dystrophinopathy (including Duchenne/Becker muscular dystrophy)

What are Dystrophinopathies (including Duchenne/Becker Muscular Dystrophy)?

Dystrophinopathies are a group of conditions that generally cause muscle weakness. They are caused by harmful genetic changes (variants) in the DMD gene. There are two main forms of dystrophinopathies related to the DMD gene: Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). DMD and BMD are inherited in an X-linked manner. This means the condition is typically more severe in individuals assigned male at birth (XY). However, individuals assigned female at birth (XX) may also have symptoms of the condition.

Common presentations of DMD and BMD are described below. It is not always possible to predict, based on a genetic testing result, which of the presentations could occur in a child who has a variant in the DMD gene. Additionally, there have been rare reports individuals with a variant in the DMD gene who do not have the characteristic symptoms described below.

Duchenne Muscular Dystrophy

The primary symptoms of DMD are weakness and breakdown of muscles, which get worse over time. Symptoms typically begin in early childhood, with weakness in the muscles of the hips, pelvic region, thighs, and shoulders. This results in an abnormal way of walking (gait) and delays in sitting up, standing, and walking (general motor skills). A small percentage of affected individuals also develop learning difficulties early in life, though the level of intellectual disability is variable. Because DMD gets worse over time, most affected individuals will need a wheelchair by 13 years of age. By the mid-teenage years, the heart muscles will weaken (this is known as dilated cardiomyopathy or DCM), as will the respiratory muscles. This weakening causes a shortened life expectancy.

Becker Muscular Dystrophy

The primary symptoms of BMD are also muscle weakness and DCM. However, symptoms are much more variable in presentation, may be milder, and tend to develop later than DMD. Individuals with BMD also generally have a longer life expectancy than those with DMD.

DMD-Associated Dilated Cardiomyopathy

DMD-associated dilated cardiomyopathy (DMD-associated DCM) may occur without any muscle weakness. DCM can lead to heart failure, with symptoms usually starting between 20 and 40 years of age.

Additional considerations for carriers

XX individuals (who are typically assigned female at birth) are carriers of DMD and BMD. While many carriers do not have symptoms, some may develop symptoms, including muscle weakness and cramping. Many carriers will have heart problems, including DCM. Symptoms reported in carriers are generally much milder and start at a later age than those in XY individuals.

How common are Dystrophinopathies (including Duchenne/Becker Muscular Dystrophy)?

Together, the incidence of DMD and BMD is an estimated 1 in 3,000. Approximately 1/3 of individuals affected by DMD or BMD do not inherit a variant from a parent (a de novo change).

How are Dystrophinopathies (including Duchenne/Becker Muscular Dystrophy) treated?

There is no cure for DMD-related dystrophinopathy; a combination of physical therapy, medication, and regular cardiac and respiratory screenings is the current standard practice for treating the condition. Carriers are at an increased risk for DCM and should also regularly see a cardiologist. Affected individuals with specific variants in the DMD gene may be eligible for FDA-approved dystrophin restoration therapies (such as Eteplirsen, Golodirsen, Viltolarsen, or Casimersen). These therapies are not a cure but may be able to reduce the severity of muscle weakness in DMD cases. However, more research is needed to confirm the clinical benefits.

What is the prognosis for individuals with Dystrophinopathies (including Duchenne/Becker Muscular Dystrophy)?

The prognosis for DMD is variable, but most individuals will be wheelchair-dependent by age 13 and die before 30 years of age due to heart or respiratory failure. Individuals with BMD have a longer life expectancy, typically reaching their forties or fifties. In rare cases, individuals with a variant in the DMD gene may not experience the characteristic symptoms of dystrophinopathies.