Making sense of genetic testing: The importance of a genetic diagnosis in DMD – Hear from our expert

Are you aware of the diagnostic techniques available for making a genetic diagnosis for children with suspected Duchenne muscular dystrophy (DMD)? Do you know about the critical importance of identifying the specific mutation?

Underscoring the importance of mutation types, Dr Aartsma-Rus discusses key steps for the early diagnosis of DMD. Mutations in the DMD gene eliminate or diminish dystrophin function, causing DMD and Becker muscular dystrophy (BMD; a milder inherited progressive muscle-wasting condition).1,2 As such, establishing a genetic diagnosis is critical for confirming diagnosis of DMD.

Watch now to find out more about the:

  • Disease continuum of DMD and the progressive loss of functionality  
  • Frequency and effect of different types of DMD-causing mutations on the dystrophin transcript
  • Distinctions between mutations found in BMD and DMD
  • Techniques available for making a genetic diagnosis for children with suspected DMD
  • Importance of having a specific genetic diagnosis in the context of disease prognosis and genetic counselling 

Prof. Dr. Annemieke Aartsma-Rus, Professor of Translational Genetics at Leiden University Medical Center (LUMC), the Netherlands, discusses the importance and methods of obtaining an early and accurate genetic diagnosis for DMD. She has played an important role in the development of antisense-mediated exon-skipping therapy for DMD during her PhD research at the Department of Human Genetics of the LUMC. In 2007, she became Group Leader of the Duchenne exon-skipping group. Since 2013, she has a visiting professorship at the Institute of Genetic Medicine of Newcastle University (UK).

Genetic testing is the only way to diagnose DMD. If you want to know more, click here.

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Signs and symptoms of Duchenne muscular dystrophy (DMD)

Dr. Luca Bello discusses the importance of early diagnosis of DMD and how to recognise the early signs and symptoms (muscle weakness, not walking by 16-18 months, calf hypertrophy, cognitive and speech delay). If you suspect DMD, perform a creatine kinase (CK) test.

Click here to check the red flag signs and symptoms. If you suspect Duchenne muscular dystrophy, perform a creatine kinase (CK) test. Click here to learn more.

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Parent’s perspective: my wonderful Duchenne son

Never will I forget the sunny day in March, many years ago, when the paediatrician announced: “Your son has a serious, incurable muscle disease.” He looked at me cautiously, as if waiting for a reaction. A sign that I understood what he had just said.

But there was nothing. My head was fuzzy.

I sat there numb, and had no idea how to start getting my head around this word. I just couldn’t grasp it. But two thoughts crossed my mind.

Was this man off his head giving me such a terrifying diagnosis after just watching my son stand up once? At the same time the thought came: of course, he’s right, and I knew it!

Despite all the reassurance from doctors, physiotherapists and other people, I had always suspected that something was wrong. If I were not so shocked, I might have felt a fleeting sense of satisfaction. Finally, I was no longer the neurotic mother who was always imagining things.

Why my child?

A dark time followed that fateful March day. For days I felt like I was in freefall. Not once was I able to remember the words ‘muscular dystrophy’, because my consciousness refused to accept this diagnosis. All I could think about was that my barely five-year-old, innocent, blonde, curly-haired boy would die of this disease. That thought ripped my heart out.

Why my child? As hard as it was, I kept asking myself the same question. I quarrelled with God and the world – especially with God. What had I done to deserve this? What had my child done? I looked for answers in religion, read books on coping strategies, and looked for advice from other parents of ‘special’ children, gradually learning to give up meaningless and difficult questions.

I decided that despite this devastating diagnosis, we would have a good life

Naturally, my little boy did not suspect what was going on, and his older sister went about her life. That was maybe my salvation: I was forced to carry on as normally as possible. After a few weeks this hard time ended and I began to deal with the illness. I spoke to the nursery, primary school, friends and neighbours. I turned to the church and I researched self-help groups. Sometimes I had to swallow a lot but the more I talked about the disease, the easier it became for me. I decided that we would have a good life despite this devastating diagnosis. The idea of life expectancy faded into the background and disappeared for many years. I stopped searching for research and concentrated on life instead.

Important decisions had to be made again and again. Which school is suitable? How would he get on there? Does he need a teaching assistant, or could he manage without? How will I deal with the topic of school trips? Will he be bullied? Should he take steroids or not? How can I tell him why he is so different from his friends? How do I find the right words?

When will he need a wheelchair? How can we deal with the situation as a family? Will I be able to do justice to his sister? Many sleepless nights came and went, and it was always my son who gave me courage and strength.

Naturally our life was very different to those of our family, neighbours and friends, simply because we thought differently.

Completely and naturally, he accepted his fate

My son went to the only local primary school along with his friends, unfortunately on a hill. Sending him to the nearest special school would certainly have made many things easier, but I didn’t feel he belonged to that world yet. The children in his class were totally at ease with him and the school went out of their way to make school trips manageable. He felt fine, was almost always in good spirits and carried on like a normal person. The moments when he was sad or stressed were rare and never lasted long.

As he got older he started to think about his situation. He kept his thoughts to himself. Text books say you should only answer the questions your child asks. But he did not ask questions. He seemed to sort things out on his own. Without any fuss, he just seemed to accept his fate. I was worried because for a long time I thought he needed to know what was the matter with him. But I found out many years later that he had in fact known for a long time, but just didn’t talk about it. Still, I felt it was time to put my son in touch with other children with Duchenne. So, in the hot summer of the football world championship in Germany, we drove to a rehabilitation clinic in Weserbergland for the first time.

