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16 | InTouch SPRING 2025 Some female carriers of Duchenne or Becker Muscular Dystrophy may also experience symptoms themselves; these are known as manifesting carriers. Manifesting carriers of Duchenne or Becker Muscular Dystrophy YOUR CONDITION IN REVIEW A manifesting carrier is a female who carries a genetic mutation for Duchenne or Becker Muscular Dystrophy (DMD or BMD) and displays symptoms of the muscle disorder. Manifesting carriers represent approximately 10–20% of all female carriers of DMD or BMD mutations. Symptom onset typically occurs between ages 16 and 48, and severity can range from mild generalised weakness to loss of ambulation. Features Manifesting carriers display a spectrum of symptoms, from mild muscle aches to significant muscle weakness and, in rare cases, loss of ambulation. Key features include: • Muscle symptoms: Myalgia (muscle pain), cramps, progressive weakness (often affecting the upper arms and thighs), clumsiness, and increased risk of falls. Weakness may be asymmetric. • Pseudohypertrophy: Enlarged calf muscles, which appear strong but are weak. • Exercise intolerance: Fatigue and difficulty with activities such as rising from a chair or climbing stairs. • Cardiac involvement: Up to 50% of manifesting carriers develop cardiac abnormalities, including dilated cardiomyopathy and arrhythmias. Cardiac symptoms may precede or occur without significant skeletal muscle involvement. • Neurocognitive features: Most carriers have normal cognition, but subtle neurocognitive deficits may occur. • Other: Some may experience unexplained chest or abdominal pain. Symptoms DMD and BMD are X-linked recessive disorders caused by mutations in a gene on the X chromosome that encodes dystrophin, an essential structural protein in muscle. Females have two X chromosomes and are typically unaffected in X-linked disorders, as one X chromosome can compensate for the faulty one, making them“carriers.”Males, with only one X chromosome, are more severely affected due to the absence of a “back-up” X chromosome. It is commonly believed that female carriers of DMD and BMD merely transmit the abnormal dystrophin gene and are not themselves affected. While this is true in most cases, sometimes, due to random chance Above: This photomicrograph revealed histopathologic changes found in a skeletal muscle tissue harvested from the gastrocnemius muscle, of a patient with Duchenne muscular dystrophy (DMD), also known as pseudohypertrophic muscular dystrophy. This cross section of the muscle, shows extensive replacement of muscle fibers, by adipose, or fat cells.