchenne community.

Inspiration

  1. The Colosseum in Rome, Italy became the center piece of World Duchenne Awareness Day in Italy due to enlightening the century-old monument with the logo. Duchenne Parent Project Italy did a wonderful job!
  2. The Sagrada Família Nativity façade was illuminated in red for World Duchenne Awareness Day, with great work of Duchenne Spain.
  3. The Canadian part of the Niagara Falls was covered in a red robe to support World Duchenne Awareness Day, thanks to Defeat Duchenne Canada.
  4. In Chile, the municipality building in Santiago was illuminated in red as both DSG Duchenne and Duchenne Chile joined hands to reach out to the city mayor.

World Duchenne Awareness Day 2023 Breaking Barriers
worldduchenne Duchenne: Breaking Barriers, News

2023: Duchenne – Breaking Barriers

Official #WDAD2023 documentary

On September 7, the World Duchenne Organization launched a WDAD documentary that portrays the lives of people living with Duchenne Muscular Dystrophy across the globe and how they are each breaking barriers in their personal lives. Using storytelling techniques, the organization aims to provide insight into the barriers someone living with a rare disease may face, and provide encouraging and inspiring ways to overcome these challenges. The video is directed by Nicoletta Madia and produced by Arimvideo.

We urge everyone to share the documentary with the wider community. By working together, we can create a more inclusive and supportive society for people living with dystrophinopathies.

Theme: Breaking Barriers

The World Duchenne Awareness Day 2023 theme is ‘Duchenne: Breaking Barriers’. World Duchenne Awareness Day (WDAD) is an annual event held on September 7. With this, WDAD supports creating a society that provides equal opportunities for all. This year we organize the 10th edition.

Read full press release
See translations

Duchenne: Breaking Barriers

People living with Duchenne and Becker muscular dystrophy (DMD/BMD) face physical, healthcare and social barriers. This severely limits their ability to participate fully in community life and activities. That’s why on September 7th we call on you to take on responsibility and help break down barriers for people living with DMD/BMD. Only together as a society can we create an inclusive society and build a better future.

Some examples of topics aimed at breaking down barriers in DMD include:

  1. Access to care: Ensuring that individuals with DMD/BMD have access to comprehensive and affordable medical care to manage their condition and improve their quality of life.
  2. Accessibility: Ensuring that public spaces, such as schools, workplaces, and community centers, are accessible for people with DMD/BMD.
  3. Advocacy: Raising awareness about the challenges faced by individuals with DMD/BMD and advocating for policies and programs that promote social inclusion and equal opportunities for people with disabilities.
  4. Community engagement: Encouraging individuals with DMD/BMD to participate in community activities and providing resources and support to help them do so.
  5. Employment opportunities: Creating job opportunities for people with DMD/BMD and providing support for them to find and maintain employment.
  6. Inclusive education: Providing opportunities for people with DMD/BMD to attend mainstream schools and participate fully in the educational experience.

For inquiries, please contact Suzie-Ann Bakker, communications coordinator at the World Duchenne Organization.

How much dystrophin is needed
worldduchenne News, Women & Duchenne

#apaperaday special: How much dystrophin is needed for survival and function

Today’s pick is one of my own papers by van Putten et al in FASEB journal doi 10.1096/fj.12-224170. Here we used the fact that women/females inactivate one of their X-chromosomes to study how much dystrophin is needed for survival and function.

Low dystrophin levels increase survival and improve muscle pathology and function in dystrophin/utrophin double-knockout mice

X-inactivation also occurs in mice, normally in the 50:50 random pattern. However, there is a mouse model where the gene (Xist) coordinating X-inactivation has been altered. The chromosome with this altered Xist is more likely to be inactivated. This means that if you cross females with this Xist mutation with mdx males, the resulting female offspring will preferentially inactivate the X-chromosome with the Xist mutation and a functional dystrophin gene.

As the process is skewed but still random, this results in females expressing anywhere between 2 and 40% dystrophin in their muscles. We first did this in mdx mice, but they are only mildly affected. Here, we studied this in an mdx/utrophin knockout (dko) background, so we could also study impacts on survival.

In a first study we subjected mice to a 12 week functional test regime starting at 4 weeks of age. DKO mice (no dystrophin) generally had to be humanely killed before the age of 12 weeks. The dko/xist mice (having between 3-16% dystrophin in their muscle) survived longer. We subdivided the mice in those having <4% dystrophin and those having >4% dystrophin.

Even mice with <4% dystrophin had increased survival, lower CK and better function than dko, however mice with >4% dystrophin performed even better – though still less than wild type. We then performed a long term survival study. Notably in these studies we could only see the dystrophin levels after the animals had been sacrificed (a blinded experiment).