I was surprised to discover how relaxed and happy the mood was between the parents and children; even families with older boys were having fun. I was even more surprised that we became part of a big family. To this day, our rehabilitation stays in Hoxter are one of the highlights of the year.

His illness always gave me the time to grow into it and keep up

And so the years went by. There were several surgeries and long hospital stays. The need for financial assistance steadily increased, there were many battles with health insurance, and there was always the ongoing worry about his health, his muscle loss and loss of function, ventilation and heart medication.

I watched his playmates progressing while he went backwards, and that hurt a lot. On the other hand, I learned to live in the present – a skill I had always wanted. His illness always gave me the time to grow into it and keep up. I grew into it and made my peace with Duchenne.

Today my son is a smart, polite and, above all, compassionate person who always makes me laugh with his dry humour. He is a gift: my wonderful Duchenne son!

Click here to find out what you can do help to achieve the correct diagnosis and bring reassurance to families.

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Reaching a Duchenne muscular dystrophy (DMD) diagnosis from an initial suspicion of the condition

Suspicion of DMD – next steps for diagnosis

Watch this video to hear from Dr. Luca Bello, Physician Neurologist from Padova, Italy discussing the diagnostic journey for a DMD patient. Starting with a creatine kinase (CK) test to the importance of an accurate diagnosis through genetic testing to enable the correct medical management options to be identified.

Don’t wait to investigate suspicions of Duchenne muscular dystrophy. Order a CK test, elevated CK levels should prompt referral to a neuromuscular specialist for further testing.

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What are the early signs and symptoms of Duchenne muscular dystrophy?

The onset of symptoms occurs in childhood.1 Delayed motor milestones are the most noticeable signs in early childhood. Key symptoms can include:2
  • Delayed motor development2
  • Difficulty rising to stand or not walking well by 18 months1,3
  • Delayed speech and/or cognitive delay2

How a DMD child might rise from the floor: Gowers’ manoeuvre4–6

The difference in calf muscles of a healthy boy versus a boy with DMD

PTC has the right to distribute this image in perpetuity.

Recognising red flag signs and symptoms

Developmental delay should trigger a creatine kinase (CK) test2,3

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What kind of disease is Duchenne muscular dystrophy?

Duchenne muscular dystrophy (DMD) is a rare genetic disorder that causes progressive muscle damage and degeneration.1,2 It is the most common and severe form of muscular dystrophy among children, and accounts for over 50% of all cases.3 It is caused by a mutation in the dystrophin gene which leads to the absence of, or defects in, dystrophin – an essential protein in the muscle cell membrane.1,4

Duchenne is characterised by progressive decline in muscle function, leading to loss of ambulation and respiratory and cardiac failure1,2

Children with Duchenne suffer with progressive muscle deterioration and an ongoing decline in physical function.5

Muscle weakness becomes apparent in early childhood, and, on average, patients require a wheelchair by the early teenage years.3,5,6

Ultimately, progressive muscle degeneration causes respiratory and cardiac failure, leading to early death.1

Early intervention may improve patient outcomes1,2

  • Once muscle is lost it cannot be restored9, 10
  • Early diagnosis is critical to gain access to the right treatments and services1,2,11
  • The role of primary care is vital as they are in an ideal position to spot early signs of neuromuscular disease, and therefore make a timely referral2,11,12
Timely and accurate diagnosis can enable the patient and family to receive the care and support they need1,2,13

Duchenne muscular dystrophy is a severe progressive disease presenting in early childhood that needs an accurate and early diagnosis.1 Learn how to recognise the early signs and symptoms, click here.

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What is muscular dystrophy?

The muscular dystrophies are a group of neuromuscular disorders characterised by progressive muscle degeneration and weakness.1 They are caused by mutations in genes that produce either dysfunctional, or insufficient levels of, proteins that are essential for muscle cell stability.1 Children with muscular dystrophy experience progressive muscle deterioration and an ongoing decline in physical function.1

There are different forms of muscular dystrophy2

The muscular dystrophies differ in age of onset, severity, pattern of inheritance, and the muscle groups and other organs affected.1


Duchenne2,3
Duchenne is the most common and severe form of muscular dystrophy among children, and accounts for >50% of all cases. It primarily affects males.


Becker2,3
Becker is less common and severe than Duchenne but presents with similar symptoms.


Myotonic2
Myotonic is the most common adult form of muscular dystrophy.


Congenital2
Congenital muscular dystrophy appears at birth or by age 2.


Emery-Dreifuss2
Emery-Dreifuss primarily affects boys, with symptoms usually apparent by age 10.


Facioscapulohumeral (FSHD)2
FSHD refers to the areas affected – the face (facio), shoulders (scapulo) and upper arms (humeral). It typically affects adolescents.


Limb girdle2
Most often appears in adolescence or young adulthood. Affects both males and females.


Distal2
Distal muscular dystrophy is less severe and progresses more slowly than other forms of muscular dystrophy. It typically appears at 40–60 years of age.


Oculopharyngeal2
Oculopharyngeal muscular dystrophy occurs in both men and women, typically in a person’s 40s or 50s. It can be mild or severe.

Learn how to recognise neuromuscular disorders, click here to access the RCPCH e-learning module.

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What are neuromuscular disorders?

