HOW IS DUCHENNE DIAGNOSED?

Those observations can be made by:

• A parent or other family member
• A child’s paediatrician or GP
• A school nurse or teacher
• A health visitor
• A physiotherapist

Observations may include:

• Difficulty running, jumping and/or climbing stairs compared with other children of a similar age
• Struggling to get up from the floor or a chair (Gowers’ sign)
• Abnormal gait (way of walking), frequent falling, walking on tip-toes
• Enlarged calf muscles
• Speech delay

If the above signs and symptoms are observed, the first thing your GP will do will be to examine your child to check for muscle weakness. Your GP will also ask you about any delays you have noticed in your child’s early developmental milestones, such as sitting, walking and getting up from the floor.

If signs and symptoms of Duchenne are observed, your doctor may recommend a blood test. This involves taking a small sample of blood which will be sent to a lab for analysis to find out if there is a high level of a particular substance called creatine kinase (CK).

CK is an enzyme that is found in the heart, brain, skeletal muscle, and other tissues in the body. When muscle fibres are damaged, CK leaks out into the bloodstream. The muscle damage caused by Duchenne means that the level of CK in the blood can often be 10–100 times higher than normal.

If your child has a high CK level, your GP may refer him or her to a specialist children’s doctor (a paediatrician or a paediatric neurologist) or to a specialist centre.

Doctors will then work through a careful diagnostic process to identify the cause of the symptoms, and may recommend a variety of tests.

Genetic testing is used to confirm the majority of Duchenne diagnoses and can be done with a simple blood test.

Different genetic tests can also tell your doctor about the type of mutation that is causing Duchenne. There are different types of genetic tests and full gene sequencing may be needed to identify the specific type of mutation that is causing a child’s Duchenne. Knowing this is important because different mutations may be treated with different types of medication.

Another test that has been used to test for Duchenne is called a muscle biopsy. A muscle biopsy is not used to show the exact mutation that is causing Duchenne; instead, it is used to see if dystrophin can be found in the muscle that the biopsy was taken from. If genetic testing does not confirm a diagnosis of Duchenne, then a muscle biopsy may be performed.

If your child or relative DOES have Duchenne

Resources and treatment interventions are available to help manage symptoms and slow down the progression of the condition.

If your child or relative DOES NOT have Duchenne

Your doctor will do more investigations into what else could be causing symptoms.

Genetics is the branch of science that deals with how your physical and behavioural characteristics (including medical conditions) are determined by your DNA. Your genes are a set of instructions for the growth and development of every cell in your body – for example, the colour of your hair or eyes. Your genes can also directly cause a wide range of medical conditions such as Duchenne muscular dystrophy.

Duchenne is caused by a mutation (a defect or change) in the gene that makes dystrophin, a protein that keeps muscles working properly. As a result, the body cannot produce enough dystrophin, which makes muscle cells more sensitive to damage.

There are different types of mutations in the dystrophin gene that can change the functioning of the dystrophin protein and cause Duchenne. These are as shown below:

• Deletions
  This is when part of the dystrophin gene is missing. Most cases of Duchenne are caused by deletion mutations.
• Duplications
  This is when part of the dystrophin gene is repeated.
• Small mutations
  Various kinds of small mutations result in non or improperly functioning proteins. About half of small mutations are nonsense mutations. Nonsense mutations occur when a “stop signal” occurs before the functional protein has finished being made and so no working protein is available. Other small mutations include small deletions, small insertions and missense mutations.

These specific mutation types are identified through genetic testing.

Why is it important to know the mutation type?

There are disease management strategies being developed that depend on the mutation type. Therefore, knowing the mutation type can affect which of these strategies may be appropriate for an individual child.

A genetic counsellor can help interpret the results of a genetic test to determine which disease management strategies may be appropriate for that person.

