31.4 Symptoms of DMD

The symptoms of DMD can be seen in early childhood days (before age 6) and sometimes during infancy. The characteristic symptom of DMD includes delay of motor neuron activity which independently affects sitting and standing ability. Due to delay in achieving control over the muscle movement the child affected with DMD takes longer time to start walking as compared to normal children. The mean age for walking in boys with DMD has been recorded to be about 18 months. Muscle weakness of the legs and pelvis region progresses with age and the loss of muscle mass also known as muscle wasting takes place. The enlargement of calf muscle occurs followed by the replacement of the muscle tissue by fat and connective tissue generally termed as the “pseudohypertrophic condition”. Weakness in the muscle results in a characteristic way of walking called as “waddling gait”. Due to the tightening of tendons around the heels, the person has to walk on tiptoes resulting in “lordosis” (development of forward curvature of the spine). The affected person finds difficulty in walking and climbing stairs. The muscles of the lower half of the body weakens earlier and more severely than the muscles of other parts of the body like the shoulder, arms, neck etc. In the later stages the affected person is unable to walk (gets confined to the wheelchair) followed by “scoliosis” (curvature of spine to the sides) and “contractures” (tightening of joints). In the last stages of the disease weakening of chest muscle and heart muscle takes place resulting in severe respiratory problem. Death takes place due to heart failure (cardiomyopathy) or respiratory failure.

31.5 Diagnosis of DMD

DMD can be diagnosed by the symptoms as well as by measuring the amount of creatinine phosphokinase enzyme level in the blood serum. This enzyme is involved in muscle degeneration and an elevated level of this enzyme (around 20-100 times more than the normal level) is indicative of DMD. Other tests to confirm DMD includes muscle tissue biopsy, electromyography (EMG) and molecular tests.

31.6 The mdx mouse

To understand the underlying mechanism involved in the process of muscle degeneration and regeneration, the animal model being used is the mdx mouse. The dystrophic mdx mouse contains a point mutation that causes a change in the codon in the dystrophin gene resulting in changeover of glutamine amino acid to termination codon (CAA, CAG encodes for glutamine which may be changed by replacement of any of the three letters with T. In case the C in CAA and CAG is replaced by T then it becomes TAA and TAG, which are stop codons and result in premature stop of dystrophin synthesis and formation of non functional dystrophin in the muscle). All experiments related to DMD use the mdx mouse as the animal model. From the beginning, different stages of skeletal muscle degeneration and subsequent regeneration can be observed in the mdx mouse. As the mdx mouse grows old generally the diaphragm muscle weakens followed by development of fibrosis in the muscle.