Neuromuscular disorders encompass a wide range of diseases that affect the voluntary muscles and the nerves that control them.1

They are generally classified depending on the location of involvement, and include:1

Disorders of the muscle (e.g. Duchenne muscular dystrophy)

Disorders of the neuromuscular junction (e.g. congenital myasthenic syndrome)

Disorders of the motor neuron (e.g. spinal muscular atrophy)

Disorders of the peripheral nerve (e.g. Charcot-Marie-Tooth disease)

The majority of neuromuscular disorders that present in childhood have a genetic basis.1 The most commonly encountered genetic paediatric neuromuscular condition is Duchenne muscular dystrophy, which affects 1 out of every 3,600–6000 newborn males worldwide.1-4

What are the signs and symptoms of neuromuscular disorders?

Children with neuromuscular disease experience progressive muscle deterioration and an ongoing decline in physical function.5 The earliest and most common sign of neuromuscular disease is muscle weakness, which manifests as delayed motor development.4,6 Delays in language, speech and cognition should also prompt suspicion that something may be wrong.4,7–9 To learn more about red flag signs and symptoms click here.

Monitoring motor development can help to identify developmental delay earlier, allowing for timely referral to aid the diagnostic process.7

Why early diagnosis matters

Even though neuromuscular diseases are not curable, management and treatment options are available. 10,11

An early diagnosis can facilitate access to the right treatment and services, which may help improve outcomes and help to avoid life-threatening complications. 4,6,10

An early diagnosis can help improve outcomes and avoid life-threatening complications4,6,10 If you suspect a neuromuscular disorder, order a creatine kinase (CK) blood test, click here to learn more.

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The Duchenne muscular dystrophy (DMD) journey: from symptom onset to management

From the recognition of symptoms to treatment and supportive care, there are multiple stages in the management of a patient with DMD.

In this video, Paediatric Neurologist Dr. Damjan Osredkar discusses his centre’s experience in the diagnosis and management of Duchenne. He also describes the benefits of a multidisciplinary care team and explains why it is important to have an individualised DMD care plan.

Click here to learn more about diagnosis and management of Duchenne muscular dystrophy

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Carrier screening for Duchenne muscular dystrophy (DMD): why is it important and who is eligible?

Early detection means that women who are carrying the DMD mutation can:

  • Be offered genetic counselling, which can inform them about the risks of transmitting the mutated allele in future pregnancies2
  • Have the option of prenatal genetic testing2
  • Be made aware of alternative reproductive options, such as the use of donor eggs or human assisted reproduction with preimplantation genetic diagnosis (PGD)2
  • Undergo regular surveillance for cardiomyopathy from early adulthood5
  • Receive early cardiac treatment if heart involvement is detected3,4

Who is eligible for carrier analysis?

Family members of an individual with DMD should receive genetic counselling to establish who is at risk of being a carrier.1

Carrier genetic testing should be performed in female relatives of a boy or man who has been genetically confirmed to have DMD.1

Carrier testing may help reduce the transmission of Duchenne muscular dystrophy and improve outcomes for women at risk.1-4 Click here for the 2018 Duchenne Care Considerations.

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The importance of early diagnosis

While there is no cure for Duchenne muscular dystrophy, studies have shown that early diagnosis and care can help slow DMD progression and minimise the risks and complications of the disease.1-5

This means that patients may:1,2,5-8

stairs

Remain ambulatory for longer

lungs

Preserve their pulmonary and cardiac function longer

Have a better quality of life

Live Longer

It also means:

  • Parents of patients can have earlier access to genetic counselling, which can assist with family planning2
  • It may be possible to enroll the child in research-based registries and clinical trials of investigational treatments2

Your role in detecting DMD has never been more important

Prompt intervention is critical to help delay disease progression and help preserve muscle function for as long as possible.

Early diagnosis and care can help slow Duchenne muscular dystrophy progression and minimize the risks of complications of the disease.
If you see signs and symptoms of Duchenne muscular dystrophy, order a creatine kinase (CK) test – click here to learn more

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Duchenne muscular dystrophy is a progressive disease presenting in early childhood that needs an accurate and early diagnosis

Once muscle is lost, it cannot be restored.1–3 Therefore, early testing and diagnosis are critical to gain access to the right treatments and services1,4-6

The timeline provides a summary of key motor and non-motor developmental milestones that may be missed in a child presenting with a neuromuscular disorder and children with Duchenne muscular dystrophy.

Recognising red flag signs and symptoms

Children with developmental delays or other signs of Duchenne muscular dystrophy should have a creatine kinase (CK) test
For more information about CK testing, click here

 

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Online resources

DMD information booklet

A guide for patients, parents and caregivers.

Treat DMD Resource

The Guide for Families, can be downloaded from www.treat-nmd.org. This guide contains all the latest information on how Duchenne is diagnosed, how it progresses and the types of support and care you and your family will receive to help you through this journey.

Physiotherapy exercise book (younger children)

This pack contains information on how to perform some
of the stretches your physiotherapist has recommended
for younger children.

Physiotherapy exercise book (older children)

This pack contains information on how to perform some
of the stretches your physiotherapist has recommended
for older children.

Postural management and stretches

Information for adults with Duchenne muscular dystrophy on postural management and stretches.

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Duchenne muscular dystropy (DMD): What is it and how is it managed?

From the recognition of symptoms to management and supportive care, there are multiple stages in the management of a patient with DMD.