The 6 dko mice all died before 12 weeks, while those with <4% dystrophin survived longer. For those with 4-15% dystrophin 64% was alive at 10 months, while all mice with >15% were still alive at this point. These mice also resembled wild types in function and appearance.

6 mice were randomly selected for a very long survival study. The mice with 3% and 27% dystrophin died at 17 and 25 months due to muscular dystrophy. Other mice (>30% dystrophin) died due to age related causes >2 years old or a gall bladder problem (17 months).

Additional studies showed that dystrophin levels correlated with TIMP-1 serum levels (in mouse – we have not been able to translate this finding for patients). Also when looking at muscle histology we observed improvements at <4% dystrophin but more improvement at higher levels.

While this now may seem like old news (the paper is from 2013), it was one of the first papers showing that little bits of dystrophin already can go a long way and that it was likely not required to restore dystrophin at 20% to have a functional effect (as was the consensus at that time)

There are 3 limitations to this study however 1. The study had to use females, while Duchenne primarily occurs in men. 2. The mice had dystrophin from birth, while in patients restoration of dystrophin occurs later in life. 3. The study was in mice and not in human, so the levels may not translate directly.

Duchenne mother needs
worldduchenne News, Women & Duchenne

#apaperaday special: Needs of mothers caring for children with Duchenne

Today’s pick for the Women and Duchenne theme of World Duchenne Awareness Day focuses on female caregivers (usually mothers) of Duchenne patients and their needs. The paper is by Peay at al from the Journal of Genetic Counseling. Doi 10.1007/s10897-017-0141-4. A very important topic as caregivers often forget to care for themselves.

Psychosocial Needs and Facilitators of Mothers Caring for Children with Duchenne/Becker Muscular Dystrophy

Notably, caregivers can provide better care when their social and psychological needs are met. As such, the standards of care for Duchenne also include a ‘needs’ assessment of caregivers. These needs range from social or psychological support to e.g. cope with anxiety to financial needs and facilitating time for self-care.

Authors mention that mothers with a son with Duchenne generally adjust well and also find their caregiver experience rewarding. Here authors did a study in the aspects of lived experience of caregivers of Duchenne and Becker patients. The goal was to identify psychosocial needs, respite needs and factors that facilitate caregiving.

Authors did an online survey with 205 caregivers, all biological mothers of Duchenne or Becker patients aged 27-71. 85% had a son with Duchenne, others with Becker or an intermediate phenotype. Patients were aged 1-40 years.

Over 50% of mothers indicated a medium or high need for psychosocial support to deal with uncertainty about the future, manage fears related to Duchenne or Becker and to cope with being a mother of a son with Duchenne.

70% indicated that their child depended on care (was not independent). 21% used respite care, while 17% indicated it was too much trouble and 57% indicated they felt uncomfortable leaving the care of their son to others, while 53% indicated their son would be willing to be cared by others. 69% indicated they needed a break occasionally.

Mothers also indicated that care facilitators were their partners and extended family. When asked about self-care most indicated they exercised or had a hobby. In the discussion authors stress that mothers tend to prioritize the worries for their own child over their own needs. This means caregivers need to proactively ask about the needs for psychosocial support.

Interestingly, the needs appear to be larger for mothers with younger children – though they require less care and support. With time mothers adjust more. Authors stress that caregivers should be aware of this and proactively offer support. They speculate that a diagnostic odyssey may play a role as well with the increased worry in mothers. Earlier diagnosis might be a way to reduce anxiety.

Mothers indicated that they learned a lot from their son’s approach to life. Authors discuss limitations of the study – they recruited from a database, so this does not cover all mothers. Also, mothers who are too busy with coping, would not be able to fill out the survey.

Authors indicate that more study is needed to allow optimal care provisions for mothers with sons with Duchenne and also to study the long-term care needs. Shout out to all the mothers of sons with Duchenne for the amazing work they do!

 

Photo by Gabe Pierce on Unsplash

Duchenne manifesting carriers
worldduchenne News, Women & Duchenne

#apaperaday special: Why some Duchenne carriers have symptoms

Women and Duchenne theme continued with another paper trying to elucidate why some female carriers have symptoms and others have not. Today’s pick is from BMC medical genetics by Brioschi et al from Alessandra Ferlini’s group. Doi 10.1186/1471-2350-13-73

Genetic characterization in symptomatic female DMD carriers: lack of relationship between X-inactivation, transcriptional DMD allele balancing and phenotype

Authors introduce that it makes sense that some women have Duchenne, e.g. translocation mutations (see Sept 1 thread), or women with Turner syndrome and a dystrophin mutation (Turner patients have only 1 X-chromosome), or women who have two mutated dystrophin genes.

However, carriers have one functional and one mutated dystrophin gene. Authors wanted to elucidate why some carriers manifest symptoms, while others do not. They studied 7 manifesting and 11 non-manifesting carriers.

