Duchenne muscular dystrophy DMD is an inherited disorder that causes progressive muscle weakness. It primarily affects muscles close to the center of the body, causing problems with walking and breathing.

The MEDLINE and EMBASE databases were searched by two authors individually for original observational research articles reporting DMD incidence, prevalence or birth prevalence, written in English. The STROBE checklist was used to assess study quality.

Symptoms

Duchenne muscular dystrophy (DMD) is a genetic disease that causes muscle weakness and wasting. It affects about one in 5,000 boys and is the most common type of muscular dystrophy. It is caused by changes in the gene that helps make dystrophin, a protein found in muscle cells. Children with DMD start losing their muscle strength in early childhood and usually need a wheelchair by the time they are teenagers. Muscles used for movement are affected first, including the muscles that help to stand and walk. Eventually, the weakening of these muscles leads to a waddling gait and scoliosis. DMD can also cause problems with the heart, including enlarged (dilated) cardiomyopathy.

DMD is inherited in families, usually through an X-linked recessive mutation. Some females who have a problem with the dystrophin gene do not develop symptoms, but they are carriers and can pass it on to their children. Affected males often have a family history of the disease, but DMD can occur with no known family history.

Diagnosis

Generally, boys with DMD have an elevated creatinine kinase and are found to have a mutation in the dystrophin gene. They are usually diagnosed after a careful review of the history and examination, muscle biopsy and molecular genetic testing.

Muscle weakness is the main symptom. It usually starts in the proximal muscles (those closest to the core of the body). Symptoms include difficulty jumping, running and climbing stairs, enlargement of the calf muscles, a waddling gait and lumbar lordosis (an inward curve of the spine). In later stages, the heart and breathing muscles are affected.

Children with DMD need a multidisciplinary team of healthcare providers to monitor them and to treat any complications that may arise. This includes neurologist, physiotherapist, speech and language therapist and psychologist. It’s important for the family to find support from other families living with DMD and to attend a local support group. They also need to keep in regular contact with their local MDA Care Center.

Treatment

While there is no cure for DMD, advances in cardiopulmonary care have improved life expectancy and health-related quality of life. Many boys with DMD live into their early 30s, attend college and careers, marry, and have children.

Genetic testing is available for the X-linked disorder that causes DMD. Talk to your family doctor or neurologist about getting genetic testing for DMD.

Treatment options focus on reducing symptoms and maintaining function and independence for as long as possible. These include glucocorticoids (prednisolone, deflazacort, and now the newly approved vamorolone) that slow the decline in muscle strength; pulmonary and heart monitoring; and noninvasive positive pressure ventilation (NPPV) if breathing becomes difficult.

Exon skipping drugs—also known as peptide modulators—resolve a subset of mutations in the dystrophin gene by partially correcting the reading frame for the protein dystrophin, and are showing promising early results in human clinical trials. The first drug to be studied is eteplirsen (PTC124), which skips exon 53, and a newer drug called golodirsen (Vyondys 53, Sarepta Pharmaceuticals) has expanded the eligible DMD population for reading frame correction to 8% of all affected boys.

Preventative measures

Preventative measures are aimed at optimizing muscle function, preventing contractures and scoliosis, and reducing complications related to the impaired bone metabolism, such as compression fractures. Plasma CK levels should be measured from birth as elevated levels indicate ongoing muscle damage and are an indication of the severity of the disease.

A multidisciplinary team including physiotherapists and orthotists is essential to improve functional ability. It is important to monitor the development of a scoliosis and of a thoracic deformity, assess ambulation and breathing and consider early respiratory intervention with a tracheostomy or a mechanical ventilator.

A muscle biopsy is usually not necessary to confirm the diagnosis of DMD as MLPA and array CGH can detect the majority of deletions and duplications and identify their consequences in dystrophin protein function. mRNA can be isolated from the muscle biopsy and the sequence can be analysed for frameshift mutations (changing codons in the protein’s coding region) or nonsense mutations that cause premature truncation of protein translation, both of which can be diagnosed with 90% accuracy using specific databases124.