In this video, Prof. Ros Quinlivan from the National Hospital for Neurology and Neurosurgery in London, UK describes the early key signs and symptoms that would trigger a suspicion and further testing. She also describes the progressive nature of the disease and discusses her centre’s experience in the management of patients with DMD.

This video is based on professional and expert opinion of Prof. Ros Quinlivan.

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Genetic testing for Duchenne muscular dystrophy

Genetic testing is the only method for determining a patient’s specific mutation type.1,2 This is important because a specific genetic diagnosis may help identify medical management options and potential to enrol into clinical trials.2

Additionally, once a mutation is identified, female relatives can find out their carrier status. This is important for two main reasons:2

number 1

Female carriers can pass on Duchenne muscular dystrophy to their children

number 2

Female carriers need medical assessment and follow-up

A genetic diagnosis involves two types of tests

First-level testing1,3
  • The majority of mutations (~70%) are detected by multiplex ligation-dependent probe amplification (MLPA)
  • MLPA can detect both large deletions and large duplications in patients and carriers
Second-level testing1
  • If no mutation is found, gene sequencing should be performed
  • Only gene sequencing can definitely detect smaller mutation types. These mutations include point mutations (nonsense or missense), small deletions, and small duplications or insertions

How to accurately diagnose Duchenne muscular dystrophy1,2

Adapted from references 1, 4 and 5

Genetic testing is the only way to determine the specific mutation causing Duchenne muscular dystrophy and could help patients get on the right treatment pathway1,2

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What is creatine kinase (CK)?

Creatine kinase (CK) is an enzyme found in skeletal muscle as well as in the heart, brain and other tissues. Increased amounts of CK are released into the blood when there is muscle damage.1 Elevated CK levels reflect muscle damage in patients with Duchenne muscular dystrophy, making it an important diagnostic marker for the condition.2

When to order a CK test

A CK test should be carried out if:

  • Examination and medical history suggest progressive muscle weakness1,3,4
  • A child has delayed motor function, such as not walking well or not able to rise to stand by 18 months1,3,5,6
  • A child shows developmental delay, including delays with mixed presentation (e.g. speech and cognition), and evaluation suggests a peripheral neuromuscular problem3
  • A child has a positive family history of Duchenne muscular dystrophy and suspicion of abnormal muscle function6
  • Blood tests reveal an unexplained increase in transaminases6

What the results mean1,6

IF CK IS ELEVATED
(Normal range is generally up to 250 U/L*)1
Refer to neuromuscular specialist for Duchenne muscular dystrophy gene testing6
IF CK IS NORMALDoes not rule out other neuromuscular disorders1

Developmental delay should trigger a CK test

Normal or mildly elevated CK levels do not rule out neuromuscular disease1

*The normal CK range is generally up to 250 U/L. Absolute values may differ between laboratories.1

Prompt CK testing can help to achieve the correct diagnosis and bring reassurance to families1,9

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Children with developmental delays should have a creatine kinase (CK) test

If a child is failing to meet developmental milestones, it could be due to a neuromuscular disorder.1,2 Primary care physicians are ideally placed to recognise the early signs and symptoms of neuromuscular disorders, so that children can be referred to a neuromuscular specialist without delay.1,2 To check the red flag signs and symptoms click here.

If you suspect a neuromuscular disorder, order a CK blood test.1
• Elevated CK levels reflect muscle damage, and are a sign of certain neuromuscular disorders1–5
• A CK test is quick, simple and inexpensive1,3,6

A CK test should be carried out if:

  • Examination and medical history suggest progressive muscle weakness7-9
  • A child has delayed motor function, such as not walking well or not able to rise to stand by 18 months2,7,8,10
  • A child shows developmental delay, including delays with mixed presentation (e.g. speech and cognition), and evaluation suggests a peripheral neuromuscular problem7
  • A child has a positive family history of Duchenne muscular dystrophy and suspicion of abnormal muscle function2
  • Blood tests reveal an unexplained increase in transaminases 2

Refer all patients with elevated CK levels or missed motor milestones8,11

All patients who have elevated CK levels should be promptly referred to a neuromuscular specialist.8,11

Normal or mildly elevated CK does not rule out neuromuscular disorder. If a patient has missed motor milestones, they should also be referred to a neuromuscular specialist.8

Prompt referral is vital to give your patients the best chance of better outcomes1,2

A neuromuscular specialist can then:2

Identify the child’s exact mutation2
Confirm Duchenne muscular dystrophy with a genetic diagnosis and identify the specific mutation causing the disease2

Define best management options2
Decide upon appropriate treatment and interventions to help delay disease progression2

Developmental delay should trigger a CK test

Prompt CK testing can help to achieve the correct diagnosis and bring reassurance to families.3,13 Learn more about CK testing here.

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E-learning for healthcare professionals

Interested in learning more on neuromuscular disorders?
Read below to access an e-learning module developed by the Royal College of Paediatrics and Child Health (RCPCH) in the UK.

eLearning Module – Spot the early signs

Recognising neuromuscular disorders – A practical approach

Children with neuromuscular disease experience progressive muscle deterioration and a continual decline in physical function.1 Signs and symptoms usually begin in early infancy, but it can take a long time before a child is diagnosed.1,2 This means missing out on early treatments and interventions that can significantly improve these young patients’ futures.

This eLearning module will help you recognise the early signs of muscle disease so you can refer your patients with confidence.

