A 3-year-old boy from North India presents with progressive muscle weakness, difficulty climbing stairs, and frequent falls. On examination, he has pseudohypertrophy of the calf muscles, a waddling gait, and positive Gowers' sign. Serum creatine kinase (CK) is markedly elevated at 8,500 IU/L. Genetic testing reveals a deletion in the dystrophin gene on the X chromosome. What is the most likely diagnosis?

Explanation

## Diagnosis: Duchenne Muscular Dystrophy (DMD) **Key Point:** Duchenne muscular dystrophy is an X-linked recessive disorder caused by mutations (most commonly deletions) in the dystrophin gene, resulting in absence or severe deficiency of the dystrophin protein. ### Clinical Features - **Age of onset:** 2–5 years (this patient is 3 years old) - **Gait abnormality:** Waddling gait due to hip girdle weakness - **Gowers' sign:** Patient uses hands to push off thighs to stand (pathognomonic for proximal lower limb weakness) - **Pseudohypertrophy:** Calf muscles appear enlarged but are weak due to fatty infiltration - **Progressive course:** Wheelchair-bound by age 10–12 years - **Cardiac involvement:** Dilated cardiomyopathy (common cause of death) - **Respiratory involvement:** Progressive weakness of respiratory muscles ### Laboratory Findings | Feature | DMD | | --- | --- | | **CK level** | Markedly elevated (5,000–100,000 IU/L) | | **Genetic defect** | Dystrophin gene deletion (60%), duplication (5%), point mutation (35%) | | **Dystrophin protein** | Absent or severely reduced | | **EMG** | Myopathic pattern | | **Muscle biopsy** | Fiber necrosis, regeneration, fatty infiltration; absent dystrophin on immunohistochemistry | **High-Yield:** DMD is the most common muscular dystrophy in children and the most common X-linked recessive disorder in males. Females are carriers; affected males rarely reproduce. ### Differential Diagnosis | Disorder | Key Distinguishing Feature | | --- | --- | | **Becker MD** | Later onset (5–15 yrs), slower progression, milder phenotype; dystrophin present but abnormal | | **Limb-girdle MD** | Autosomal recessive/dominant inheritance; proximal weakness but no pseudohypertrophy | | **SMA** | Autosomal recessive; earlier onset; fasciculations; normal CK; SMN gene mutation | **Clinical Pearl:** The combination of early-onset proximal weakness, pseudohypertrophy of calves, and Gowers' sign in a young boy is virtually pathognomonic for DMD. Markedly elevated CK confirms muscle necrosis. **Mnemonic: DMD = Deletion, Males, Dystrophin absent** — X-linked recessive affecting males with complete loss of dystrophin protein.