Duchenne Muscular Dystrophy - Specialists and Information

Duchenne muscular dystrophy is caused by a mutation in the dystrophin gene. It is inherited in an X-linked recessive pattern, meaning that the disease affects almost exclusively boys.

Von Kuebi = Armin Kübelbeck - own work. People sketches taken from Image:Autorecessive.svg created by en:User:Cburnett. Idiograms taken from Chromosome Y.svg and Chromosome X.svg, both created by en:User:Mysid. Created with Inkscape. PNG file derived from SVG master file, CC BY-SA 3.0, Link

In 2/3 of cases, the mother passes the defective gene on to her son. Since the mother has two X chromosomes, the condition does not manifest in her (she is a carrier). And if it does, it manifests only as mild heart failure. This often goes unrecognized until her son is diagnosed.

In 1/3 of cases, the condition is not inherited but arises from a new mutation (de novo mutation).

The genetic defect prevents the body from producing dystrophin, a protein essential for the muscle membrane. The muscle cell membrane becomes unstable, triggering progressive muscle wasting.

The first symptom of Duchenne muscular dystrophy is a delay in learning to walk unaided. Some affected boys, however, show no noticeable motor problems during the first 1 to 2 years of life.

Delayed speech development is disproportionately common in these boys, even though their intellectual development is normal.

Motor problems begin around preschool age. The boys fall more often than other children. Their endurance for longer distances also decreases, and they are less coordinated than their peers.

The boys’ strikingly strong calves appear to contradict these motor problems. The strong calves are not due to greater muscle mass, but rather to a connective-tissue-related remodeling of the muscles accompanied by fat deposition. Medical professionals also refer to this process as pseudohypertrophy. 

The boys have increasing difficulty standing up from the floor. If they have nothing to hold onto, they use their thighs to support themselves as they stand up (positive “Gowers’ sign”).

The boys develop:

• a waddling gait (positive Trendelenburg sign)
• a pronounced swayback due to weakness of the abdominal and back muscles, and 
• increasing muscle contractures

This involves reduced joint mobility due to shortened tendons. Between the ages of 10 and 12, they are no longer able to walk more than a few steps. They are dependent on a wheelchair.

As the condition progresses, increasing weakness of the arm muscles also becomes apparent. This leads to muscle weakness and a curvature of the spine (scoliosis). 

Other organ systems affected in later stages include:

• the heart (possible impairment of pumping function) and 
• the respiratory muscles

A presumptive diagnosis can be made based on typical clinical signs, such as:

• male gender
• muscle weakness
• Calf hypertrophy
• Waddling gait

As a first step, doctors measure the level of the muscle enzyme creatine kinase (CK) in the blood. In Duchenne muscular dystrophy, this level is significantly elevated. 

In the past, the next step involved an EMG examination and a muscle biopsy. Today, a diagnosis can be made using genetic testing.

To date, there is no cure for Duchenne muscular dystrophy. However, numerous studies are underway to test various treatment approaches in animal models and clinical trials.

In the meantime, the first drug has been approved (ataluren). However, it is effective only for a specific mutation (genetic change). 

This is a nonsense mutation, which is present in only about 13 percent of all Duchenne patients.

Even without a curative treatment, there are several important therapeutic approaches. These are primarily aimed at maintaining muscle strength for as long as possible and preventing joint contractures.

In addition to regular physical therapy, boys are often treated with corticosteroids. These extend the ability to walk by approximately 2 years.

Other important measures include:

• Weight
• Heart and lung function
• Provision of assistive devices
• School-related issues and 
• Social services

An international group of experts has developed a corresponding framework for treatment standards (www.treat-nmd.de).

As treatment progresses, various other medical specialties are involved alongside the pediatric neurologist, such as:

• Cardiologists
• Pulmonologists
• Orthopedists
• Physical therapists
• Occupational therapists and 
• Speech-language pathologists

Thanks to new treatment options, the average life expectancy of patients has increased significantly over the past 20 years.

If cardiac findings are stable, life expectancy can extend into the fourth decade of life. Unfortunately, however, those affected must cope with significant limitations in their quality of life.