  • Developed by experts at Newcastle Muscle Centre and Newcastle University in collaboration with the Royal College of Paediatrics and Child Health (RCPCH)
  • Free to take
  • Only takes an hour to complete
  • CME accredited in the UK

This eLearning module has been supported by a financial grant from PTC Therapeutics. PTC Therapeutics have had no involvement in the development of the content of this module.

Access the e-learning module and select the course ‘Recognising Neuromuscular Disorders’.

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Upcoming international meetings and events

Rare Disease Day

28 February 2021

Rare Disease Day, coordinated by EURORDIS, takes place on the last day of February each year. The main objective of Rare Disease Day is to raise awareness amongst the general public and decision-makers about rare diseases and their impact on patients’ lives. Find out how you can get involved here https://www.rarediseaseday.org/

16th International Congress on Neuromuscular Diseases (ICNMD)

21-22 May & 28-29 May 2021
Valencia, Spain

ICNMD conference brings together a diverse group of clinicians, scientists, students and industry professionals around the world invoved in field of Neuromuscular diseases. The conference is organised on behalf of the Neuromuscular Disorders Applied Research Group of the World Federation of Neurology. For more information visit their website https://icnmd.org/

10th Europaediatrics Congress:

7 – 9 October 2021
Zagreb Croatia

The congress brings together paediatricians and child health professionals working in primary, secondary and tertiary care across Europe and internationally focused on health promotion and prevention of disease and disability as well as to optimize the health and wellbeing of the child and family. For more information visit https://www.europaediatrics2020.org/en

7th Congress of the European Academy of Neurology (EAN)

19-22 June 2021
Vienna, Austria

EAN is an annual congress that brings together neurologists not only from Europe, but from all over the world. The overarching theme for the 2021 congress is ‘Towards Precision Neurology’. For more information visit https://www.ean.org/congress-2021

26th International Annual Congress of the World Muscle Society (WMS)

20-24 September 2021
Prague, Czech Republic

The Annual Congress of the World Muscle Society (WMS) is an annual international Congress focused on the field of neuromuscular disorders. For more information visit https://www.wms2021.com/

World Duchenne Awareness Day

7 September 2021

World Duchenne Awareness Day is a global day that aims to raise awareness of Duchenne and support those affected by the condition. Join patients, families, Duchenne experts and other organisations in advocating for improved access to care, research and education. https://www.worldduchenneday.org/

14th European Paediatric Neurology Society Congress (EPNS)

28 April – 2 May 2022
Glasgow, UK

The EPNS Congress is one of the largest gatherings of paediatric neurologists worldwide and provides an opportunity to learn about the latest developments in the rapidly evolving field of child neurology. For more information visit https://epns-congress.com/

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Educational materials for children and caregivers

These printable educational materials, presented in a comic book style, explain Duchenne muscular dystrophy in a highly visual and easy to understand way and are suitable for different age groups. These have been developed and funded by PTC Therapeutics.
Click the images to download printable PDFs.

Share these useful resources with your patients and their families

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Duchenne patient websites

Duchenne and You patient website

Developed specifically for patients and caregivers, Duchenne and You helps patients and their families understand the basics about Duchenne muscular dystrophy, how it affects the body and why intervention is important. It also provides support and information to help make living with Duchenne muscular dystrophy that little bit easier. Duchenne and You has been developed and funded by PTC Therapeutics.

www.duchenneandyou.eu

TREAT-NMD website

TREAT-NMD is a global academic network that focuses on advancing research in neuromuscular disorders. The TREAT-NMD website provides a wealth of information on neuromuscular diseases, including best practice care, expert advice, patient registries and disease information.

https://treat-nmd.org

The World Duchenne Organisation (WDO)

The World Duchenne Organisation (WDO) is an advocacy group organisation set up by parents and families of those with Duchenne muscular dystrophy around the world.

https://worldduchenne.org/



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Key Duchenne muscular dystrophy (DMD) publications

In this section you will discover a selection of published journal articles from DMD scientific and clinical research.

Life expectancy of patients with DMD: 2020 systematic review and meta-analysis

A systematic review and meta-analysis that reviewed the body of published literature on life expectancy at birth in DMD, providing HCPs with an update regarding current prognosis for survival. Landfeldt E, et al. Eur J Epidemiol. 2020;10.1007/s10654-020-00613-8. https://link.springer.com/article/10.1007/s10654-020-00613-8

How to reduce the time to DMD diagnosis: 2019 expert consensus

This review and expert consensus provides clear recommendations on the steps required to reach a complete diagnosis of DMD. Aartsma-Rus A, et al. J Pediatr. 2019;204:305. https://www.jpeds.com/article/S0022-3476(18)31550-6/fulltext

International standard of care guidelines for the diagnosis & management of DMD

2018 update to the 2010 Duchenne Care Considerations outlines the latest in clinical care to help families and healthcare professionals manage DMD. The guidelines represent international consensus on the optimal diagnosis and management of DMD, offering guidance on assessments and interventions for the manifestations and secondary complications of the condition.
Part 1    Birnkrant DJ, et al. Lancet Neurol. 2018;17:251–267
Part 2    Birnkrant DJ, et al. Lancet Neurol. 2018;17:347–361
Part 3    Birnkrant DJ, et al. Lancet Neurol. 2018;17:445-455
http://www.treat-nmd.eu/care/dmd/diagnosis-management-DMD/

Duchenne Care Considerations: a guide for families

Published in 2018, this guide summarises the 2018 Duchenne Care Considerations in language that is accessible for patients and their families. It aims to give patients, families and caregivers access to the information necessary to enable them to work with their healthcare team in delivering optimal DMD care. The guide is also available in various languages. http://www.treat-nmd.eu/care/dmd/family-guide/translations/

