Duchenne muscular dystrophy (DMD) is a severe progressive inherited disease characterized by muscle wasting and ultimately culminating in death. It’s a common enough neuromuscular disorder that pediatricians and family practice physicians are likely to see at least a couple of patients with DMD over the course of their career,” John Brandsema, MD, Neuromuscular Section Head, Division of Neurology, Children’s Hospital of Philadelphia in Pennsylvania, said in an interview. Healthcare providers should therefore be familiar with the disorder so as to provide timely diagnosis and early intervention as well as practical and emotional support to the patient and family/caregivers as they traverse the challenging and often heartbreaking journey with this condition.
Pathophysiology and Disease Trajectory
DMD is caused by pathogenic variants in the X-linked DMD gene, leading to reduction in dystrophin, a protein that serves as a cytoskeletal integrator, stabilizing the plasma membrane of striated muscle cells. Dystrophin is critical for muscle membrane stability.2 In particular, mutations in the gene that encodes for dystrophin lead to dysfunction in Dp427m, which is the muscle isoform of dystrophin.3,4
DMD is one of several types of muscular dystrophies. All are progressive disorders. Over time, healthy muscle fibers disappear and are replaced by fibrotic tissue and fat, making the muscles “less able to generate force for everyday activity.”2 Ultimately, the skeletal muscle dysfunction affects not only the patient’s day-to-day mobility but other systems as well. Most patients with DMD eventually die of cardiac and/or respiratory failure between the ages of 20 and 40 years, with a median life expectancy of 22 years — although children born after 1990 have a somewhat higher median life expectancy (28 years), because of the improving standard of care.3,5
Typically, DMD first presents with developmental delays and weakness in skeletal leg muscles. As the disease goes through stages of progression, it starts involving upper extremities and other systems. (Table 1)
Genetic Causes of DMD
The DMD gene, located on the X chromosome, encodes for the production of dystrophin. Variants of this gene result in the lack of dystrophin protein, leading in turn to muscle fiber degeneration and the progressive symptoms of DMD. Because of the gene’s location on the X chromosome, males (who don’t have a second copy of the X chromosome) cannot compensate for the mutated gene, which is why the disease affects male children. Females with this mutation are carriers and typically do not develop the same severity of symptoms, although they might have milder muscle cramps, weakness, and cardiac issues.3
A female carrier with DMD (or any other X-linked disorder) has a 25% chance to have a carrier daughter, a 25% change of having a noncarrier daughter, a 25% chance of having an affected son, and a 25% chance of having a nonaffected son. A male with the disorder will pass the mutated gene on to his daughters who then become carriers. He cannot pass the disorder on to his sons because males inherit only the Y chromosome from their fathers.3