Dystrophinopathies cause muscle weakness, predominantly in males, although 20% of females may also exhibit mild symptoms. Pathogenic variants in the DMD gene can cause one of three different conditions – Duchenne muscular dystrophy, Becker muscular dystrophy, or DMD-related dilated cardiomyopathy.
Duchenne muscular dystrophy (DMD) initiates in early childhood, impacting pelvic, thigh, shoulder, and hip muscles, leading to motor delays and an abnormal gait. Learning difficulties can arise, and wheelchair dependency typically occurs by age 13. Heart and respiratory muscles weaken, shortening life expectancy due to heart or respiratory failure. Becker muscular dystrophy (BMD) showcases varied, often milder symptoms that develop later than DMD, with a longer life expectancy. DMD-associated dilated cardiomyopathy (DCM) might occur independently of muscle weakness, progressing faster in males. Current treatments involve physical therapy, medication, and regular screenings, though gene therapy is available for some. Prognosis varies; DMD males usually face wheelchair dependence by 13 and may not survive past 30, while BMD males often live into their 40s or 50s. Females generally have a better outlook, although lifespan can be affected, especially with DCM. Rarely, males with DMD mutations might not display typical symptoms.
This group of conditions, as noted above, is caused by pathogenic (disease-causing) variants in the DMD gene on the X chromosome and exhibits X-linked recessive inheritance. This means that one pathogenic variant is enough to cause the disease in both males (who have one X chromosome and one Y chromosome) and females (who have two X chromosomes) may experience symptoms depending on how many copies of the X chromosome that has the pathogenic variant are turned on in the cells.
Females who are carriers of the disease are at an increased risk for dilated cardiomyopathy, and should also be seen regularly by a cardiologist.
Resources:
Muscular Dystrophy Association
Revised October 2023