The importance of genetic testing for DMD: diagnosis, genetic therapies and implications for family members

This review discusses different mutations causing DMD, how to establish a genetic diagnosis, and the importance of having a specific genetic diagnosis in the context of emerging genetic therapies. Aartsma-Rus A, et al. J Med Genet. 2016;53:145–151. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4789806/

Infant screening for DMD

This review article presents a two-step CK-DNA pilot screening programme for DMD, which aims to improve rates of screening in infants to facilitate earlier diagnosis. Vita GL, Vita G. Neurol Sci. 2020;10.1007/s10072-020-04307-7. https://www.ncbi.nlm.nih.gov/pubmed/32112218

Check out the meetings and events section for upcoming international (or local) congresses and events

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Duchenne muscular dystrophy materials

The following materials are intended for healthcare professionals. These materials have been developed and funded by PTC Therapeutics.
Click on the images to view the PDFs.

International Duchenne Care Consideration infographics

international duchenne are consideration info

Why a creatine kinase (CK) test?

What to do if you suspect Duchenne muscular dystrophy

The importance of genetic testing

Patient case study – Diagnosis of Duchenne muscular dystrophy (DMD) in an 8-year-old boy

Patient case study – diagnosis of Duchenne muscular dystrophy (DMD) in two brothers

Click to download the materials.

For more information about Duchenne muscular dystrophy contact us at info@takeonduchenne.eu

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Expert insights

The following materials are intended for healthcare professionals. These materials have been developed and funded by PTC Therapeutics.

Signs and symptoms of Duchenne muscular dystrophy (DMD)

Physician Neurologist Dr. Luca Bello explains the importance of early diagnosis and key signs and symptoms to look out for in DMD.

Suspicion of Duchenne muscular dystrophy (DMD)

Dr. Luca Bello describes the key steps in reaching a DMD diagnosis from an initial suspicion of the condition.

Duchenne muscular dystrophy (DMD): From signs and symptoms to management

Paediatric Neurologist Dr. Damjan Osredkar discusses his centre’s experience in the diagnosis and management of DMD. He also describes the benefits of a multidisciplinary care team and explains why it is important to have an individualised DMD care plan.

Duchenne muscular dystrophy (DMD): What is it and how is it managed?

Prof. Ros Quinlivan from the National Hospital for Neurology and Neurosurgery in London, UK describes the early key signs and symptoms that would trigger a suspicion and further testing.

Read more on how you can help aid recognition and diagnosis of Duchenne muscular dystrophy

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International Duchenne Care Considerations summaries

PTC have developed these focused, two-page summaries to provide you with a digestible overview of the 2018 International Duchenne Care Considerations. Click on the summaries to view.

Diagnosis and management of Duchenne muscular dystrophy – Part 1
Diagnosis and management of Duchenne muscular dystrophy – Part 2
Diagnosis and management of Duchenne muscular dystrophy – Part 3

Access the full International Duchenne Care Considerations here.

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Pharmacological therapy: Learn more about treatment with glucocorticoids

Along with physiotherapy, treatment with glucocorticoids remains a mainstay of Duchenne muscular dystrophy treatment and it is recommended that individuals should continue taking glucocorticoids after loss of ambulation.1

Recent studies have also demonstrated the benefits of early glucocorticoid treatment, before significant physical decline.1-3

The long-term effects of glucocorticoid therapy have been shown to include*:

muscle

Preserved muscle strength and motor function4,5

stairs

Delayed loss of ambulation1,4

lungs

Preserved pulmonary function1,4,5

spine

Avoidance of scoliosis surgery1,4,5

Improved survival4

*compared to untreated patients

The 2018 International Care Guidelines recommends following an initial consultation with the family, a discussion regarding side effects and a nutritional consultation should occur before any glucocorticoid treatment is initiated.1 Well documented side effects of long-term corticosteroid use can include; weight gain and obesity, acne and warts, cushingoid features, growth retardation and delayed puberty, cataracts, immune/adrenal suppression, glucose intolerance, hypertension, adverse behavioural changes, gastro-oesophageal reflux, peptic ulcer, gastritis, osteoporosis and myoglobinuria.6

Click here for the International Duchenne Care Considerations summaries.

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Pharmacological treatments for the management of Duchenne muscular dystrophy (DMD)

There are different approaches to pharmacological management:

muscle

Glucocorticoids, a mainstay therapy, for the treatment of muscle strength and function1,2

Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) for the treatment of heart disease3

spine

Bisphosphonate therapy for the treatment of osteoporosis3

Hormone replacement therapy for the treatment of impaired growth, delayed puberty, and adrenal insufficiency1

Additional therapeutic strategies:*4

DNA helix

Mutation-specific therapies or gene replacement therapies aiming to restore dystrophin production

DNA helix

Muscle membrane stabilisation and/or upregulation of compensatory proteins which are structurally and functionally similar to dystrophin

DNA helix

Reduction of the inflammatory cascade and/or enhancement of muscle regeneration

*Some of these treatments have been approved by regulators while others are near, or in regulatory review or in clinical trials and might become available in the future1,4

Duchenne International Care Considerations highlight that physiotherapy and glucocorticoids remain the mainstays of treatment for Duchenne muscular dystrophy – click here to learn more.

