What is Duchenne?

About Duchenne

Duchenne is a genetic disease that causes muscle weakness and wasting. It’s a progressive, life limiting condition.

Duchenne is caused by a mutation in the dystrophin gene and it is typically diagnosed in childhood between the ages of three and six. You can find out more the genetic causes of Duchenne and how it is inherited here.

Duchenne is a multi-system disease which causes all the muscles in the body to gradually weaken, including the heart, and breathing muscles.

Duchenne can affect any ethnicity. It generally affects boys and young men, but can in rare cases also affect girls. It affects around 1 in every 5,000 live male births each year but only around 1 in 50 million girls. 

It is estimated that there are 2,055 people in the UK living with Duchenne. 

There is currently no cure for Duchenne, but there is hope. We are at the forefront of advancing treatments and care for everyone affected by the disease.

Current treatment and supporting therapies for Duchenne can help to ease the symptoms of the disease. Duchenne UK is funding research into new treatments that could have greater impact and more acceptable side effects.

Early signs and symptoms

In early stages, Duchenne affects the limb muscles, with the legs more noticeably affected before the arms. Children with Duchenne are often late walkers. Muscle weakness is most noticeable when children run or get up from the floor.

Early signs can include delays in hitting early developmental milestones such as sitting, crawling and walking and/or speech and language delay. Speech delay and the inability to keep up with peers may be the first signs but this may not be the case for all children with Duchenne.  

Early symptoms can also include:

• Delay in the ability to sit and stand independently
• Large calf muscles (known as pseudohypertrophy)
• Trouble running and jumping
• Unusual gait when walking
• Using the Gower’s Manouevre to get off the floor (using their hands and arms to “walk” up their own body from a squatting position).
• If you are concerned that your child has early signs or symptoms of Duchenne, visit your doctor.

What causes Duchenne?

Duchenne is caused by a change or fault, known as a mutation, on the dystrophin gene. Dystrophin is a protein that protects muscles; without it, muscles are easily damaged and not able to repair themselves, meaning their strength and function is weakened over time. 

Becker muscular dystrophy which can be slower progressing than Duchenne, occurs when some dystrophin is produced, but not in the normal form or amount.

There are three errors, called mutations that can prevent any or enough dystrophin being made in the body leading to someone having Duchenne:

• Exon deletion – this means that one or more exons in the dystrophin gene is missing. This is the cause of around 70% of cases
• Exon duplication – around 10% of cases are caused by one or more exons having extra copies in the dystrophin gene.
• Other small changes, such as tiny deletions of genetic code or nonsense mutations. These cause around 20% of cases.

The genetic defect that causes Duchenne can either be:

• Inherited (passed down through the family

• Caused by a new change in the Duchenne gene that occurs in the child. This new genetic change is known as a ‘spontaneous mutation’ and is the cause in more than one third of cases of Duchenne. The genetic change occurs very early in development of the egg that has been fertilised which means that the change is found in all of the cells of the body.

When a child is diagnosed with Duchenne, genetic counselling and assessment should check if the mother is a carrier. If this is confirmed, testing can be offered to other female family members (daughters, maternal aunts and grandmothers). 

Duchenne carriers should have regular heart checks about every 3-5 years, from the point of their diagnosis onwards. If heart problems are identified, combination treatment (typically ACE inhibitor and MRA) can be started to protect the heart. After starting these treatments, Duchenne carriers should have yearly heart checks. You can read more about recommended cardiac care for female carriers here.

Females who are identified as carriers and are planning pregnancy should have pre-conception genetic counselling, so that they understand the risks of passing on the Duchenne gene to their children and their fertility options.

How is Duchenne inherited?  

In around two thirds of cases of Duchenne, the genetic change is passed down through the family from the mother.

Each person inherits a set of genes from their father and another set from their mother. The genes have been copied from the parents' cells into the child's cells.

You may hear Duchenne referred to as an ‘X-linked recessive genetic condition’. This is because the dystrophin gene is found on the X-chromosome. This means that Duchenne primarily affects males, while females are typically carriers meaning that they carry the faulty gene but are unaffected by the condition. This is because females have two X chromosomes, compared to males, who have one X chromosome and one Y chromosome. Males have Duchenne if they inherit the X chromosome with a fault in the dystrophin gene from their mother. 

Overall with each pregnancy in a female carrier of Duchenne, there is a 1 in 4 (25%) chance that a male with Duchenne will be born – as there is a 50% chance the child will be male and 50% chance that male will inherit the dystrophin gene. 

There is also a 1 in 4 chance that a female who carries the Duchenne gene will be born.

On the other hand, if a male with Duchenne was to have children with a non-carrier female, none of their sons would have Duchenne, although all of their daughters would be carriers. This is because females inherit one X chromosome from their mother and one from their father, and in this case the father’s X chromosome has the faulty dystrophin gene which would be passed to the daughter, making them a carrier.

Germline Mosaicism

A small number of women who do not test positive as carriers for Duchenne may still be able to pass a faulty Duchenne gene to their children. This situation is called germline mosaicism and is caused by a mutation in the Duchenne gene in the cells of some of the mother’s eggs. 

The mutation is not seen in the Duchenne gene in the rest of the mother’s cells. If one of the affected eggs is fertilized, the resulting child will have Duchenne if a boy or be a female carrier if a girl. It is estimated that around 15% of mothers of boys with Duchenne, who do not appear to be carriers, could pass a faulty Duchenne gene to their children in this way.

Girls and Duchenne

A girl can have Duchenne if both of her X chromosomes have faults in the Duchenne gene.

This is extremely unlikely although it could happen in a number of different ways. A girl could inherit a faulty Duchenne gene on one of her X chromosomes from her mother and also develop a spontaneous mutation in her other X chromosome. She could also develop spontaneous mutations in the Duchenne gene on both of her X chromosomes.

It is also thought that the healthy Duchenne gene on one X chromosome can become ‘switched off’ by a process called X-linked inactivation in some girls that have inherited a faulty Duchenne gene on their other X chromosome.

Alternatively, if a man with Duchenne and a woman who carried a defective Duchenne gene ‘a carrier’ had a child, it is possible that a daughter would have Duchenne.

Female carriers of a faulty Duchenne gene can also have very mild symptoms of Duchenne that progress slowly. These women are called ‘manifesting carriers’ because they produce reduced amounts of dystrophin. This is not the same as having Duchenne but they may have symptoms such as fatigue and mild muscle weakness and cramping, and they will have an increased risk of heart problems.