All 18 women had elevated CK levels, while the 7 manifesting carriers also had muscle weakness and pain with an age of onset of 2-43 years. None of the 18 women had heart pathology.

Staining of muscle biopsies showed a mosaic dystrophin pattern for both manifesting and non-manifesting carriers as well as signs of muscle damage and regeneration.

Authors then looked at X-inactivation patterns in the muscle biopsy. They used a proxy marker for this, the androgen gene (also located on the X-chromosome). In addition, they studied how much dystrophin was expressed from each of the two genes (so mutated and functional transcripts).

Interestingly, there was little correlation between X-inactivation and how much dystrophin was expressed from each gene. This suggests that skewed X-inactivation is not a likely cause of manifesting symptoms for carriers.

Authors note that for the 1 patient with the most severe symptoms, dystrophin levels were very low, while they were higher for an asymptomatic carrier. However, they performed this analysis only for these 2 individuals so it is premature to really draw strong conclusions.

It is good that authors looked at X-inactivation patters in muscle rather than blood (as is often done). However, the pattern in one piece of one muscle may still not be reflective of all the muscles. There is no way around this problem so authors did as well as they could.

Unfortunately, while the paper reveals that skewed X-inactivation is likely NOT to underly the manifesting of symptoms for patients, it does not reveal what IS the cause. Sadly, this is still unknown.

Manifesting Duchenne carriers
worldduchenne News, Women & Duchenne

#apaperaday special: Cause of manifesting Duchenne carriers

Today and tomorrow we dive into the cause of manifesting carriers starting with a paper by Soltanzadeh et al in Neuromuscular Disorders. Doi 10.1016/j.nmd.2010.05.010

Clinical and genetic characterization of manifesting carriers of DMD mutations

While most women who have a mutation in one of their dystrophin genes do not have symptoms, 2-8% does present with symptoms. The severity of these symptoms varies and they involve mainly muscle weakness and pain. For some manifesting carriers, the severity can be almost as severe as Duchenne.

Two days ago I explained about X-inactivation: when the embryo is in a ~100 cell stage either the X-chromosome of the mother or that of the father is randomly inactivated in each of the cells and that inactivation pattern is then inherited by all daughter cells.

This means that carriers will have ~50% of muscle fibers that express dystrophin (mutated dystrophin gene inactive) and 50% of muscle fibers that do not express dystrophin (functional dystrophin gene inactive).

That is indeed what one sees when a biopsy of a female carrier is stained for dystrophin. Furthermore, some pathology is generally also visible: variation in muscle fiber size, centrally located nuclei (sign of recent regeneration) and damage/necrosis and inflammation.

In this paper authors studied how often manifesting carriers occurred in their database. Out of 860 female subjects, 15 manifesting carriers were identified (weakness and myalgia). 8 had a relative with Duchenne, while 7 did not. Of the 15, 5 had dilated cardiomyopathy (DCM).

Yesterday I stressed that carriers are at risk for developing DCM in the absence of muscle symptoms. When carriers manifest muscle symptoms, the risk of also developing DCM increases.

Authors analyzed biopsies of some of the manifesting carriers and confirmed they had the pathological signs expected. Also the mosaic dystrophin staining pattern was observed.

Authors looked into reasons why these carriers manifested symptoms. For 1 the reason was clear: she carried two mutations in the dystrophin gene – likely one on each of her dystrophin genes. This was a woman who was quite severely affected, as would be expected.

For the other carriers authors speculated X-inactivation might have been skewed. Because the process is random it is possible that instead of 50:50, an 80:20 pattern occurs (or 70:30 etc). When the functional gene is inactivated with a higher frequency than the mutated gene, less dystrophin can be produced is the hypothesis.

Authors looked at X-inactivation in the blood cells of the carriers and found that for 5 manifesting carriers, X-inactivation was skewed while for others it was not. Note that it is possible the X-inactivation patters between muscle and blood cells varies, so their results may not have been predictive for muscle in all cases.

The most important lessons from this paper are that dilated cardiomyopathy is frequent in manifesting carriers. Clinicians should be aware of this. Secondly, women can be a carrier of the dystrophin mutation and manifest symptoms also if they do not have a relative with Duchenne.

In fact, about 50% of the cases discussed here did not have a relative with Duchenne. This resulted in delays in identifying the cause of the symptoms. In fact, one of the women underwent a liver biopsy because her transaminase enzymes were elevated.

These enzymes occur in liver but also in muscle and will leak into blood upon damage of either.

This paper underlines that awareness of women with dystrophin mutation being at risk for heart and muscle pathology is important to initiate genetic counseling and but also to prevent incorrect medical intervention and allow proper medical intervention.