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How genetic mutations cause Duchenne muscular dystrophy (DMD)

Approximately one-third of DMD cases are thought to arise because of de novo mutations, with the remaining two-thirds of cases inheriting the mutation from carrier mothers.1,2

How is DMD inherited?

DMD is inherited in an X-linked recessive pattern. Since males have only one X chromosome, a mutation in the gene responsible for DMD is sufficient to cause the condition.4

Females have two X chromosomes, so a mutation would have to occur in both copies of the gene responsible for DMD to cause the disorder.4

In X-linked recessive inheritance, a female with one mutated copy of the gene can pass it on to her children. Every son and daughter of a female carrier has a 50% chance of inheriting the faulty gene. Sons who inherit the faulty gene will have DMD, while daughters will be carriers.4

DID YOU KNOW: Duchenne muscular dystrophy is inherited in an X-linked recessive pattern4

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The dystrophin gene

The dystrophin gene is located on the X chromosome and is the largest gene in the human genome.1 This may make it more susceptible to mutations.2 So far, more than 7,000 individual mutations in the dystrophin gene have been identified.1

Dystrophin gene mutations

Deletion, duplication, point and other small mutations can cause Duchenne muscular dystrophy1,3,4

Why mutation type matters

Knowing the mutation type can be helpful for medical management options, and the possibility of enrolling into clinical trials.4,5

Large mutations can be detected using multiplex ligation-dependent probe amplification (MLPA). Small deletions, such as nonsense mutations, require gene sequencing. 4

Adapted from references 1, 3 and 4. 

Only genetic testing can identify the dystrophin gene mutation type; this is important for genetic counselling, prenatal diagnosis and considering mutation-specific therapies

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What causes Duchenne muscular dystrophy?

Mutations in the dystrophin gene lead to the absence of, or defects in, dystrophin – an important component of the muscle cell membrane.1,2

Dystrophin is an important component of the muscle cell membrane1

Adapted from Marieb EN, et al. 20133 and MDA4

Dystrophin is present in all muscles, including skeletal, cardiac and respiratory muscle.2,4,5 Dystrophin is a structural protein that provides mechanical stability5–7

Dystrophin protein structure and interactions

Adapted from Goemans N, et al. 20141
Dystrophin:
  • Links internal cytoskeleton to sarcoglycans/dystroglycansin the membrane and the extracellular matrix5,6
  • Provides mechanical stability and structure to muscle cell membrane during contraction5–7
  • Critical to structure/stability of all muscles, including respiratory and cardiac muscles5

The absence of dystrophin leads to muscle degeneration and fibrosis11,12

Once muscle is lost it cannot be replaced.2,10,12 The absence of dystrophin in Duchenne muscular dystrophy results in ongoing muscle damage, and replacement of muscle fibres by scar tissue and fat12

Adapted from Sweeney HL. 201413
With permission from H Lee Sweeney, PhD, Myology Institute, University of Florida, FL, USA.

By the age of 5, prominent muscle weakness becomes evident with a 50–60% drop in strength14

By age 6, only 60% of predicted muscle mass is retained, decreasing to just 20% at age 1615

Early intervention is critical to help delay disease progression and treat potentially life-threatening complications.2,8–10

Click here to find out how you can help.

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Carriers of Duchenne muscular dystrophy (DMD): symptoms & care

Approximately 10% of female carriers show some disease manifestations,1,2 which include:
muscle

Muscle weakness3-5

Cardiomyopathy3,4

Central nervous system manifestations4

Adapted from references 3-5

The 2018 Duchenne Care Considerations recommend performing cardiac assessment in all female carriers in early adulthood every 3–5 years.3 This should consist of an electrocardiogram and non-invasive imaging. Assessments should be more frequent in those who are symptomatic or imaging-positive.3

Diagnosis of DMD in children takes an average of 2 years from parental concern. Therefore, carrier women may have more children without realising that they carry a DMD mutation.6-8

Carriers may be at risk of Duchenne muscular dystrophy symptoms.3 Learn about the importance of carrier screening for Duchenne muscular dystrophy here.

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How common is Duchenne muscular dystrophy (DMD)?

DMD is an x-linked recessive disorder that primarily affects males.1,2 While a rare disease, it is the most prevalent of all neuromuscular disorders, affecting 1 out of every 3,600–6000 newborn males worldwide.2-4

If a female carries the mutation in the dystrophin gene on one of the two X-chromosomes, she may also be affected by DMD. Approximately 10% of female carriers show some disease manifestations, with cardiac involvement a frequent finding.2,5

Adapted from MDA6

Duchenne muscular dystrophy primarily occurs in males, but can affect females in some cases.1,2 Learn about carriers of Duchenne muscular dystrophy; symptoms and care here.

