Duchenne muscular dystrophy (DMD)

Duchenne muscular dystrophy (DMD) is an X linked recessive disorder caused by a mutation in the dystrophin gene characterized by progressive muscular weakness along with fibrosis and fatty replacement; Dystrophin helps to anchor the muscle cytoskeleton to the extracellular matrix.

Presents with muscle weakness, pseudohypertrophy of calf muscles, waddling gait, decreased DTRs and positive Gower's sign; Muscle weakness is manifested as toe walking, difficulty running, climbing up stairs, and frequently falling; Patients are generally wheelchair‐bound by the age of twelve and often succumb to either cardiac or respiratory failure or both by the mid to late twenties; Cardiac failure is due to cardiomyopathy and conduction abnormalities (e.g. SVT); Respiratory failure is due to weakness of intercoastal and diaphragmatic muscles causing respiratory insufficiency.

Gower’s sign:- Patient uses upper extremities to help stand up; as proximal muscles are affected early as compared to distal muscles.

Diagnosis:-
1. Muscle enzymes (e.g. creatine kinase, aldolase, AST) are elevated.
2. Muscle biopsy shows degeneration/regeneration of muscle fibers with fibrofatty replacement.
3. Genetic test shows mutation in dystrophin gene.
4. ECG shows high-voltage R waves in leads V1 and V2 with Q waves in leads I, aVL, and V6 or in leads II, III, and aVF; Associated with conduction abnormalities (e.g. SVT).
5. Echocardiography shows dilated cardiomyopathy at later stages of life.
6. EMG shows myopathy and NCV shows normal.

Treatment:-
1. Supportive measures like diet, exercise and physiotherapy.
2. Steroids (e.g. prednisolone) improves muscle strength and prolongs ambulation.
3. Cardiomyopathy is treated with ACEi, beta blockers, diuretics and digoxin.
4. Eteplirsen (Exon 51 skipping antisense oligonucleotide).