Muscles: Duchenne muscular dystrophy

Dystrophin is an important structural protein in skeletal (striated) muscle. It is located in the cytoplasm, where it helps connect actin filaments in the cytoskeleton of muscle fibers to the extracellular matrix (ECM), as shown in Figure 1. Dystrophin is important for maintaining the mechanical stability of skeletal muscle.

Figure 1 The role of dystrophin in muscle structure and integrity

Duchenne muscular dystrophy (DMD) is a genetic condition caused by a mutation in the gene coding for dystrophin. In DMD, the absence of dystrophin causes muscle cells to be increasingly fragile and prone to membrane damage. The result of this damage is a steady leak of calcium into the sarcolemma, disrupting signaling pathways and ultimately causing mitochondria to burst. Damaged muscle tissue is progressively replaced by scar tissue and fat.

DMD typically presents around the age of three, first presenting as pain and weakness affecting the muscles of the hips, thighs, and shoulders, and then progressing to the arms, legs, and trunk. Other symptoms include awkward gait, frequent falls, fatigue, poor progression of motor skills, and enlargement of the tongue and calf muscles. The average life expectancy of DMD patients is 25 years.

A 26-year-old pregnant woman is concerned about the risk of DMD in her unborn child. She has an eight-year-old nephew who was recently diagnosed with the condition and an uncle who died before she was born and had a “developmental disorder” with symptoms similar to those described in DMD patients. To help assess the risk to her child, her doctor helps the woman develop a family pedigree, as shown in Figure 2.

Figure 2 Pedigree showing DMD cases and carriers in patient’s family