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The Duchenne muscular dystrophy (DMD) multidisciplinary care team

DMD care can be complex. It requires multiple interventions, including neuromuscular, respiratory, cardiac, orthopaedic, endocrine and rehabilitative. These will evolve over the course of the disease.1

As such, international care guidelines for DMD recommend a coordinated, multidisciplinary approach to care.1

By assembling a group of providers in a multidisciplinary team, the patient can benefit from:1

  • Integrated skills and knowledge from multiple disciplines
  • A coordinated and comprehensive treatment plan

Adapted from Birnkrant 2018 [Part 1] and Muscular Dystrophy UK1,2

Who are the key specialists in the DMD multidisciplinary care team?

muscle

Neuromuscular management1

KEY ROLE: to optimise the maintenance of muscle strength and function, lead the multidisciplinary clinic, and act as first point of contact to families

A neuromuscular specialist:

  • Leads, administers and coordinates the DMD multidisciplinary clinic
  • Characterises the patient’s disease trajectory and defines the treatment plan 
  • Provides patient and family support and education

Initiates and manages use of pharmaceutical interventions

Rehabilitation management1

KEY ROLE: to provide physical, occupational, and speech and language therapy

Professionals including physical therapists, occupational therapists, speech-language pathologists, orthotists and medical equipment providers:

  • Help prevent or manage muscle/joint contracture, deformity, falls and fractures 
  • Help prevent or manage pain
  • Promote exercise and activity
  • Provide orthoses, equipment and learning support

Cardiac management1

KEY ROLE: to evaluate cardiac function and manage cardiac complications

A cardiologist:

  • Monitors cardiac function and conducts cardiac assessments (in both DMD patients and female carriers)
  • Initiates and manages cardiac pharmacological therapies
  • Uses heart failure interventions with deterioration of function

Respiratory management1,6

KEY ROLE: to evaluate respiratory function and manage respiratory complications

Professionals including physicians and respiratory or physical therapists:

  • Monitor respiratory muscle function 
  • Manage lung volume recruitment, assisted coughing, nocturnally assisted ventilation and subsequent daytime ventilation
  • Manage immunisation schedules

Orthopaedic & surgical management1,6

KEY ROLE: to manage joint contractures and scoliosis

Professionals including physical therapists, occupational therapists, rehabilitation physicians, neurologists, orthopaedic physicians and social workers:

  • Provide surgical interventions to manage contractures and scoliosis
  • Provide physical therapy before and after surgery
spine

Bone health management1,6

KEY ROLE: to diagnose and treat osteoporosis

A bone heath expert:

  • Identifies early indications of bone fragility
  • Initiates and manages intravenous bisphosphonate therapy to treat osteoporosis

Psychosocial management1,3

KEY ROLE: to manage learning, emotional and behavioural disorders

Professionals including mental health clinicians, occupational therapists and physical therapists:

  • Assess mental health and educational needs
  • Provide neuropsychological evaluation/interventions for learning, emotional and behavioural problems

Specialist nursing2

KEY ROLE: to provide practical and emotional support for families affected by DMD

Specialist nurses:

  • Provide advice and information to patients and families about DMD
  • Support a patient’s physical and emotional wellbeing

Genetic counselling4,5

KEY ROLE: to manage genetic testing and explain what the results mean for families

A genetic counsellor:

  • Provides education about DMD
  • Coordinates and explains genetic testing
  • Provides emotional counselling
  • Discusses family planning options

Gastrointestinal and nutritional management1

KEY ROLE: to promote a healthy diet and weight, and manage any gastrointestinal problems

A dietitian nutritionist:

  • Monitors growth and weight to prevent undernutrition, malnutrition or obesity
  • Promotes a healthy, balanced diet
  • A gastroenterologist:Manages constipation, gastroesophageal reflux, gastrointestinal motility concerns and gastrostomy tube placement

Regional care services2,7

KEY ROLE: to provide practical and emotional support for families affected by DMD

Regional neuromuscular care advisors:

  • Help support patients in school and work environment
  • Assist in planning for major housing adaptations and equipment resources
  • Support the transition from child to adult medical care
  • Advise patients on disability benefit assessments
  • Educate other healthcare professionals about DMD

Endocrine management1

KEY ROLE: to manage endocrine complications of DMD and initiate hormone replacement therapy

An endocrinologist:

  • Manages hormone deficiencies and hormone replacement therapy in the case of impaired growth or delayed puberty onset
  • Educates families on the risks of adrenal crisis following glucocorticoid termination

Please note that the information in this table is intended to provide an overview only and is not exhaustive information. Please refer to the international care guidelines and any local guidelines for more information.

International care guidelines for Duchenne muscular dystrophy recommend a coordinated, multidisciplinary approach to care.1 Click here to learn more.

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Working together to improve the lives of patients and families

It is possible to help improve the quality of life and life expectancy of individuals with Duchenne muscular dystrophy.1,2 With the right care and access to adequate therapeutic strategies, healthcare teams have been able to:1,3
  • Help delay loss of ambulation
  • Reduce disease complications
  • Improve survival

For your patient, this can mean leading a fulfilling, independent life into adulthood.

These focused, two-page summaries provide you with a digestible overview of the 2018 International Duchenne Care Considerations.

Click on the summaries to view.

Diagnosis and management of Duchenne muscular dystrophy – Part 1
Diagnosis and management of Duchenne muscular dystrophy – Part 2
Diagnosis and management of Duchenne muscular dystrophy – Part 3

Studies have shown that early diagnosis and care can help slow Duchenne muscular dystrophy progression and minimise the risks and complications of the disease.1,2 Click here to find out how you can help drive a successful diagnostic journey.

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Genetic counselling offers many benefits for families living with Duchenne muscular dystrophy (DMD)

5 reasons to refer DMD families to a genetic counsellor:1-3

number 1

They provide education about DMD and its therapeutic options

number 2

They can coordinate diagnostic genetic testing

They can establish who is at risk of being a carrier and organise carrier genetic testing

They can discuss family planning options

They provide emotional counselling

International Care guidelines recommend that family members of an individual with Duchenne muscular dystrophy should receive genetic counselling to establish who is at risk of being a carrier.

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