Introduction to Duchenne Muscular Dystrophy
Duchenne muscular dystrophy (DMD) is a muscle-wasting condition (neuromuscular disorder) caused by a mutation in the dystrophin gene leading to an absence of a type of protein called dystrophin in the muscle fibres. It usually affects only boys.
It is exceptionally rare for girls to have Duchenne, although not unheard of. But girls and mums of DMD boys / young men, in particular, can be “manifesting carriers” i.e., they can have calf hypertrophy, which is often asymmetrical, some weakness, difficulty getting off the floor and managing stairs, muscle aches and cramps.
In severe cases girls, like boys, can lose ambulation. They may be asymptomatic or present more like a Becker muscular dystrophy (milder phenotype) and present with muscle cramps and mild weakness or motor difficulties. It is important to assess them using similar techniques as with Duchenne muscular dystrophy, but you may need to include some higher functional abilities such as rising through half-kneeling or ability to squat. (These are items which can be found in the NSAD – which is primarily for assessing children and adults with a limb girdle muscular dystrophy).
Take note if a mother is a manifesting carrier and ask her about any difficulties that she may have. This can affect what she is able to do for her child, and more emphasis may have to be placed on management at nursery or school.
Key message – it is important for therapists to know that mothers will need monitoring for potential cardiac issues. They do present in our clinics and may show signs of muscle weakness later in life. It can be useful to perform manual muscle testing and assess function in this group.
About 100 boys are born in the UK each year with Duchenne muscular dystrophy, and there are about 2,500 boys and young men known to be living with the condition in the UK at any one time.
For the general population, the risk of having a child with Duchenne muscular dystrophy is about one in every 3,500-5,000 male births.
Duchenne muscular dystrophy is a serious condition that causes progressive muscle weakness. Owing to the lack of the dystrophin protein, muscle fibres break down and are replaced by fibrous and or fatty tissue, causing the muscle to weaken gradually.
A milder phenotype exists called Becker muscular dystrophy where some dystrophin is expressed in the muscle, but it is not fully expressed. It presents as a milder disease but is still progressive. A higher function may be achieved but muscle weakness does occur in the same pattern as with Duchenne muscular dystrophy (proximal to distal progression) and muscle cramps in the calf muscles and thighs are quite common.
Duchenne muscular dystrophy is a genetic condition – it is caused by a mutation in the genetic code (DNA).
In Duchenne muscular dystrophy, the mutation occurs in a gene called dystrophin, which is located on the X chromosome or sex-chromosome (girls have two X chromosomes and boys have only one). In just over half of cases, the condition is inherited from the mother who is a ‘carrier’, but it can also be caused by a new mutation in the child’s genes.
If a woman carries the mutation, then she is known as a ‘carrier’. Usually, female carriers are not affected because they have a second X chromosome, from which the dystrophin protein can be produced. A small number of female carriers have a degree of muscle weakness themselves, and they are known as ‘manifesting carriers’.
Each son of a carrier has a 50:50 chance of being affected, and each daughter has a 50:50 chance of being a carrier. Genetic advice (counselling) and testing for other family members at risk of being carriers, should be provided as soon as possible following the diagnosis of a boy with Duchenne muscular dystrophy.
Most boys with Duchenne muscular dystrophy are not diagnosed until they start displaying symptoms, unless there is someone else in the family with the condition.
The first signs of Duchenne muscular dystrophy usually appear between the ages of one and three years and usually consist of problems with muscle function – see Diagnosis and Management of DMD Video in the resources section below.
Boys might start walking later than their peers, can fall more often or show difficulty running, jumping or getting up from the floor. They might have enlarged calf muscles. Some boys with Duchenne muscular dystrophy have delayed speech development and this can be the first sign of the condition.
The first indication, which may be tested by local or specialist services, is an extremely elevated level of a protein called creatine kinase (CK) which is an indicator of muscle damage and is often a value in the 1000’s as opposed to normal CK values (generally up to 250 U/L (units per litre)). If a blood test is done, high levels of a protein called creatine kinase (CK) are seen, which may be indicative of Duchenne muscular dystrophy and would require further investigation by a specialist service.
Duchenne muscular dystrophy must be confirmed by genetic testing usually on a blood sample. Different types of genetic tests can provide specific and more detailed information about the DNA mutation.
Genetic confirmation is crucial. It enables families to make decisions about prenatal diagnosis in future pregnancies and for genetic testing to be available to other family members at risk of carrying the mutation in the dystrophin gene. Moreover, the genetic diagnosis will assist in determining if the boy qualifies for a number of clinical trials, which are currently running or are planned. Muscle biopsies are no longer required for diagnosis.