Muscular dystrophy

The most common form is Duchenne muscular dystrophy. This form is caused by mutations of the gene for the dystrophin protein. The dystrophin is the second largest gene in mammals. The dystrophin gene is located on the X chromosome, thus making it a 'sex-linked' disorder. Accordingly, muscular dystrophies are much more common in males, as females have two copies of the X chromosome while males have only one.

Role of heredity

Duchenne muscular dystrophy is caused by an X-linked gene. This means that only boys are affected but that their mothers may be carriers. In almost half of all affected boys, the faulty gene has arisen by mutation in the boy himself and no other family member carries it. However, this may be difficult to prove and can be decided only after careful and expert assessment of the family.

In the remaining cases (somewhat over half of all cases), the mother carries the gene but is usually not herself affected by it. Such women are known as ‘carriers’. Each subsequent son of a carrier has a 50:50 chance of being affected and each daughter has a 50:50 chance of being a carrier herself. A small number of female carriers of the gene have a mild degree of muscle weakness themselves and are then known as ‘manifesting carriers’.

One of the most important things that needs to be done soon after the diagnosis of a boy with Duchenne muscular dystrophy is to seek genetic advice and appropriate tests for those family members who are at risk of being carriers.

Common forms

Duchenne MD is the most common form of muscular dystrophy affecting children, and myotonic muscular dystrophy is the most common form affecting adults. Muscular dystrophy can affect people of all ages. Although some forms first become apparent in infancy or childhood, others may not appear until middle age or later.

Incidence

About a 100 boys with Duchenne muscular dystrophy are born in the UK each year. There are about 1,500 known boys with the disorder living in the UK at any one time. For the general population the risk of having an affected child is about one in every 3,500 male births.

The most frequent symptoms are muscle weakness (frequent falls, walking problems, drooping eyelid) and skeletal and muscle deformities. Neurologic examination often reveals loss of muscle tissue (wasting), muscle contracture, pseudohypertrophy, and weakness. Diagnosis is usually established by muscle biopsy, elevated serum creatine kinase levels and electromyography, which is consistent with myogenic involvement. Some types of muscular dystrophy may present with additional cardiac disease, intellectual deterioration and infertility.

renatal diagnosis

Female carriers of muscular dystrophy who are considering having children should be aware that prenatal diagnosis is available. Tests can be carried out during pregnancy, to try to find out if the fetus (unborn child) is affected.

A couple may want to consider whether or not to continue the pregnancy if the fetus is affected. Alternatively, they may wish to know if the fetus is affected so that they can carry on with the pregnancy armed with knowledge that will help them to prepare and plan for the future.

Different types of prenatal tests can be carried out after about 10 weeks of pregnancy. Chorionic villus sampling (CVS) can be done at 10-12 weeks, and amniocentesis at about 14-16 weeks, while placental biopsy and fetal blood sampling can be done at about 18 weeks.

Treatment

There is no known cure for muscular dystrophy. Inactivity (such as bed-rest and even sitting for long periods) can worsen the disease. Physical therapy and orthopedic instruments (e.g., wheelchairs, standing frames) may be helpful.

There is no specific treatment for any of the forms of muscular dystrophy. Physical therapy to prevent contractures (a condition in which shortened muscles around joints cause abnormal and sometimes painful positioning of the joints), orthoses (orthopedic appliances used for support) and corrective orthopedic surgery may be needed to improve the quality of life in some cases. The cardiac problems that occur with Emery-Dreifuss muscular dystrophy and myotonic muscular dystrophy may require a pacemaker. The myotonia (delayed relaxation of a muscle after a strong contraction) occurring in myotonic muscular dystrophy may be treated with medications such as quinine, phenytoin or mexiletine.

Prognosis

The prognosis of muscular dystrophy varies according to the type of muscular dystrophy and the progression of the disorder. Some cases may be mild and very slowly progressive, with normal lifespan, while other cases may have more marked progression of muscle weakness, functional disability and loss of ambulation. Scoliosis is commonly seen in Duchenne muscular dystrophy and in spinal muscular atrophy (types 2 and 3). It is also seen in some types of congenital muscular dystrophy and in other rarer neuromuscular conditions. If a child or adult has a neuromuscular condition in which scoliosis can be a feature they should attend a specialist clinic where their spine can be checked on a regular basis. If a scoliosis starts to develop spinal surgery may be offered.

Life expectancy may depend on the degree of progression and late respiratory deficit. In Duchenne muscular dystrophy, death usually occurs in the late teens to early twenties.

The use of mechanical ventilation and heart medications have been shown to prolong life in DMD