What are the causes of DMD? Expand DMD is caused by a defect in one of the genes in the body. Doctors call this a mutation. The largest gene in our bodies contains the instructions for making a protein called dystrophin. Dystrophin is found in all muscles in our bodies and plays an important role in protecting our muscles while they are working. All the genes in our bodies are packaged into ‘groups’ called chromosomes. These chromosomes are inherited from our father and mother. If you are a girl, you have two X chromosomes (one X from your mother and one X from your father). If you are a boy, you have one X chromosome (from your mother) and one Y chromosome (from your father). The dystrophin gene is only located on X chromosomes. As boys only have one X chromosome, DMD is much more common amongst boys. In two thirds of cases, the faulty dystrophin gene is passed from the mother to the child. These women are called ‘carriers’ because they carry the DMD gene although they do not have DMD themselves. In one third of cases, a spontaneous mutation happens at the beginning of the pregnancy. No one is to blame for either inherited genes or spontaneous mutations. There is nothing that anyone could have done before, during or after the pregnancy to prevent a child from developing DMD. Genes are very complicated and sometimes they go wrong.
What are the types of mutation in the DMD gene? Expand The dystrophin gene is made up of 79 active pieces of DNA (called ‘exons’). All 79 pieces are joined together in a sequence. This sequence communicates the genetic information needed to make the dystrophin protein. How does this cause DMD? Three different types of changes can prevent dystrophin being made, or cause an insufficient amount to be made: 1. Deletions of one or more whole exons – this is the most common type of mutation and is the cause of around 70% of cases of Duchenne. 2. Duplications (additions) of whole exons – this type of mutation is the cause of around 10% of cases of Duchenne. 3. Other small changes in parts of the genetic code, for example point mutations – this type of mutation is the cause of around 20% of cases of Duchenne. Currently, clinical trials are being conducted into ‘gene therapy’, to investigate how to create a working dystrophin gene. If you would like more information on how gene therapy can benefit patients with DMD, please click here.
What are the symptoms of DMD? Expand If you are worried that your child may have DMD, we urge you to speak to your GP as soon as possible. These are the symptoms and signs of DMD. If you notice that your child has these symptoms, please tell your GP.
What are the effects of DMD? Expand For children with DMD, muscle weakness starts in early childhood. It is first noticed between 2 and 5 years old. The ‘proximal’ muscles, like the hips and the shoulders, are the first to be affected. Often the earliest indication that a child may have DMD, is their difficulty in getting up from the floor, walking or running. Gradually, the child’s other muscles will begin to weaken as well. Without dystrophin, muscles become inflamed over time. As the muscles try to repair themselves, fatty or fibrous material builds up in the muscle and causes them to stop working altogether. This is called fibrosis and causes the muscles to become rigid and hard. Some children with DMD also have learning and behavioural difficulties This is because dystrophin is also found in the brain, although we are not yet sure of its purpose there. For more information about the different stages of DMD, please click here. Advances in research and knowledge of the disease are increasing life expectancy. Now, more and more young adults with DMD are leading full lives – going to university, having relationships and living independently. However, men and women with DMD do have a reduced life expectancy. Most adults with DMD will not live beyond their 40s.
What are the stages of DMD? Expand DMD is a progressive muscle-wasting disease, which means that symptoms worsen over time. Some parents prefer to read about the stage their child is currently at, while others want to know everything about the different future stages. We have divided up the stages of Duchenne muscular dystrophy here.
Who are female (or manifesting) carriers? Expand If a mother of a child with DMD has a mutation in her DNA that she passes to her child, she is called a “manifesting carrier.” These girls and women are called manifesting carriers because they produce reduced amounts of dystrophin. Some female carriers of a faulty dystrophin gene have very mild symptoms of DMD, including fatigue, mild muscle weakness and cramping. A female who is a carrier has an increased risk of developing cardiac and skeletal muscle weakness and dysfunction. Female carriers of DMD need to have their hearts checked every 3 to 5 years using ECG, cMRI or echo. Then, doctors will be tell if their hearts are normal or if have the same type of heart problems as people living with Duchenne. Some female carriers will need more frequent heart checks. If you know your carrier status, this will enable your doctor to work out the risk of heart problems for you and give you the appropriate advice and treatment. We recommend that you speak with your doctors and a genetic counsellor to explain this to you personally. Germline Mosaicism: A small number of women who do not test positive as carriers for Duchenne may still be able to pass a faulty DMD gene to their children. This situation is called germline mosaicism and is caused by a mutation in the DMD gene in the cells of some of the mother’s eggs. The mutation is not seen in the DMD gene in the rest of the mother’s cells - only her egg cells. If one of the affected eggs is fertilized, the baby will have DMD if a boy or be a female carrier if a girl. Around 15% of mothers of boys with Duchenne, who do not appear to be carriers, could pass a faulty DMD gene to their children in this way.
How is DMD caused in girls? Expand It is estimated that 1 in 50 million girls have Duchenne. It may be rare, but it does happen. Girls and women with DMD, Duchenne UK is here to support you. More boys than girls are affected by DMD because of the way the genes are passed down from parents to children. For more information, about genes and chromosomes, click on the ‘What are the causes of DMD?’ section above. A girl only develops DMD if both of her X chromosomes have faults in their dystrophin genes. This can only happen if one of the following extremely rare events takes place: - The girl inherits a faulty dystrophin gene on one of her X chromosomes from her mother and also develops a spontaneous mutation in her other X chromosome - The girl’s healthy dystrophin gene on one X chromosome becomes ‘switched off’ by a process called X-linked inactivation because she has inherited a faulty dystrophin gene on her other X chromosome - The girl’s father is a man with DMD and her mother is a woman who carried a defective DMD gene (‘a carrier’) - The girl develops spontaneous mutations in the DMD gene on both of her X chromosomes We are here to help everyone affected by DMD – girls and women, as well as boys and men.