Duchenne muscular dystrophy (DMD) is an X-linked disease that affects male children. It causes progressive muscle weakness and impaired breathing. It is a devastating and terminal illness that requires multidisciplinary care and a life-long commitment to standards of care. This systematic review provides a broad overview of the global epidemiology of DMD, with pooled prevalence and birth prevalence estimates of 7.1 (95% CI 5.0-10.1) and 19.8 (95% CI 16.6-23.6) per 100,000 males. A high degree of between-study heterogeneity was observed.

Symptoms

Duchenne muscular dystrophy (DMD) causes muscle weakness, usually beginning in the legs. Weakness gradually spreads to the arms, shoulders, and neck. By age 12, most affected children use wheelchairs.

Weakness can also affect the muscles that operate the lungs. This leads to weakened coughing, which increases the risk of serious respiratory infections. Weakened back muscles may cause a curvature of the spine called scoliosis.

Girls are less likely to develop X-linked disorders because they have two copies of the healthy gene that compensates for the mutation. However, girls who have a father with DMD have a 50 per cent chance of being carriers of the mutation and developing symptoms later in life. Genetic blood tests can identify the presence of the mutation that causes absence of dystrophin.

Diagnosis

DMD is usually diagnosed in children between the ages of 2 and 3. It mainly affects boys, but can also occur in girls.

Your child’s doctor will take a blood sample and check it for creatine kinase (CK) levels. These can rise if muscles are weak. They may also do a muscle biopsy. This involves inserting a needle into a muscle to remove a tiny piece. They will then examine the tissue under a microscope to look for a change in the gene that causes DMD.

DMD can cause heart and lung problems, so your child will need an electrocardiogram and echocardiogram to check for these. DMD can also affect the muscles of the spine, so your child might need surgery to correct scoliosis.

Treatment

Treatment is focused on slowing muscle deterioration and improving quality of life. This includes drugs to improve movement and support skeletal muscles (such as prednisone or deflazacort), breathing medications, nutritional support and physical therapy (including passive stretching to prevent contractures in the joints).

Currently there are gene replacement therapies being developed that target faulty protein production and reduce inflammatory mechanisms that cause damage to muscle cells. These are showing promise in prolonging life expectancy by delaying heart and respiratory failure.

Most children with DMD can attend a mainstream school, with adjustments made for their physical and learning needs. They will be able to participate in extracurricular activities such as music or drama. They can also receive mental health support and advice to help cope with the diagnosis.

Genetics

Genetic research has improved our understanding of how DMD and BMD develop. Thousands of mutations have been found in patients with DMD. These mutations cluster in regions known as hotspots where the DMD gene is highly prone to damage2,17.

These mutations are caused by a problem with the gene that makes dystrophin. DMD is an X-linked disorder because males have only one copy of the gene located on the X chromosome.

Female carriers do not experience DMD symptoms but can pass the faulty dystrophin gene to their children. Females should be offered screening for DMD from mid to late adolescence. They should also be educated on the risk of developing cardiomyopathy and should have regular echocardiograms. In some cases, these girls may be recommended to have genetic testing through chorionic villus sampling or pre-implantation genetic diagnosis in order to avoid passing the DMD mutation to their offspring.

Life expectancy

Although there is no cure for DMD, ongoing clinical trials and new medications are adding years to life expectancy. But the condition does progress over time, and complications like heart or lung problems are often fatal.

Because DMD is a rare disease, there are few studies of patient survival in this patient population. This study aimed to improve upon previous work by providing appropriate estimates of survival probabilities/mortality rates at different ages.

This was achieved by conducting a systematic review of published literature in which Kaplan-Meier (KM) curves with age as a timescale were present and digitized. This enabled the reconstruction of individual patient data (IPD) and the calculation of pooled estimates. These estimates will enable future natural history and economic modeling of DMD.