Overview
Clinical Pattern and Mechanism
Duchenne muscular dystrophy (DMD) is caused by a pathogenic variant in the X linked DMD gene that eliminates or severely reduces dystrophin.
Duchenne muscular dystrophy (DMD) is caused by a pathogenic variant in the X-linked DMD gene that eliminates or severely reduces dystrophin. Dystrophin normally helps anchor the muscle cell’s internal actin framework to the extracellular matrix. Without that structural support, repeated contraction makes the sarcolemma fragile. Calcium enters injured muscle fibres, activates destructive enzymes, and promotes inflammation, necrosis, fibrosis, and fatty replacement. The result is progressive loss of functional muscle rather than simple deconditioning. Weakness is most noticeable proximally: the hips, thighs, shoulders, and trunk are affected before the hands and feet. A young child may have delayed motor milestones, difficulty running or climbing stairs, frequent falls, a waddling gait, or trouble rising from the floor. The child may push the hands against the thighs to stand—the Gowers manoeuvre. Enlarged calves can reflect fatty and fibrous replacement rather than increased strength. DMD primarily affects males because of its X-linked inheritance, although females may have clinically significant disease and require assessment when symptoms and genetic findings support it. Respiratory muscles and cardiac muscle are also dystrophin-deficient. A child who still walks and...