The mutation in the gene that codes for dystrophin can be either:

• Passed on from one or both parents (inherited), or
• Caused by a new genetic change – this is called a ‘spontaneous mutation’.

Spontaneous mutations (also known as ‘de novo’ mutations) mean that sometimes Duchenne can occur without any family history of the disease. These new mutations can also be passed onto the next generation.

De novo mutations can arise in two ways:

1. The mutation occurs when the mother’s body makes the egg cell. If this particular egg cell is fertilised, the baby will carry a faulty dystrophin gene.
2. The mutation occurs at conception (when the mother becomes pregnant). In this case, the baby will carry a faulty dystrophin gene.

Normally, a female ‘carrier’ doesn’t show symptoms of Duchenne. This is because her healthy dystrophin gene will usually be able to produce enough of the dystrophin protein.

However, sometimes a girl is unable to produce enough dystrophin. This means that she will experience signs and symptoms, which can be treated in the same way as boys with Duchenne. Girls that show some symptoms of Duchenne are known as ‘manifesting carriers’.

In all carriers, regular strength checkups and close heart monitoring are important to make sure that any symptoms that may arise are properly treated. As a carrier ages, the risk of her developing heart issues increases. This is why it is so important for female relatives of a boy with Duchenne to get tested to find out whether or not they are carriers.

The chances of a carrier having a child with Duchenne are 1 in 4 (or 25%). This means that for every pregnancy, there is a 1 in 4 chance that the baby will have Duchenne. Once a Duchenne diagnosis has been made, it is important that you discuss your family planning options with your doctor and a genetic counsellor.

If you have a child or relative with Duchenne, you can ask your doctor about prenatal diagnosis during future pregnancies. There are different types of tests available and your GP or your genetic counsellor should be able to discuss these with you.

Other women in your close and extended family may also wish to find out if they are carriers. This will help them work out their chances of having a child with Duchenne.

Once you have the results, you can talk about what they mean for your family with a genetic counsellor.

Genetic counsellors are healthcare professionals who can help guide you through genetic tests and explain how the results might affect you or your family. They also provide you with emotional support and the resources to help you cope long-term.

4 REASONS TO SEE A GENETIC COUNSELLOR

They provide education about Duchenne and the genetic testing process

They can advise which female relatives should be tested to determine whether they are carriers

They can explain the results of genetic tests and discuss the best course of action

They will provide support throughout the genetic testing process

In addition to providing support and education, genetic counsellors can give advice on how to talk to other family members about the results of genetic tests. Specifically, they can help you:

• Understand which family members could be affected by Duchenne
• Understand the benefits and drawbacks of telling your family about Duchenne
• Decide when and how to tell your family about Duchenne
• Prepare what to say and decide what information you should share
• Anticipate and prepare for any questions they might ask
• Deal with any difficult emotions

The first physical symptoms of Duchenne may be hard to recognise, so it can be difficult to diagnose.

If you think your child or relative might have Duchenne, take these 3 steps to help your doctor determine whether it’s Duchenne or another medical condition.

WRITE DOWN YOUR FAMILY HISTORY

Understanding your family's history of muscle disease and other conditions can help your doctor reach a diagnosis.

KEEP A JOURNAL OF YOUR CHILD’S SYMPTOMS

Write down any symptoms you have noticed. Not sure what signs to look for? View the developmental milestones table here.

TAKE PHOTOS OR VIDEOS

Bring photos or videos to help your doctor gain a better understanding of the signs and symptoms you have observed.

Monitoring your child's development can be confusing.

The table below has been designed to help you understand the early signs that could indicate a developmental delay.

Remember that every child develops differently, so slight developmental delays do not automatically mean something is wrong. However, if you have concerns about your child’s development, it is important to speak to your GP as soon as possible.

Other early signs and symptoms can include:

• Gowers’ sign (pushing on floor and ‘climbing’ on legs to achieve a standing position)
• Waddling gait
• Enlarged calves
• Inability to keep up with peers